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Sample records for atypical antipsychotic drug

  1. Therapeutic drug monitoring of atypical antipsychotic drugs

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    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  2. Atypicality of Atypical Antipsychotics

    OpenAIRE

    Farah, Andrew

    2005-01-01

    Objective: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality.

  3. Atypical antipsychotics and glucose homeostasis.

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    Bergman, Richard N; Ader, Marilyn

    2005-04-01

    needed. A major problem in assessing drug effects is that psychiatric disease itself can cause many of the manifestations leading to diabetes, including weight gain and sedentary lifestyle. While studies in healthy subjects are limited and inconclusive, studies in animal models are more revealing. In the conscious canine model, some atypical antipsychotics cause adiposity, including visceral obesity, a strong risk factor for the metabolic syndrome. Furthermore, while few studies have examined effects of antipsychotics on pancreatic beta-cell function, canine studies demonstrate that expected beta-cell compensation for insulin resistance may be reduced or even eliminated with these agents. Atypical antipsychotics have been shown to contribute to weight gain, which may well reflect increased body fat deposition. Such increased fat is known to cause resistance to insulin action, although more information regarding effect on insulin action is needed. The effect of these drugs on fat distribution has been clearly shown in animal models. It is known that the normal response to insulin resistance is compensatory hyperinsulinemia, which may prevent diabetes. In animals, there is evidence that the hyperinsulinemic compensation is inadequate in the face of atypical antipsychotic agents. It remains to be examined whether failure of adequate pancreatic beta-cell compensation for insulin resistance plays a central role in the pathogenesis of diabetes associated with this class of drugs.

  4. ATYPICAL ANTIPSYCHOTICS USE IN CHILDREN AND ADOLESCENTS

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    Nataša Potočnik-Dajčman

    2002-06-01

    Full Text Available Background. Classical antipsychotics – neuroleptics are one of the most frequently prescribed psychotropic drugs in child psychiatry. Atypical antipsychotics are used for the same indications – psychotic (schizophrenia as well as unpsychotic disorders (pervasive developmental disorders, mood disorders, conduct disorders and tics disorders. It is surprising that the studies on their use with regard to this age group are rather rare. They are carried out on a small number of samples and only exceptionally double blind. This article summarizes published clinical experience with atypical antipsychotics in children and adolescents. A short overview of pharmacodynamics, pharmacokinetics and side effects is given. Schizophrenia and pervasive developmental disorders are major indications for use of atypical antipsychotics in children and adolescents, but they have also been successfully used for other disorders such as aggressive behaviour, tics and anorexia nervosa.Conclusions. With better side-effect profile, some of the atypical antipsychotics are expected to be doctrinally recognised as the first-line treatment for childhood schizophrenia and pervasive developmental disorders. However, more long-term studies carried out on a larger sample are needed. Atypical antipsychotics are already used in everyday practice as first-line treatment of childhood and adolescents schizophrenia.

  5. The influence of atypical antipsychotic drugs on sexual function

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    Just MJ

    2015-07-01

    Full Text Available Marek J Just Department of General and Endocrine Surgery, Piekary Medical Centre, Piekary Slaskie, Poland Abstract: Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido, physiological arousal (lubrication/erection, orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic. Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. Keywords: schizophrenia, galactorrhea, hyperprolactinemia, mood disorders, anorgasmia

  6. Diabetic ketoacidosis associated with atypical antipsychotic drug, clozapine treatment: Report of a case and review of literature

    OpenAIRE

    Pillai L; Husainy SMK; Ramchandani K

    2006-01-01

    Atypical antipsychotic drugs are associated with metabolic disturbances like weight gain, type 2 diabetes hyperglycaemia and dyslipedemia, which can result in serious health risk in patients. Diabetic ketoacidosis resulting in serious metabolic acidosis, occurring in a schizophrenic patient on treatment with clozapine is being reported to draw attention this association. Frequent monitoring of the blood sugar and lipids is advised before and during therapy with atypical antipsychotic drugs.

  7. Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

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    Sarkar, Siddharth; Gupta, Nitin

    2017-08-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

  8. Atypical antipsychotics: trends in analysis and sample preparation of various biological samples.

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    Fragou, Domniki; Dotsika, Spyridoula; Sarafidou, Parthena; Samanidou, Victoria; Njau, Samuel; Kovatsi, Leda

    2012-05-01

    Atypical antipsychotics are increasingly popular and increasingly prescribed. In some countries, they can even be obtained over-the-counter, without a prescription, making their abuse quite easy. Although atypical antipsychotics are thought to be safer than typical antipsychotics, they still have severe side effects. Intoxications are not rare and some of them have a fatal outcome. Drug interactions involving atypical antipsychotics complicate patient management in clinical settings and the determination of the cause of death in fatalities. In view of the above, analytical strategies that can efficiently isolate atypical antipsychotics from a variety of biological samples and quantify them accurately, sensitively and reliably, are of utmost importance both for the clinical, as well as for the forensic toxicologist. In this review, we will present and discuss novel analytical strategies that have been developed from 2004 to the present day for the determination of atypical antipsychotics in various biological samples.

  9. Animal behavior models of the mechanisms underlying antipsychotic atypicality.

    NARCIS (Netherlands)

    Geyer, M.A.; Ellenbroek, B.A.

    2003-01-01

    This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic

  10. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

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    Moore R Andrew

    2007-08-01

    were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence. Conclusion Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine. There is insufficient data confidently to distinguish between different atypical antipsychotics.

  11. No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

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    Goto, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Moriya, Junji; Hori, Hikaru; Hayashi, Kenji; Ikenouchi-Sugita, Atsuko; Nakano-Umene, Wakako; Katsuki, Asuka; Nishimura, Joji; Korogi, Yukunori; Nakamura, Jun

    2010-12-01

    We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Atypical Antipsychotic Medications and Hyponatremia in Older Adults: A Population-Based Cohort Study

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    Sonja Gandhi

    2016-04-01

    Full Text Available Background: A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. Objective: The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. Design: The design of this study was a retrospective, population-based cohort study. Setting: The setting of this study was in Ontario, Canada, from 2003 to 2012. Patients: Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. Measurements: The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. Methods: Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group. We used conditional logistic regression to compare outcomes among the matched users and non-users. Results: A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 % versus 53/58,008 (0.09 %; relative risk 1.62 (95 % confidence interval (CI 1.15 to 2.29; absolute risk increase 0.06 % (95 % CI 0.02 to 0.10. The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical

  13. Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration Adverse Event database: a systematic Bayesian signal detection analysis.

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    Baker, Ross A; Pikalov, Andrei; Tran, Quynh-Van; Kremenets, Tatyana; Arani, Ramin B; Doraiswamy, P Murali

    2009-01-01

    Prior literature suggests that the risk of diabetes-related adverse events (DRAEs) differs between atypical antipsychotics. The present study evaluated the potential association between atypical antipsychotics or haloperidol and diabetes using data from the FDA AERS database. Analysis of AERS data was conducted for clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole or haloperidol with 24 DRAEs from the Medical Dictionary for Regulatory Activities using a Multi-item Gamma Poisson Shrinker (MGPS) data-mining algorithm. Using MGPS, adjusted reporting ratios (Empiric Bayes Geometric Mean or EBGM) and 90% confidence intervals (CIs; EB05-EB95) were calculated to estimate the degree of drug-event association relative to all drugs and events. Logistic regression odds ratios and 90% CIs (LR05-LR95) were calculated for diabetes mellitus events. All six atypicals had an EB05 >/= 2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2-10.0; 1306 cases); risperidone 3.8 (3.5-4.1; 447 cases); quetiapine 3.5 (3.2-3.9; 283 cases); clozapine 3.1 (2.9-3.3; 464 cases); ziprasidone 2.4 (2.0-2.9; 74 cases); aripiprazole 2.4 (1.9-2.9; 71 cases); haloperidol 2.0 (1.7-2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios. In the AERS database, lower associations with DRAEs were seen for haloperidol, aripiprazole and ziprasidone, and higher associations were seen for olanzapine, risperidone, clozapine and quetiapine. Our findings support differential risk of diabetes across atypical antipsychotics, reinforcing the need for metabolic monitoring of patients taking antipsychotics.

  14. Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

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    Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

    2015-02-01

    To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  15. Effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care.

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    Stargardt, Tom; Weinbrenner, Susanne; Busse, Reinhard; Juckel, Georg; Gericke, Christian A

    2008-06-01

    In two recent randomised clinical trials, a meta-analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs, concerning both their efficacy and their side-effect profile, has been questioned. To analyse the effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care. Cohort study using routine care data from a statutory sickness fund with 5.4 million insured in Germany. To be included, patients had to be discharged with a diagnosis of schizophrenia in 2003 and fulfil membership criteria. Main outcome measures were rehospitalisation rates, mean hospital bed days, mean length of stay, cost of inpatient and pharmaceutical care to the sickness fund during follow-up and medication used to treat side-effects. 3121 patients were included into the study. There were no statistically significant differences in the effectiveness of atypical and typical antipsychotics on rehospitalisation during follow-up (rehospitalisation rate ratio 1.07, 95% confidence interval 0.86 to 1.33). However, there were consistent observations of atypical antipsychotics being more effective for severe cases of schizophrenia (14.6% of study population; >61 prior bed days per year in 2000-2002) in the follow-up period, whereas for the other severity strata typical antipsychotics seemed more effective in reducing various rehospitalisation outcomes. Patients treated with atypical antipsychotics received significantly less prescriptions for anticholinergics or tiaprid (relative risk 0.26, 95% confidence interval 0.18 to 0.38). The effectiveness of atypical antipsychotics for schizophrenia on rehospitalisation measures appeared similar to that of typical antipsychotics. With the exception of severe cases, the higher costs for atypical antipsychotics were not offset by savings from reduced inpatient care. Major limitations include the lack of

  16. Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

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    Maher, Alicia R; Theodore, George

    2012-06-01

    Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including

  17. The effects of antipsychotic drugs on depression level in patients with schizophrenia: clozapine vs. other atypical antipsychotics

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    Hülya Ertekin

    2016-08-01

    Full Text Available Introduction: Depressive symptoms may occur in all stages of schizophrenia disorder. Clozapine is the only antipsychotic that has been demonstrated superior efficacy in schizophrenia and suicidal ideation. The aim of this study is to evaluate depressive symptoms in patients with schizophrenia treated with clozapine and to compare with treated with other atypical antipsychotics.Methods: A cross-sectional descriptive study was carried out on patients with schizophrenia according to DSM-IV-TR between December 2012 and May 2013. All participants were evaluated for demographic characteristics and points of Brief Psychiatric Rating Scale, Positive, Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia.Results: A total 23.6% (n = 13 patients treated with clozapine, while 76.4% (n = 42 patients were treated with other antipsychotic drugs. 23.1% (n = 3 of patients taking clozapine were women, 76.9% (n = 10 were male. The mean age of patients treated with clozapine was 43.0 ± 11.2. The level of depression of patients treated with clozapine was 15.4% (n = 2. No statistically significant difference was found between patients between treated with clozapine and other antipsychotics regarding age, sex, marital status, education years, work history, age at onset of disease, depression and history of suicide attemptConclusion: As a result of this study it is found that clozapine did not effect on the level of depression in patients with schizophrenia, and depression level of patients with schizophrenia treated with clozapine had no difference from  patients treated  with other antipsychotics.

  18. Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality.

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    Heresco-Levy, Uriel

    2003-10-01

    The neurotransmission mediated by the excitatory amino acids (EAA) glutamate (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its role in neurodevelopment and neurotoxicity, its complex interactions with dopaminergic and other neurotransmitter systems and its pivotal importance in recent models of schizophrenia. Accumulating evidence indicates that modulation of glutamatergic neurotransmission may play an important role in the mechanisms of action of atypical antipsychotic drugs. The principles of the phencyclidine (PCP) model of schizophrenia suggest that conventional neuroleptics cannot counteract all aspects of schizophrenia symptomatology, while a more favorable outcome, including anti-negative and cognitive symptoms effects, would be expected with the use of treatment modalities targeting glutamatergic neurotransmission. Clozapine and other presently used atypical antipsychotics differ from conventional neuroleptics in the way they affect various aspects of glutamatergic receptors function. In this context, a specific hypothesis suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA) subtype of GLU receptors has been postulated. Furthermore, the results of the first generation of clinical trials with glycine (GLY) site agonists of the NMDA receptor in schizophrenia suggest that this type of compounds (1) have efficacy and side effects profiles different than those of conventional neuroleptics and (2) differ in their synergic effects when used in addition to conventional neuroleptics versus clozapine and possibly additional atypical antipsychotics. These findings (1) bring further support to the hypothesis that glutamatergic effects may play an important role in the mechanism of action of atypical antipsychotics, (2) help explain the unique clinical profile of clozapine, and (3) suggest that GLY site agonists of the NMDA receptor may represent a new class of atypical antipsychotic medication. Future research in

  19. State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics.

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    Möller, H J

    2000-10-01

    Neuroleptic medication is the most important part of the treatment regimen for schizophrenic patients. The efficacy of neuroleptics in the acute and long-term treatment of schizophrenia is very well proven and the effect size is comparatively high. After more than 40 years of clinical practice with the classical neuroleptics, several more or less generally accepted rules for the management of drug treatment in schizophrenia have been established. The paper aims to describe these standards, discussing, among other things, developments which have appeared in the last 10 to 20 years, e.g. the tendency to a lower daily dose during acute treatment and the tendency to alternative strategies during long-term treatment. The paper especially also takes into consideration the benefits of the novel/atypical antipsychotics as compared to the classical neuroleptics, which will change the current treatment standards under several aspects--a change which is already ongoing. The novel/atypical antipsychotics will be much better accepted by patients, thus leading to increased compliance, will be associated with a better quality of life and will possibly change the long-term outcome of schizophrenic patients in a very important manner. It should be considered that the so-called novel/atypical neuroleptics do not constitute a homogeneous group but are a group of individual drugs, each with their own advantages and disadvantages. As was the situation with the classical neuroleptics, the physician also has to choose the most adequate drug under consideration of the risk/benefit profile of each drug in relation to the disposition of the individual patient.

  20. Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

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    Correll Christoph

    2005-05-01

    Full Text Available Abstract Background Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. Methods Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796 who were initiated during the study on olanzapine (N = 405, quetiapine (N = 115, or risperidone (N = 276. The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. Results During the 1-year period, only a third (35.7% of the patients were treated predominately with monotherapy (>300 days. Most patients (57.7% had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days. Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043 or quetiapine (p = .002. The number of monotherapy days was significantly greater for olanzapine than quetiapine (p Conclusion Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic

  1. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

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    Tomiki eSumiyoshi

    2013-10-01

    Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  2. Generic penetration in the retail atypical antipsychotic market.

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    Lenderts, Susan; Kalali, Amir H; Buckley, Peter

    2010-03-01

    In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

  3. DISRUPTION OF CONDITIONED REWARD ASSOCIATION BY TYPICAL AND ATYPICAL ANTIPSYCHOTICS

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    Danna, C.L.; Elmer, G.I.

    2013-01-01

    Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100 μg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3–30 μg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward

  4. Stimulant and atypical antipsychotic medications for children placed in foster homes.

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    L Oriana Linares

    Full Text Available The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time.The sample included N = 252 children (nested in 95 sibling groups followed for three years up to 4 yearly waves.Nearly all (89% met criteria for at least one of eight psychiatric diagnoses and 31% (75/252 used one or more prescribed psychoactive medications. Over half (55% were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD; of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ≥3 different classes of drugs over the course of the study. Stimulants (69% and atypical antipsychotics (65% were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR showed that male gender (AOR = 3.2; 95% CI = 1.5-9.3, African American vs Latino ethnicity (AOR = 5.4; 95% CI = 2.1-14.2, ADHD regardless of Oppositional Defiant (ODD or Conduct (CD comorbidity (AOR = 6.0, 95% CI = 1.3-27.5, ODD or CD (AOR = 11.1, 95% CI = 2.1-58.6, and Separation Anxiety (AOR = 2.0, 95% CI = 1.0-4.0 psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR = 3.8, 95% CI = 1.5-9.3, African American vs Latino (AOR = 5.1, 95% CI = 1.2-9.2 or Mixed/Other ethnicity (AOR = 3.3, 95% CI = 1.9-13.7, ADHD regardless of ODD or CD comorbidity (AOR = 5.8, 95% CI = 1.2-28.7, ODD or CD (AOR = 13.9, 95% CI = 3.3-58.5, Major Depression/Dysthymia (AOR = 2.8, 95% CI = 1.1-6.7 psychiatric disorders, and history of sexual abuse (AOR = 4.6, 95% CI = 1.3-18.4 were associated with the use of

  5. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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    Kjell A Svensson

    2012-05-01

    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  6. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Zuardi A.W.

    2006-01-01

    Full Text Available A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD, a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

  7. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu

    2011-03-01

    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  8. The role of atypical antipsychotics for treatment of Tourette's syndrome: an overview.

    Science.gov (United States)

    Budman, Cathy L

    2014-07-01

    Tourette's syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by multiple motor and phonic tics that fluctuate over time. Tic symptoms often improve by late adolescence, but some children and adults with TS may experience significant tic-related morbidity, including social and family problems, academic difficulties, and pain. When more conservative interventions are not successful, and when certain psychiatric co-morbidities further complicate the clinical profile, treating TS with an atypical antipsychotic medication may be a reasonable second-tier approach. However, the evidence supporting efficacy and safety of the atypical antipsychotics for treatment of tics is still very limited. The objective of this paper is to provide an updated overview of the role of atypical antipsychotics for treatment of TS, with evidence-based guidance on their use. Evidence for efficacy of different typical and atypical antipsychotics for treatment of tics was examined by conducting a systematic, keyword-related search of 'atypical antipsychotics' and 'Tourette's syndrome' in PubMed (National Library of Medicine, Washington, DC, USA). Four recent treatment consensus publications were also reviewed. This review focused on literature published from 2000 to 2013 and on available randomized controlled trials in TS. Evidence supporting the use of atypical antipsychotics for treatment of TS is limited. There are few randomized medication treatment trials in TS (i.e. risperidone, aripiprazole, ziprasidone), which employed varying methodologies, thereby restricting meaningful comparisons among studies. Future collaborations among clinical sites with TS expertise employing high-quality study design may better elucidate the role of atypical antipsychotics for treatment of TS.

  9. Stimulant and Atypical Antipsychotic Medications For Children Placed in Foster Homes

    Science.gov (United States)

    Linares, L. Oriana; Martinez-Martin, Nuria; Castellanos, F. Xavier

    2013-01-01

    Objectives The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time. Methods The sample included N = 252 children (nested in 95 sibling groups) followed for three years up to 4 yearly waves. Results Nearly all (89%) met criteria for at least one of eight psychiatric diagnoses and 31% (75/252) used one or more prescribed psychoactive medications. Over half (55%) were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD); of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ≥3 different classes of drugs over the course of the study. Stimulants (69%) and atypical antipsychotics (65%) were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR) showed that male gender (AOR = 3.2; 95% CI = 1.5–9.3), African American vs Latino ethnicity (AOR = 5.4; 95% CI = 2.1–14.2), ADHD regardless of Oppositional Defiant (ODD) or Conduct (CD) comorbidity (AOR = 6.0, 95% CI = 1.3–27.5), ODD or CD (AOR = 11.1, 95% CI = 2.1–58.6), and Separation Anxiety (AOR = 2.0, 95% CI = 1.0–4.0) psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR = 3.8, 95% CI = 1.5–9.3), African American vs Latino (AOR = 5.1, 95% CI = 1.2–9.2) or Mixed/Other ethnicity (AOR = 3.3, 95% CI = 1.9–13.7), ADHD regardless of ODD or CD comorbidity (AOR = 5.8, 95% CI = 1.2–28.7), ODD or CD (AOR = 13.9, 95% CI = 3.3–58.5), Major Depression/Dysthymia (AOR = 2.8, 95% CI = 1.1–6.7) psychiatric disorders, and history of sexual abuse (AOR = 4.6, 95

  10. Increasing use of atypical antipsychotics and anticonvulsants during pregnancy

    Science.gov (United States)

    Epstein, Richard A.; Bobo, William V.; Shelton, Richard C.; Arbogast, Patrick G.; Morrow, James A.; Wang, Wei; Chandrasekhar, Rameela; Cooper, William O.

    2013-01-01

    Purpose To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants and lithium during pregnancy. Methods Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. Results During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1,000 pregnancies (β = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. Conclusions There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted. PMID:23124892

  11. Aripiprazole versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; El-Sayeh, Hany George G; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of other second generation antipsychotics. Objectives To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side

  12. Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

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    Eduardo Henrique Teixeira

    2013-01-01

    Full Text Available Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA. All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.

  13. Self-limiting atypical antipsychotics-induced edema: Clinical cases and systematic review

    OpenAIRE

    Musa Usman Umar; Aminu Taura Abdullahi

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

  14. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

    Science.gov (United States)

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

  15. Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.

    Science.gov (United States)

    Epstein, Richard A; Bobo, William V; Shelton, Richard C; Arbogast, Patrick G; Morrow, James A; Wang, Wei; Chandrasekhar, Rameela; Cooper, William O

    2013-07-01

    To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants, and lithium during pregnancy. Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1000 pregnancies (β = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

    Science.gov (United States)

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

  17. Minimizing Cardiovascular Adverse Effects of Atypical Antipsychotic Drugs in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Fadi T. Khasawneh

    2014-01-01

    Full Text Available The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients.

  18. Current status of atypical antipsychotics for the treatment of fibromyalgia.

    Science.gov (United States)

    Rico-Villademoros, F; Calandre, E P; Slim, M

    2014-06-01

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.

  19. The effects of typical and atypical antipsychotics on the electrical activity of the brain in a rat model

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    Oytun Erbaş

    2013-09-01

    Full Text Available Objective: Antipsychotic drugs are known to have strongeffect on the bioelectric activity in the brain. However,some studies addressing the changes on electroencephalography(EEG caused by typical and atypical antipsychoticdrugs are conflicting. We aimed to compare the effectsof typical and atypical antipsychotics on the electricalactivity in the brain via EEG recordings in a rat model.Methods: Thirty-two Sprague Dawley adult male ratswere used in the study. The rats were divided into fivegroups, randomly (n=7, for each group. The first groupwas used as control group and administered 1 ml/kg salineintraperitoneally (IP. Haloperidol (1 mg/kg (group 2,chlorpromazine (5 mg/kg (group 3, olanzapine (1 mg/kg(group 4, ziprasidone (1 mg/ kg (group 5 were injectedIP for five consecutive days. Then, EEG recordings ofeach group were taken for 30 minutes.Results: The percentages of delta and theta waves inhaloperidol, chlorpromazine, olanzapine and ziprasidonegroups were found to have a highly significant differencecompared with the saline administration group (p<0.001.The theta waves in the olanzapine and ziprasidonegroups were increased compared with haloperidol andchlorpromazine groups (p<0.05.Conclusion: The typical and atypical antipsychotic drugsmay be risk factor for EEG abnormalities. This studyshows that antipsychotic drugs should be used with caution.J Clin Exp Invest 2013; 4 (3: 279-284Key words: Haloperidol, chlorpromazine, olanzapine,ziprasidone, EEG, rat

  20. Correlation between plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia.

    Science.gov (United States)

    Kaneda, Yasuhiro; Kawamura, Ichiro; Ohmori, Tetsuro

    2005-01-01

    The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.

  1. Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Swartz Marvin

    2006-02-01

    Full Text Available Abstract Background There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia. Methods We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone or oral typical antipsychotics (low, medium, or high potency were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods. To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a only 1 medication episode for each patient, the one with which the patient was treated first, and (b all medication episodes, including those simultaneously initiated on more than 1 antipsychotic. Results Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days compared to typical antipsychotics (N = 534, 197.2 days; p Conclusion In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium

  2. A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

    Science.gov (United States)

    López-Muñoz, Francisco; De Berardis, Domenico; Fornaro, Michele; Vellante, Federica; di Giannantonio, Massimo; Povedano-Montero, Francisco J; Póveda Fernández-Martín, Maria; Rubio, Gabriel; Álamo, Cecilio

    2017-01-01

    A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

  3. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.

    Science.gov (United States)

    Meltzer, H Y; Matsubara, S; Lee, J C

    1989-10-01

    The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics.

    Science.gov (United States)

    Li, Xiaohua; Rosborough, Kelley M; Friedman, Ari B; Zhu, Wawa; Roth, Kevin A

    2007-02-01

    Glycogen synthase kinase-3 (GSK3) has been recognized as an important enzyme that modulates many aspects of neuronal function. Accumulating evidence implicates abnormal activity of GSK3 in mood disorders and schizophrenia, and GSK3 is a potential protein kinase target for psychotropics used in these disorders. We previously reported that serotonin, a major neurotransmitter involved in mood disorders, regulates GSK3 by acutely increasing its N-terminal serine phosphorylation. The present study was undertaken to further determine if atypical antipsychotics, which have therapeutic effects in both mood disorders and schizophrenia, can regulate phospho-Ser-GSK3 and inhibit its activity. The results showed that acute treatment of mice with risperidone rapidly increased the level of brain phospho-Ser-GSK3 in the cortex, hippocampus, striatum, and cerebellum in a dose-dependent manner. Regulation of phospho-Ser-GSK3 was a shared effect among several atypical antipsychotics, including olanzapine, clozapine, quetiapine, and ziprasidone. In addition, combination treatment of mice with risperidone and a monoamine reuptake inhibitor antidepressant imipramine or fluoxetine elicited larger increases in brain phospho-Ser-GSK3 than each agent alone. Taken together, these results provide new information suggesting that atypical antipsychotics, in addition to mood stabilizers and antidepressants, can inhibit the activity of GSK3. These findings may support the pharmacological mechanisms of atypical antipsychotics in the treatment of mood disorders.

  5. Application of an empiric Bayesian data mining algorithm to reports of pancreatitis associated with atypical antipsychotics.

    Science.gov (United States)

    Hauben, Manfred

    2004-09-01

    To compare the results from one frequently cited data mining algorithm with those from a study, which was published in a peer-reviewed journal, that examined the association of pancreatitis with selected atypical antipsychotics observed by traditional rule-based methods of signal detection. Retrospective pharmacovigilance study. The widely studied data mining algorithm known as the Multi-item Gamma Poisson Shrinker (MGPS) was applied to adverse-event reports from the United States Food and Drug Administration's Adverse Event Reporting System database through the first quarter of 2003 for clozapine, olanzapine, and risperidone to determine if a significant signal of pancreatitis would have been generated by this method in advance of their review or the addition of these events to the respective product labels. Data mining was performed by using nine preferred terms relevant to drug-induced pancreatitis from the Medical Dictionary for Regulatory Activities (MedDRA). Results from a previous study on the antipsychotics were reviewed and analyzed. Physicians' Desk References (PDRs) starting from 1994 were manually reviewed to determine the first year that pancreatitis was listed as an adverse event in the product label for each antipsychotic. This information was used as a surrogate marker of the timing of initial signal detection by traditional criteria. Pancreatitis was listed as an adverse event in a PDR for all three atypical antipsychotics. Despite the presence of up to 88 reports/drug-event combination in the Food and Drug Administration's Adverse Event Reporting System database, the MGPS failed to generate a signal of disproportional reporting of pancreatitis associated with the three antipsychotics despite the signaling of these drug-event combinations by traditional rule-based methods, as reflected in product labeling and/or the literature. These discordant findings illustrate key principles in the application of data mining algorithms to drug safety

  6. The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia

    Directory of Open Access Journals (Sweden)

    Sánchez-Moreno José

    2010-06-01

    Full Text Available Abstract Background Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs on cognitive performance over time. Methods In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13 or novel antipsychotics (n = 26 at baseline and at two years after. Results Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

  7. Atypical antipsychotic usage among Asian Americans and Pacific Islanders.

    Science.gov (United States)

    Takeshita, Junji; Goebert, Deborah; Else, Iwalani; Carlton, Barry; Matsu, Courtenay; Guerrero, Anthony

    2014-09-01

    Previous studies have shown significant ethnic differences in prescribing patterns of two or more antipsychotics. This study examined changes in atypical and typical antipsychotic prescriptions among Asian Americans and Pacific Islanders. Five hundred consecutive charts were reviewed for antipsychotics at the time of admission and discharge from each of two inpatient psychiatric facilities in Hawai'i. Multiple antipsychotic prescription rates were 9% at intake and 6% at discharge. For the ethnic groups studied, there were no statistically significant differences by patient ethnicity regarding antipsychotics at intake (χ(2) = 29.2, df = 21, P = .110) or discharge (χ(2) = 20.5, df = 24, P = .667). There were no significant differences in prescription and polypharmacy patterns among Asian Americans and Pacific Islanders ethnic groups in this study.

  8. Association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use

    International Nuclear Information System (INIS)

    Ikram, H.; Ahmed, T.M.; Hayat, A.; Ullah, Q.I.; Nawaz, A.

    2017-01-01

    Objective: To determine the association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use. Study Design: Case control study. Place and Duration of Study: Chemical pathology department Army Medical College Rawalpindi, from Nov 2014 to Oct 2015. Material and Methods: The study was carried out on 240 subjects, 120 cases and 120 controls. For the purpose of the study cases were divided into four groups A, B, C and D according to the duration of drug use. Group A patients included those who the last the drug olanzapine for the last three months. Group B patients included those who were using the drug olanzapine for the last six months. Group C and D included those who were using the drug for last 1 year and more than one year (2-5 years) respectively. By employing non probability convenience sampling technique the data was collected from patients having the diagnosis of psychosis as per DSM IV modified criteria through a proforma and fasting blood samples were drawn. These samples were tested for fasting serum lipid profile and fasting plasma glucose. The data obtained were analyzed using SPSS version 21. For quantitative data Mean and SD were calculated. For qualitative data frequency and percentages were calculated. Qualitative data was compared using chi square test whereas quantitative data was compared using independent sample t-test. Results: There was statistically no significant difference in fasting plasma glucose between group A and B and their controls whereas in group C and D these levels were significantly high as compared to controls. Triglyceride levels were significantly higher and HDL cholesterol levels were significantly lower in all four groups as compared to controls. Comparison of qualitative data which included waist circumference and blood pressure showed statistically no significant rise for group A whereas waist circumference showed insignificant rise and blood pressure showed statistically

  9. Trends in the Outpatient Utilization of Antipsychotic Drugs in the City of Zagreb in the Ten-Year Period as a Tool to Assess Drug Prescribing Rationality.

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    Polić-Vižintin, Marina; Tripković, Ingrid; Štimac, Danijela; Šostar, Zvonimir; Orban, Mirjana

    2016-12-01

    The aim was to determine distribution and trends in the outpatient utilization of antipsychotics to evaluate the rationality of antipsychotic drug prescribing during the ten year period. The epidemiological method of descriptive and analytical observation was used. Data on drug utilization from Zagreb Municipal Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the World Health Organization Anatomical-Therapeutic-Chemical methodology. The ratio of typical versus atypical antipsychotics served as an indicator on assessing the rationality of the utilization. Data on the use of anticholinergics in the treatment of neuroleptic side effects were also included. Outpatient utilization of antipsychotics showed a declining pattern from 14.17 in 2001 to 8.42 DDD/TID in 2010. The utilization of atypical antipsychotics increased by 60% (from 3.68 to 5.89 DDD/TID), while the utilization of typical antipsychotics decreased by 76% (from 10.49 to 2.53 DDD/TID). The drugs showing the largest increase were olanzapine (from 1.21 to 2.78 DDD/TID) and quetiapine (from 0 to 0.68 DDD/TID). The typical/atypical antipsychotic ratio changed from 1:0.4 in 2001 to 1:2.3 in 2010. A 2.3-fold decrease was recorded in the utilization of anticholinergics (from 2.05 to 0.91 DDD/TID). Total consumption of neuroleptics significantly decreased. A decrease was also recorded in the utilization of anticholinergics. Study results pointed to two favorable features, i.e. low use of typical antipsychotics and the ratio of typical and atypical antipsychotics. Implementation of the new clinical guidelines for nervous system disorders and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in the prescribing patterns during the study period. Using the WHO ATC/DDD methodology and rationality indicators in the assessment of trends in the outpatient utilization of

  10. Amisulpride versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50

  11. Cognitive Function and Depression in Symptom Resolution in Schizophrenia Patients Treated with an Atypical Antipsychotic

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    Stip, Emmanuel; Mancini-Marie, Adham

    2004-01-01

    Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…

  12. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

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    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  13. Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

    Science.gov (United States)

    Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P

    2007-02-01

    Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.

  14. Metabolic syndrome and psychiatrists' choice of follow-up interventions in patients treated with atypical antipsychotics in Denmark and Sweden

    DEFF Research Database (Denmark)

    Larsen, J. T.; Fagerquist, M.; Holdrup, M.

    2011-01-01

    rate of metabolic syndrome did not elicit much decisive action on the part of the treating psychiatrists; the most frequent action taken was dietary and exercise advice (in 75% of subjects), while in 54% and 19% of subjects a laboratory follow-up and blood pressure follow-up were advised respectively......Introduction: The aim of the present study was to obtain point prevalence estimates of the metabolic syndrome according to the NCEP III criteria in a sample of patients with schizophrenia spectrum disorders treated with atypical antipsychotic drugs in Denmark and Sweden, and to assess...... for at least 3 months with atypical antipsychotic drugs. Results: The metabolic syndrome as per medical history was present in 1% of 582 evaluable patients at baseline. After performing laboratory measurements and applying the NCEP III criteria, metabolic syndrome was confirmed in 43% of subjects. The high...

  15. Adverse drug reactions due to antipsychotics and sedative-hypnotics in the elderly

    Directory of Open Access Journals (Sweden)

    Natasha S Kate

    2015-01-01

    Full Text Available Psychotropic drugs are commonly used to manage mental and behavioral problems in geriatric patients. This is, however, accompanied by the risk of developing adverse drug reactions (ADRs, impacting the safety with which the drug can be used. In this article, we provide an overview of the factors associated with the ADRs due to psychotropic medication in the elderly, and the ADRs associated with the use of antipsychotics and sedative-hypnotics in the geriatric population. For this, literature searches were conducted through MEDLINE, PubMed, and Google Scholar using keyword terms: Geriatric, elderly, safety, adverse events, ADRs, antipsychotic, names of individual antipsychotics, benzodiazepine, sedative, hypnotic, zolpidem, zaleplon, zopiclone. Research data indicate that antipsychotics are associated with an increased risk of metabolic syndrome, thromboembolism, cerebrovascular and cardiac events, pneumonia, fractures, and increased mortality. Among antipsychotics, aripiprazole seems to have fewer ADRs while other antipsychotics (typical and atypicals have reports of troublesome side effect profiles. Sedative-hypnotics are associated with a risk of falls, fractures, cognitive impairment, and may increase the risk of developing dementia with long-term use. The risk of these complications is present with both benzodiazepines and medications such as zolpidem and zopiclone.

  16. Antipsychotics and associated risk of out-of-hospital cardiac arrest.

    Science.gov (United States)

    Weeke, P; Jensen, A; Folke, F; Gislason, G H; Olesen, J B; Fosbøl, E L; Wissenberg, M; Lippert, F K; Christensen, E F; Nielsen, S L; Holm, E; Kanters, J K; Poulsen, H E; Køber, L; Torp-Pedersen, C

    2014-10-01

    Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of the event. Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30).

  17. [From cradle to grave? Expectations from atypical antipsychotics].

    Science.gov (United States)

    Frecska, Ede

    2005-03-01

    Clinical expectations are high toward atypical, second generation antipsychotics (SGAs). Controlled clinical trials supporting the superiority of SGAs over traditional agents are scarce. Meta-analysis of existing data may come for the rescue but that kind of method has its limitations. One of the most meticulous approaches (Davis et al. 2003) reached the conclusion that some, but not all, SGAs are more efficacious than traditional ones. Within the group of distinguished drugs, clozapine and amisulpride have the highest efficacy. The present paper critically overviews the study of the Davis group. Based on in vivo D2 receptor binding data of the new SGAs and the usual post marketing changes of clinical dosing, it is expected that some of the currently and most recently marketed SGAs may show similar superiority.

  18. Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study.

    Science.gov (United States)

    Peng, Mei; Gao, Keming; Ding, Yiling; Ou, Jianjun; Calabrese, Joseph R; Wu, Renrong; Zhao, Jingping

    2013-08-01

    This study aims to investigate the developmental effects of atypical antipsychotics on infants who were born to mothers taking an atypical antipsychotic throughout pregnancy. The developmental progress of 76 infants who experienced fetal exposure to atypical antipsychotics was compared to that of 76 matched control infants who had no fetal exposure to any antipsychotics. Planned assessment included Apgar score, body weight, height, and the cognitive, language, motor, social-emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Student's t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance. At 2 months of age, the mean composite scores of cognitive, motor, social-emotional, and adaptive behavior of BSID-III were significantly lower in atypical antipsychotic-exposed infants than the controls. More atypical antipsychotic-exposed infants had delayed development in cognitive, motor, social-emotional, and adaptive behavior domains as defined by the composite score of development in cognitive, motor, social-emotional, and adaptive behavior, but not in language, body weight, or height.

  19. THE ROLE OF ATYPICAL ANTIPSYCHOTIC DECREASING AGGRESIVENESS IN SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    Juvita Novia Anggraini Maria

    2013-03-01

    Full Text Available Schizophrenia is a psychiatry disorder accompanying by alteration of mind-set, perception,  thought, and behavior. Symptom of schizophrenia can be positive symptom and negative symptom. The positive symptom often became a fear for the others, that is aggresiveness as violance, suicide, ang homicide. Aggresiveness divided in five category, that is impulsivity, affective instability, anxiety/hyperarousal, cognitive disorganization, predatory/planned aggression. Pharmacology theraphy is a choice in decreasing aggresiveness in schizophrenia. Atypical antipsychotic theraphy indicate higher effectivity and fewer side effect than conventional antipsychotic.

  20. Atypical antipsychotic medications to control symptoms of delirium in children and adolescents.

    Science.gov (United States)

    Turkel, Susan Beckwitt; Jacobson, Julienne; Munzig, Elizabeth; Tavaré, C Jane

    2012-04-01

    Atypical antipsychotics have been documented to be effective in the management of delirium in adults, but despite considerable need, their use has been less studied in pediatric patients. A retrospective chart review was done to describe the use of atypical antipsychotics in controlling symptoms of delirium in children and adolescents. Pharmacy records at Children's Hospital Los Angeles were reviewed to identify patients to whom antipsychotic agents were dispensed over a 24-month period. Psychiatric inpatient consultations during the same 24-month period were reviewed. Patients 1-18 years old diagnosed with delirium given antipsychotics constituted the study population. Delirium Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when possible, at time antipsychotic was started to confirm the initial diagnosis of delirium and evaluate symptom severity, and again when antipsychotic was stopped, to assess symptom response. Olanzapine (n=78), risperidone (n=13), and quetiapine (n=19) were used during the 2 years of the study. Mean patient age, length of treatment, and response were comparable for the three medications. For patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores decreased significantly (pdelirium symptoms in pediatric patients while underlying etiology was addressed.

  1. Testing of bioactive-nanovesicles on hepatotoxicity of atypical antipsychotics via digital holography.

    Science.gov (United States)

    Ozturk Kirbay, Fatma; Geyik, Caner; Guler, Emine; Yesiltepe, Ozan; Gumus, Zinar Pinar; Odaci Demirkol, Dilek; Coskunol, Hakan; Timur, Suna

    2017-04-01

    Atypical antipsychotic drugs induce hepatic toxicity. Thus, it is of importance to eliminate the side effects of these drugs. Herein we describe the preparation of nanoemulsions with a dietary supplement; wheat germ oil (WGO), to ameliorate the liver damage induced by clozapine and olanzapine. THLE-2 cell line was used as a model to investigate the effects of these nanoemulsions on cell viability as well as antioxidative efficiency after antipsychotic insult. In this context, a conventional cell culture method; MTT was used along with a novel cellular imaging technique called digital holography (DH) to evaluate cell viability. Obtained data confirmed that both clozapine and olanzapine induced the liver damage in in vitro model and WGO nanoemulsions were found to be effective on cells and eliminate the cytotoxic effects of these drugs. Briefly, this study has some outputs as follows; it showed that different dietary supplements can be used in such formulations instead of their pristine forms to increase bioavailability. Also, DH was successfully applied for the monitoring of cell viability and it could be a promising approach as the reactive-free cytotoxicity test. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study.

    Science.gov (United States)

    Park, Yoonyoung; Bateman, Brian T; Kim, Dae Hyun; Hernandez-Diaz, Sonia; Patorno, Elisabetta; Glynn, Robert J; Mogun, Helen; Huybrechts, Krista F

    2018-03-28

    To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction. Cohort study using a healthcare database. Nationwide sample of patient data from more than 700 hospitals across the United States. 6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014. In-hospital mortality during seven days of follow-up from treatment initiation. Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were 1.90 (1.43 to 2.53) and 1.93 (1.34 to 2

  3. The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: a longitudinal MRI study.

    Science.gov (United States)

    Nicolo, John-Paul; Berger, Gregor E; Garner, Belinda A; Velakoulis, Dennis; Markulev, Connie; Kerr, Melissa; McGorry, Patrick D; Proffitt, Tina-Marie; McConchie, Mirabel; Pantelis, Christos; Wood, Stephen J

    2010-01-01

    Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r=-0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

  4. The effect of atypical antipsychotics on brain N-acetylaspartate levels in antipsychotic-naïve first-episode patients with schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Grošić V

    2014-07-01

    Full Text Available Vladimir Grošić,1 Petra Folnegovic Grošić,2 Petra Kalember,3,4 Maja Bajs Janović,2 Marko Radoš,3,4 Mate Mihanović,1 Neven Henigsberg3,51Psychiatric Hospital Sveti Ivan, Zagreb, 2University Hospital Center Zagreb, University of Zagreb, Zagreb, 3Polyclinic Neuron, Croatian Institute for Brain Research, Zagreb, 4Department of Neuropharmacology and Behavioral Pharmacology, Croatian Institute for Brain Research, University of Zagreb, Zagreb, 5Vrapče University Hospital, University of Zagreb, Zagreb, CroatiaPurpose: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics.Patients and methods: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using 1H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London – Drexel University, Letter–Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced.Results: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008 and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005. On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months.Conclusion: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn’t result

  5. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  6. Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost.

    Science.gov (United States)

    Mortimer, A; Williams, P; Meddis, D

    2003-01-01

    Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.

  7. Modifying the risk of atypical antipsychotics in the treatment of juvenile-onset schizophrenia.

    Science.gov (United States)

    Townsend, Lisa; Findling, Robert L

    2010-02-01

    This review summarizes the evidence for use of typical and atypical antipsychotic medications for the treatment of juvenile-onset schizophrenia. We highlight the risks and benefits of antipsychotic agents for youth with this disorder, paying special attention to weight gain and metabolic effects, an area of specific concern within child and adolescent psychiatry. We describe the seriousness of juvenile-onset schizophrenia and its impact on long-term functioning, noting that pharmacological treatment remains the standard of care for this disorder. We focus on weight gain and metabolic effects associated with atypical agents and review strategies to modify risks associated with these agents. We summarize strategies for attenuating the risk of weight gain for youth on atypical antipsychotics, including what is known about nutritional counseling and exercise programs as well as pharmacotherapy with adjunctive weight loss agents. Given the negative consequences associated with untreated schizophrenia, it appears that the most effective way to improve the risk:benefit ratio in the treatment of adolescents with schizophrenia is to reduce the risks associated with pharmacological treatment.

  8. Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

    Directory of Open Access Journals (Sweden)

    Pinaki Chakravarty

    2016-01-01

    Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

  9. Brain Volume Changes After Withdrawal of Atypical Antipsychotics in Patients With First-Episode Schizophrenia

    NARCIS (Netherlands)

    Boonstra, Geartsje; van Haren, Neeltje E. M.; Schnack, Hugo G.; Cahn, Wiepke; Burger, Huibert; Boersma, Maria; de Kroon, Bart; Grobbee, Diederick E.; Pol, Hilleke E. Hulshoff; Kahn, Rene S.

    The influence of antipsychotic medication on brain morphology in schizophrenia may confound interpretation of brain changes over time. We aimed to assess the effect of discontinuation of atypical antipsychotic medication on change in brain volume in patients. Sixteen remitted, stable patients with

  10. Antipsychotic prescribing in older people.

    Science.gov (United States)

    Neil, Wendy; Curran, Stephen; Wattis, John

    2003-09-01

    Antipsychotic medications have made a significant contribution to the care of the mentally ill people over the past 50 years, with good evidence that both typical and atypical agents are effective in the treatment of schizophrenia and related conditions. In addition they are widely used to good effect in other disorders including psychotic depression, dementia and delirium. Both typical and atypical agents may cause severe side-effects and, in the elderly in particular, there is an increased propensity for drug interactions. If used with care, antipsychotics are usually well tolerated, especially the atypical drugs. Although antipsychotics are effective at reducing psychotic symptoms their limitations should be recognised. They do not 'cure' the underlying illness, and the management of psychotic and behavioural symptoms must take into consideration treatment of physical illness as well as psychosocial interventions. In addition, the antipsychotic effect may take one to two weeks to be evident so doses should not be increased too rapidly. Often small doses are effective in the elderly if they are given sufficient time to work. As our understanding of the mechanisms of psychosis improves it is hoped that new drugs will be developed with novel mechanisms of action with improved efficacy and reduced side-effects. There are several drugs in development, some sharing similarities to currently available agents whilst others have novel mechanisms of actions involving glutamate and nicotinic receptors. Pharmacogenetics is also likely to be increasingly important over the next few years. As the genetic basis of many psychiatric disorders becomes more clearly established it is likely that drugs specifically designed for particular sub-groups of receptors will be developed. Finally, although the pharmacological treatment of psychotic disorders in younger people has been given considerable attention, there is a paucity of good quality research on antipsychotic drug use in

  11. Antipsychotics and Associated Risk of Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Weeke, Peter; Jensen, Aksel; Folke, Fredrik

    2014-01-01

    % confidence interval [CI]:1.23-1.89) as was use with typical antipsychotics (OR= 1.66, CI: 1.27-2.17). By contrast, overall atypical antipsychotics drug use was not (OR= 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs were associated with OHCA, haloperidol (OR= 2.43, CI: 1...

  12. Use of antipsychotics in the treatment of depressive disorders

    Institute of Scientific and Technical Information of China (English)

    Ping WANG; Tianmei SI

    2013-01-01

    There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.

  13. Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

    Science.gov (United States)

    Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

    2010-04-01

    After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was

  14. Sertindole versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; Schmid, Franziska; Lewis, Ruth; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether and, if so, how much the effects of the various second generation antipsychotics differ is a matter of debate. Objectives To evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) and ClinicalTrials.gov (February 2009). Selection criteria We included all randomised trials comparing oral sertindole with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI −8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33

  15. Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

    Science.gov (United States)

    Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

    2013-08-01

    Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    Science.gov (United States)

    Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

    2016-01-01

    Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180

  17. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    Directory of Open Access Journals (Sweden)

    Maurizio Pompili

    2016-10-01

    Full Text Available Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia. We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior.

  18. [Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].

    Science.gov (United States)

    Haefliger, T; Bonsack, C

    2006-01-01

    Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case

  19. Atypical antipsychotics for disruptive behaviour disorders in children and youths.

    Science.gov (United States)

    Loy, Jik H; Merry, Sally N; Hetrick, Sarah E; Stasiak, Karolina

    2017-08-09

    This is an update of the original Cochrane Review, last published in 2012 (Loy 2012). Children and youths with disruptive behaviour disorders may present to health services, where they may be treated with atypical antipsychotics. There is increasing usage of atypical antipsychotics in the treatment of disruptive behaviour disorders. To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. The aim was to evaluate each drug separately rather than the class effect, on the grounds that each atypical antipsychotic has different pharmacologic binding profile (Stahl 2013) and that this is clinically more useful. In January 2017, we searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers. Randomised controlled trials of atypical antipsychotics versus placebo in children and youths aged up to and including 18 years, with a diagnosis of disruptive behaviour disorders, including comorbid ADHD. The primary outcomes were aggression, conduct problems and adverse events (i.e. weight gain/changes and metabolic parameters). The secondary outcomes were general functioning, noncompliance, other adverse events, social functioning, family functioning, parent satisfaction and school functioning. We used standard methodological procedures expected by Cochrane. Two review authors (JL and KS) independently collected, evaluated and extracted data. We used the GRADE approach to assess the quality of the evidence. We performed meta-analyses for each of our primary outcomes, except for metabolic parameters, due to inadequate outcome data. We included 10 trials (spanning 2000 to 2014), involving a total of 896 children and youths aged five to 18 years. Bar two trials, all came from an outpatient setting. Eight trials assessed risperidone, one assessed quetiapine and one assessed ziprasidone. Nine trials assessed acute efficacy (over four to 10 weeks); one of which combined

  20. Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

    Science.gov (United States)

    Beninger, Richard J

    2006-12-01

    Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

  1. Study on effects of an atypical antipsychotic agent, quetiapine, on regional cerebral blood flow with 99mTc-ECD SPECT in drug-naive or unmedicated schizophrenic patients

    International Nuclear Information System (INIS)

    Monkawa, Akikazu

    2007-01-01

    The objective of this study was to investigate the underlying mechanisms of intracerebral actions or clinical efficacies of quetiapine, an atypical antipsychotic agent and a multi-action receptor targeting agent (MARTA), and the influences of quetiapine on absolute regional cerebral blood flows (rCBFs) of schizophrenic patients. Correlations between rCBFs and psychotic symptoms were also examined. Subjects comprised 12 patients who met the ICD-10 criteria for schizophrenia. All patients were drug-naive or unmedicated. Using single photon emission computed tomography (SPECT) with 99m Tc-ethyl cysteinate dimer (ECD), rCBFs were measured. Psychotic symptoms were evaluated with positive and negative syndrome scale (PANSS). The evaluations of SPECT and PANSS were repeated before and after oral 2-week administration of quetiapine 300 mg/day in all patients and after subsequent 2-week administration of quetiapine 600 mg/day in 6 patients. Administration of quetiapine yielded no significant changes in rCBFs at any dose. And there were no significant correlations between the scores of PANSS and the values of rCBFs in any region, though the scores of PANSS decreased after qutiapine administration. It has been reported that, a typical antipsychotic agent, haloperidol, and an atypical antipsychotic agent, risperidone, decrease rCBFs in the cerebral cortex in dose-dependently in drug-naive or unmedicated schizophrenic patients. This phenomenon is considered to be attributable to a secondary inactivation of the cerebral cortex due to D2 receptor blockade of haloperidol or risperidone in the striatum through the cortico-striatal-thalamic pathway. In the frame of this hypothesis, results of this study may relate to the lower degree of D2 blockade induced by quetiapine than that produced by haloperidol and risperidone. (author)

  2. Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5-HT2A Antagonist

    Directory of Open Access Journals (Sweden)

    Mahantesh Namdev Jadhav

    2013-01-01

    Full Text Available Schizophrenia is a mental disorder manifested largely by disintegration of thought processes and emotional responsiveness. Given the therapeutic and toxic limitations of clinically available drugs, it is clear that there is still a need for the development of new generation antipsychotic agents with an improved clinical profile. Development of novel hybrid atypical tricyclic antipsychotic pharmacophore was achieved using direct (by measuring docking score of designed molecules on modelled 5- receptor and indirect (current, clinically available therapeutic agents’ data drug design approaches.

  3. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

    International Nuclear Information System (INIS)

    Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

    1988-01-01

    Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline

  4. Association between Ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients

    OpenAIRE

    Yang Yongfeng; Li Wenqiang; Zhao Jingyuan; Zhang Hongxing; Song Xueqin; Xiao Bo; Yang Ge; Jiang Chengdi; Zhang Dai; Yue Weihua; Lv Luxian

    2012-01-01

    Abstract Background Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no...

  5. First Episode Schizophrenia Regional Cerebral Blood Flow Assessment after Atypical Antipsychotics

    International Nuclear Information System (INIS)

    Rimbu, A.; Mititelu, R.; Marinescu, G.; Ghita, S.; Mazilu, C.; Codorean, I.; Gheorghe, M.

    2006-01-01

    Full text: Aim: Since regional cerebral blood flow (rCBF) findings in schizophrenic patients are inconsistent, the aim of our study was to evaluate and compare rCBF in the first episode of schizophrenia, before and after atypical antipsychotic treatment. Method: 21 patients who met criteria for schizophrenia were assessed PANSS score and tomographic brain perfusion (SPECT). The treatment was administered for 10-12 weeks and the dose was 4.8mg/day Risperidone, 11.6mg/day Olanzepine, 440mg/day Quetiapine. After finishing treatment all patients underwent a control SPECT study. Results: PANSS scores revealed two groups: group A-14 patients with predominant positive symptoms; 9 received Olanzapine and 5 Quetiapine. In group B -7 patients with predominant negative symptoms received Risperidone. Positive symptoms were associated with hypoperfusion in posterior parietal regions and superior temporal gyrus, bilaterally; for negative symptoms we found hypoperfusion in prefrontal cortex, predominantly in left side and a hyper perfusion in left basal ganglia. All patients that received atypical antipsychotic drugs had clinical improvement and decreases in PANSS scores; the control SPECT analysis revealed the same cortical changes as first studies in 15 patients and an increase of the rCBF in frontal lobes for 4 patients. 14 patients we noticed an increased rCBF at subcortical level, especially in left caudate nuclei. Conclusions: We found nonspecific features of rCBF in patients with first episode of schizophrenia, suggesting a perfusion dynamic balance rather than a fixed model. Those aspects are much more related to clinical symptoms, than to the therapeutical response. The rCBF changes in subcortical level after treatment (64.4% increase of rCBF; 35.6% not modified), can have a good prognostic value for therapeutic response. (author)

  6. Dislipidemias e antipsicóticos atípicos Dyslipidemias and atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Edilberto Amorim de Cerqueira Filho

    2006-01-01

    Full Text Available OBJETIVO: Um progressivo número de evidências surge associando o uso de antipsicóticos atípicos a dislipidemias, situação pouco atentada por considerável número de psiquiatras e preditora importante de doenças cardiovasculares (DCVs e de morbimortalidade. O propósito deste estudo é revisar a associação entre o uso de antipsicóticos atípicos e o desenvolvimento de dislipidemias em pacientes com esquizofrenia. MÉTODOS: A pesquisa bibliográfica utilizou os bancos de dados MEDLINE e Scientific Electronic Library Online (SciELO, com os descritores: schizophrenia, dyslipidemia, hyperlipidemia e lipids, para identificar artigos originais publicados no período de 1997 a setembro de 2006. RESULTADOS: Os artigos foram agrupados segundo cada agente terapêutico, de acordo com o seu impacto sobre o perfil lipídico. CONCLUSÃO: Observa-se maior risco de desenvolvimento de dislipidemias em pacientes com esquizofrenia em uso de alguns antipsicóticos atípicos. Intervenções comportamentais e farmacológicas devem ser associadas nos indivíduos com esquizofrenia em tratamento antipsicótico e que desenvolvem dislipidemias.OBJECTIVE: Pieces of evidence appear associating the use of atypical antipsychotics to dyslipidemias, situation that is of little attention by considerable number of psychiatrists and important predictor of cardiovascular illnesses and morbi-mortality. The intention of this study is to review the association between the atypical antipsychotic use and the development of dyslipidemias in patients with schizophrenia. METHODS: The bibliographical research used databases MEDLINE and SciELO, for the key words: schizophrenia, dyslipidemia, hyperlipidemia and lipids, with the objective to identify original articles published in the period of 1997 to September 2006. RESULTS: The articles were distributed according to each therapeutic agent and their impact on lipidic profile. CONCLUSION: Higher risk of development of dyslipidemias

  7. Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics

    DEFF Research Database (Denmark)

    Jørgensen, Anders; Knorr, Ulla Benedichte Søsted; Soendergaard, Mia Greisen

    2015-01-01

    ratio are positively correlated to measures of oxidative stress. METHODS: We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography...... in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA....... Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology. RESULTS: Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA...

  8. Cost-effectiveness of an atypical conventional antipsychotic in South Africa: An economic evaluation of quetiapine versus haloperidol in the treatment of patients partially responsive to previous antipsychotics

    Directory of Open Access Journals (Sweden)

    Robin Emsley

    2004-10-01

    Full Text Available Background. The introduction of a new generation of atypical antipsychotic agents has raised difficult economic and ethical questions, particularly in lower-income countries. The reported tolerability and efficacy advantages of the atypical antipsy- chotics over their conventional predecessors have to be weighed against their higher acquisition costs. Pharmaco-eco- nomic studies conducted in Western countries consistently report cost advantages or cost neutrality for these new agents. However, considerable differences in health care service pro- vision make it difficult to generalise these findings to South Africa. Method. We compared the direct costs (private and public sector of treating schizophrenia with an atypical antipsychotic quetiapine, and with a conventional antipsychotic haloperidol, by adapting a decision-analytic pharmaco-economic model for South African circumstances. The sample comprised patients partially responsive to antipsychotics, who had partic- ipated in a multinational randomised controlled trial compar- ing the efficacy and safety of quetiapine versus haloperidol. Results. The estimated total direct cost for the treatment with quetiapine in South Africa was slightly less than for haloperidol for various models in both the private and the public sectors. Conclusions. Significant differences in health care provision make pharmaco-economic studies conducted in other coun- tries invalid for South African circumstances. Previously queti- apine treatment did not result in direct cost savings in South Africa. However, the recently introduced legislation to estab- lish single exit prices for medications has resulted in the cost of quetiapine treatment declining by 36.7% and that of haloperi- dol by 13%. This has translated into an overall direct cost sav- ing for quetiapine in both the private and public sector models. This, together with additional indirect advantages of the atypi- cal antipsychotics such as improved quality of

  9. Comparison between risperidone, an atypical antipsychotic agent and haloperidol, a conventional agent used to treat schizophrenia

    International Nuclear Information System (INIS)

    Rehman, A.; Jawed, M.; Maheshwari, M.P.

    2012-01-01

    An observational and comparative study was conducted to compare the functional outcome between the patients treated with conventional antipsychotic agent haloperidol and typical antipsychotic agent, Risperidone (Risperidal). A total of 32 patients were included in the study with established schizophrenia according to (DSM iv). The data was processed on SSPE 10th version. The primary outcome measure was the improvement of negative symptoms of schizophrenia and secondary outcome measure was to observe the superiority of the atypical drug Risperid one over conventional agent haloperidol regarding side effects. Patients were assessed at baseline, 2nd and 8th week, using four tools of assessment. For treatment group receiving haloperidol mean was 47.2+-11.50 at 8th week and for Risperidone treatment group mean was 43+-14.68. The P values for all the parameters in the Clozapine group were significant as compared to haloperidol. (author)

  10. Antipsychotic-induced Hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    Suheyla Dogan Bulut

    2015-06-01

    Full Text Available Prolactin provides the growth of the mammary gland during pregnancy and synthesis and preparation of breast milk for lactation. Antipsychotics and antidepressants that are frequently used in psychiatry, cause hyperprolactinemia. The prevalent opinion is that especially typical antipsychotics increase prolactin levels primarily by blocking D2 receptors in the anterior pituitary. The effects of atypical antipsychotics on hyperprolactinemia vary. Hyperprolactinemia causes galactorrhea, gynecomastia, sexual dysfunction, infertility, acne, hirsutism in women, weight gain, obesity and mood changes in addition to menstrual irregularities such as oligomenorrhea, polymenorrhea and amenorrhea. In the long term, hyperprolactinemia may cause reduction in bone density and osteoporosis. Hyperprolactinemia as a side effect of antipsychotics drugs and its treatment will be reviewed in this article. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 109-124

  11. Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

    Science.gov (United States)

    Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

    Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats

    DEFF Research Database (Denmark)

    Oliveras, Ignasi; Sánchez-González, Ana; Sampedro-Viana, Daniel

    2017-01-01

    acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). RESULTS: RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical...... antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70 dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI...

  13. Zotepine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Subramanian, Selvizhi; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Kissling, Werner; Leucht, Stefan; Komossa, Katja

    2014-01-01

    Background In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. Objectives To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteria We included only randomised clinical controlled trials that compared zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses. Data collection and analysis SS and KK extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results We included three studies (total n=289; 2 RCTs zotepine vs clozapine; 1 RCT zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the

  14. [Therapeutic options for weight management in schizophrenic patients treated with atypical antipsychotics].

    Science.gov (United States)

    Cordes, J; Sinha-Röder, A; Kahl, K G; Malevani, J; Thuenker, J; Lange-Asschenfeldt, C; Hauner, H; Agelink, M W; Klimke, A

    2008-12-01

    Extensive, selective literature review of 2500 articles from the last years (up to December 2007) predominantly from Medline and Cochrane, using as search terms "antipsychotic or schizophrenia or individual drug names (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone)" and the terms "BMI, weight gain, metabolic syndrome, diabetes, lipid(s), cholesterol, triglycerides" was conducted. Regardless of the advantages ascribed to atypical antipsychotics and the special effectiveness of clozapine in patients resistant to therapy and at risk for suicide, the probability of weight gain is considerably increased for some of these substances. Patients with schizophrenia have a considerably reduced life expectancy associated with an increased prevalence of cardiovascular risk factors. There is a lack of practical guidelines integrated into clinical psychiatric care for the management of cardiovascular risk factors. The monitoring of patients treated with atypics, which has been recommended in the APA/ADA Consensus Paper in light of these facts, is insufficiently established in clinical practice. A regular monitoring can convey self control and motivation to the patient. In the case of corresponding risk constellations further decisions regarding indication and therapy have to be considered. Especially patients with a high cardiovascular risk profile are highly recommended to participate in a weight-management program for prevention purposes. Such a special program should include elements of dietetic treatment and behaviour and exercise therapy. First controlled studies suggest an effective prevention of weight gain and metabolic changes when applying such a structured program. The practice oriented step by step concept presented here is meant to provide points of reference for the implementation of required medical and psychoeducative measures facilitating the management of weight and further cardiovascular risk factors in the context of

  15. Antipsychotic prescription patterns and treatment costs of ...

    African Journals Online (AJOL)

    Peshawar, Pakistan and to analyze the treatment costs associated with these drugs. Methods: One hundred ..... Kendall T. The rise and fall of the atypical antipsychotics. ... size determination in health studies: a practical manual. 1991. 18.

  16. Atypical antipsychotics as a possible treatment option for irritable bowel syndrome.

    Science.gov (United States)

    Pae, Chi-Un; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S

    2013-05-01

    Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder (FGID) that is characterised by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits. Although the pathophysiology of IBS is not fully understood, it is believed that psychiatric comorbidities are highly common in such patients. A variety of psychotropic medications are widely used in the treatment of IBS, particularly older antidepressants such as tricyclic antidepressants (TCAs). With the advent of newer antidepressant classes with better safety and tolerability compared with TCAs, such as serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), clinicians now have more advanced treatment options for treating IBS. Additionally, some atypical antipsychotics (AAs) have recently received approval for treatment of major depressive disorder (MDD). Some AAs may have potentials based on their pharmacodynamic profile and proven benefit for mood symptoms, pain, anxiety and sleep disturbances. This article describes the potential rationale, clinical data and practical aspects involved in the use of AAs for patients with IBS. Atypical antipsychotics (AAs) may have a role in the treatment of irritable bowel syndrome (IBS) based on the currently available findings, although there is no clear evidence, and a number of clinical issues to be addressed in the use of AAs for the treatment of IBS.

  17. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

    International Nuclear Information System (INIS)

    Creese, I.; Florijn, W.J.; Tarazi, F.I.

    1997-01-01

    Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [ 3 H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D 3 receptors was not changed in any brain region by any of the drug treatments. [ 3 H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [ 3 H]nemonapride and [ 3 H]spiperone binding to dopamine D 2 -like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [ 3 H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [ 3 H]nemonapride and [ 3 H]spiperone binding in caudate-putamen, whereas it did not affect [ 3 H]raclopride binding. Clozapine did not significantly change D 2 -like striatal binding of [ 3 H]nemonapride, [ 3 H]spiperone or [ 3 H]raclopride. The differences in radioligand binding suggest that [ 3 H]nemonapride and [ 3 H]spiperone may be binding to additional subsets of dopamine D 2 -like receptors (including D 4 -like receptors) that are not recognized by [ 3 H]raclopride, which has high affinity for D 2 and D 3 receptors only.Quantification of [ 3 H]nemonapride or [ 3 H]spiperone binding in the presence of 300 nM raclopride (to block D 2 and D 3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D 4 -like receptors in the caudate-putamen using either radioligand. These results suggest that D 4 -like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium.

    Science.gov (United States)

    Comai, Stefano; Tau, Michael; Pavlovic, Zoran; Gobbi, Gabriella

    2012-04-01

    Patients experiencing mental disorders are at an elevated risk for developing aggressive behavior. In the past 10 years, the psychopharmacological treatment of aggression has changed dramatically owing to the introduction of atypical antipsychotics on the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.This review (second of 2 parts) uses a translational medicine approach to examine the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis (serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid) and the neuropharmacological rationale for using atypical antipsychotics, anticonvulsants, and lithium in the therapeutics of aggressive behavior. A critical review of all clinical trials using atypical antipsychotics (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone, ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate, lamotrigine, and gabapentin), and lithium are presented. Given the complex, multifaceted nature of aggression, a multifunctional combined therapy, targeting different receptors, seems to be the best strategy for treating aggressive behavior. This therapeutic strategy is supported by translational studies and a few human studies, even if additional randomized, double-blind, clinical trials are needed to confirm the clinical efficacy of this framework.

  19. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Arlan L. Rosenbloom

    2010-01-01

    Full Text Available There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  20. Exposure-response relationship of typical and atypical antipsychotics assessed by the positive and negative syndrome scale (PANSS) and its subscales

    NARCIS (Netherlands)

    Pilla Reddy, Venkatesh; Suleiman, Ahmed; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2011-01-01

    Objectives: It has been suggested that atypical antipsychotics (ATAPs), are more effective towards negative symptoms than typical antipsychotics (TAPs) in schizophrenic patients.[1,2] To quantify the above statement, we aimed i) to develop a PK-PD model that characterizes the time course of PANSS

  1. A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics.

    Science.gov (United States)

    Weber, Mary; Wyne, Kathleen

    2006-03-01

    Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.

  2. Cost-Utility Analysis of Depot Atypical Antipsychotics for Chronic Schizophrenia in Croatia.

    Science.gov (United States)

    Jukic, Vlado; Jakovljevic, Miro; Filipcic, Igor; Herceg, Miroslav; Silic, Ante; Tomljanovic, Tatjana; Zilbershtein, Roman; Jensen, Rasmus C D; Hemels, Michiel E H; Einarson, Thomas R

    As a nation with a developing economy, Croatia is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. We conducted a pharmacoeconomic analysis to determine the cost-effectiveness of atypical depots in Croatia. A 1-year decision-analytic framework modeled drug use. We determined the average direct cost to the Croatian Institute for Health Insurance of using depot formulations of paliperidone palmitate long-acting injectable (PP-LAI), risperidone LAI (RIS-LAI), or olanzapine LAI (OLZ-LAI). An expert panel plus literature-derived clinical rates populated the core model, along with costs adjusted to 2012 by using the Croatian consumer price index. Clinical outcomes included quality-adjusted life-years, hospitalization rates, emergency room treatment rates, and relapse days. Robustness of results was examined with one-way sensitivity analyses on important inputs; overall, all inputs were varied over 10,000 simulations in a Monte Carlo analysis. Costs (quality-adjusted life-years) per patient were €5061 (0.817) for PP-LAI, €5168 (0.807) for RIS-LAI, and €6410 (0.812) for OLZ-LAI. PP-LAI had the fewest relapse days, emergency room visits, and hospitalizations. Results were sensitive against RIS-LAI with respect to drug costs and adherence rates, but were generally robust overall, dominating OLZ-LAI in 77.3% and RIS-LAI in 56.8% of the simulations. PP-LAI dominated the other drugs because it had the lowest cost and best clinical outcomes. Compared with depots of olanzapine and risperidone and oral olanzapine, PP-LAI was the cost-effective atypical LAI for treating chronic schizophrenia in Croatia. Using depot paliperidone in place of either olanzapine or risperidone would reduce the overall costs of caring for these patients. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

  3. Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

    Directory of Open Access Journals (Sweden)

    Reis Helton J

    2010-06-01

    Full Text Available Abstract Background Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D2. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC: Neuronal Calcium Sensor-1 (NCS-1 and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D2 internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT and PC12 cells stably overexpressing NCS-1 (PC12 Clone with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment. Results We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol or atypical (Clozapine and Risperidone antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments. Conclusions Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.

  4. Using Functional Analysis Methodology to Evaluate Effects of an Atypical Antipsychotic on Severe Problem Behavior

    Science.gov (United States)

    Danov, Stacy E.; Tervo, Raymond; Meyers, Stephanie; Symons, Frank J.

    2012-01-01

    The atypical antipsychotic medication aripiprazole was evaluated using a randomized AB multiple baseline, double-blind, placebo-controlled design for the treatment of severe problem behavior with 4 children with intellectual and developmental disabilities. Functional analysis (FA) was conducted concurrent with the medication evaluation to…

  5. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Ashwin Kamath

    2018-01-01

    Full Text Available The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = −4.44 [95% CI, −7.00 to −1.88]; p=0.0007; I2 = 13%, but not the systolic blood pressure (mean difference = −4.23 [95% CI, −8.11 to −0.36]; p=0.03; I2 = 0%. Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

  6. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Kamath, Ashwin; Rather, Zahoor Ahmad

    2018-01-01

    The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = -4.44 [95% CI, -7.00 to -1.88]; p = 0.0007; I 2 = 13%), but not the systolic blood pressure (mean difference = -4.23 [95% CI, -8.11 to -0.36]; p = 0.03; I 2 = 0%). Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

  7. Pharmacokinetic-pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia : Part II: The use of subscales of the PANSS score

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    Background and objectives: The superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was

  8. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

    Energy Technology Data Exchange (ETDEWEB)

    Creese, I; Florijn, W J; Tarazi, F I [Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ (United States)

    1997-04-14

    Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [{sup 3}H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D{sub 3} receptors was not changed in any brain region by any of the drug treatments. [{sup 3}H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding to dopamine D{sub 2}-like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [{sup 3}H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding in caudate-putamen, whereas it did not affect [{sup 3}H]raclopride binding. Clozapine did not significantly change D{sub 2}-like striatal binding of [{sup 3}H]nemonapride, [{sup 3}H]spiperone or [{sup 3}H]raclopride. The differences in radioligand binding suggest that [{sup 3}H]nemonapride and [{sup 3}H]spiperone may be binding to additional subsets of dopamine D{sub 2}-like receptors (including D{sub 4}-like receptors) that are not recognized by [{sup 3}H]raclopride, which has high affinity for D{sub 2} and D{sub 3} receptors only.Quantification of [{sup 3}H]nemonapride or [{sup 3}H]spiperone binding in the presence of 300 nM raclopride (to block D{sub 2} and D{sub 3} receptors) revealed that haloperidol, raclopride and clozapine up-regulated D{sub 4}-like receptors in the caudate-putamen using either radioligand. These results suggest that D{sub 4}-like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    Marum, R.J. van; Wegewijs, M.A.; Loonen, A.J.M.; Beers, E.

    2007-01-01

    Objective: Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method: Case reports of hypothermia in APD-users found

  10. A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

    Science.gov (United States)

    Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

    2017-10-01

    Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A Survey of the Tardive Dyskinesia Induced by Antipsychotic Drugs in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Naser tabibi

    2010-11-01

    Full Text Available "nObjective: Tardive Dyskinesia (TD, is one of the important problems of the patients with schizophrenia. The emergence of these side effects depends on so many factors such as the patients' age and the duration of antipsychotic treatment. By discovering new drugs (Atypical, there has been an outstanding decrease in the emergence of these side effects. The present study investigates the symptoms of TD in the Patients with schizophrenia who were under  treatments for more than 6 months. "nMethod: The sample of this study was 200 Patients with schizophrenia of four wards in Razi hospital (two acute and two chronic wards who were hospitalized in the winter of 2006 and were qualified for this study. The subjects were 101 males and 99 females who were younger than 60 and had received antipsychotic drugs for at least 6 months. After psychiatric interview and filling the demographic questionnaire by the patients, the required information about the drugs and the intensity of the symptoms was acquired. Then clinical and physical examinations of tardive dyskinesia were done. Next, the tardive dyskinesia disorders' check list (AIMS was used. Findings of this cross-sectional, descriptive study were analyzed by SPSS. "nResults: There was a high ratio of 95% between TD and the age factor (P=0.05. There was no relationship between symptoms frequency and duration of treatment (P=0.68. Facial muscles and oral zones were mostly involved in T.D disorder (72%. "nConclusion: No significant difference was observed between nine fold symptoms of T.D in patients who were using traditional drugs and those who were using the new ones (typical and atypical. Findings showed that in the intensity of the symptoms, gender does not play a major role.

  12. Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: A network meta-analysis.

    Science.gov (United States)

    Bai, Zhihua; Wang, Guoqiang; Cai, Shangli; Ding, Xindi; Liu, Weiwei; Huang, Depei; Shen, Weidi; Zhang, Juncheng; Chen, Kui; Yang, Yuqing; Zhang, Lili; Zhao, Xiaochen; Ouyang, Qiong; Zhao, Jingping; Lu, Huafei; Hao, Wei

    2017-07-01

    We aimed to create hierarchies of the efficacy, acceptability and tolerability of eight atypical antipsychotics in the treatment of Chinese patients with acute schizophrenia. We systematically searched for RCT articles published between January 1st 2005 and December 31st 2014 in electronic databases (Medline, Pubmed, Embase, the Cochrane Library and ClinicalTrial.gov for studies in English and the China National Knowledge Infrastructure, Wan Fang, and VIP Information/Chinese Scientific Journals Database for studies in Chinese). The primary outcome was efficacy, as measured by the change of PANSS total score. Pairwise comparisons were performed using random-effects model by the Dersimonian-Laird method and network meta-analyses were performed in a Bayesian set. Sixty high-quality RCTs with 6418 participants were included. A pattern of superiority from olanzapine, paliperidone and amisulpride was seen in the primary outcome. Only paliperidone was found better than aripiprazole (odds ratio, 0.49 [95% credible intervals, 0.25 to 0.99]), ziprasidone (0.42 [0.21 to 0.85]) and quetiapine (0.36 [0.13 to 0.93]) in terms of all-cause discontinuation. The best and worst drugs in terms of weight gain, EPS and somnolence were aripiprazole and olanzapine, clozapine and amisulpride, aripiprazole and clozapine, respectively. The rank of efficacy did not change substantially in sensitivity analyses or in meta-regressions. Our findings provided the hierarchies of eight antipsychotics in efficacy, acceptability and tolerability. These findings are expected to help Chinese clinicians to select the appropriate antipsychotic drug for their patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Unresolved Issues for Utilization of Atypical Antipsychotics in Schizophrenia: Antipsychotic Polypharmacy and Metabolic Syndrome

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    Sang Won Jeon

    2017-10-01

    Full Text Available Atypical antipsychotics (AAP are the prevailing form of schizophrenia treatment today due to their low side effects and superior efficacy. Nevertheless, some issues still need to be addressed. First, there are still a large number of patients with treatment-resistant schizophrenia (TRS, which has led to a growing trend to resort to AAP polypharmacy with few side effects. Most clinical treatment guidelines recommend clozapine monotherapy in TRS, but around one third of schizophrenic patients fail to respond to clozapine. For these patients, with clozapine-resistant schizophrenia AAP polypharmacy is a common strategy with a continually growing evidence base. Second, AAP generally have great risks for developing metabolic syndrome, such as weight gain, abnormality in glucose, and lipid metabolism. These metabolic side effects have become huge stumbling blocks in today’s schizophrenia treatment that aims to improve patients’ quality of life as well as symptoms. The exact reasons why this particular syndrome occurs in patients treated with AAP is as yet unclear though factors such as interaction of AAP with neurotransmitter receptors, genetic pholymorphisms, type of AAPs, length of AAP use, and life style of schizophrenic patients that may contribute to its development. The present article aimed to review the evidence underlying these key issues and provide the most reasonable interpretations to expand the overall scope of antipsychotics usage.

  14. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    van Marum, Rob J.; Wegewijs, Michelle A.; Loonen, Anton J. M.; Beers, Erna

    Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Methods Case reports of hypothermia in APD-users found in PUBMED or

  15. Effects of Clozapine and other Atypical Antipsychotics on Infants Development Who Were Exposed to as Fetus: A Post-Hoc Analysis.

    Directory of Open Access Journals (Sweden)

    Ping Shao

    Full Text Available To investigate the developmental effects of clozapine and other atypical antipsychotics on infants who were exposed to as fetus.The developmental progress of 33 infants who were exposed to clozapine as fetus was compared to 30 infants who were exposed to risperidone, olanzapine or quetiapine as fetus by assessing Apgar scoring, birth weight at birth, body weight, height, and the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III at months 2, 6 and 12 of age. Five subscale scores of BSID-III including cognitive, language, motor, social-emotional, and adaptive behavior were also compared. Student's t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance.Of the 63 infants, 58 (92.1% completed a 12-month study period. At the age of 2 and 6 months, mean adaptive behavior scores of BSID-III were significantly lower in clozapine-exposed infants than infants who exposed to other atypical antipsychotic at 2 and 6 months of age. More clozapine-exposed infants had delayed development (defined as the subscale score of <85 for adaptive behavior at 2 and 6 months of age. There was no difference between the two groups for cognitive, language, motor, social and emotional at 2, 6 and 12 months of age. More infants who were exposed to clozapine as fetus (25 of 33, 75.8% had disturbed sleep and a labile state than those who were exposed to other atypical antipsychotics (8 of 30, 26.7% during 2 months of age (P<0.001.These results suggest that clozapine has more adaptive behavior effects on infants who were exposed to as a fetus than other atypical antipsychotics at 2 and 6 months of age.ClinicalTrials.gov NCT01479400.

  16. Novel versus conventional antipsychotic drugs.

    Science.gov (United States)

    Love, R C

    1996-01-01

    Novel antipsychotic agents differ from conventional ones in several key characteristics, including effectiveness, adverse reactions, and receptor-binding profile. Most of the newer agents have an affinity for the serotonin 5HT2 receptor that is at least 10 times greater than that for the dopamine D2 receptor. This increased affinity for the serotonin receptor may be responsible for another distinguishing characteristic of novel antipsychotic agents--decreased frequency of extrapyramidal side effects. These side effects, which include pseudoparkinsonism, acute dystonias, and akathisia, frequently are the reason for noncompliance with conventional drug therapy. The newer drugs are often effective in patients resistant to treatment with conventional agents. They also appear to reduce the negative symptoms of schizophrenia in many patients.

  17. The effect of verbalization strategy on wisconsin card sorting test performance in schizophrenic patients receiving classical or atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Cavallaro Roberto

    2006-01-01

    Full Text Available Abstract Background A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed. The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST remediation, in subjects on classical vs atypical antipsychotic (AP treatment. Methods Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable and AP treatment (i.e. atypical vs. classical. Results Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs. Conclusion Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs.

  18. Diabetic control and atypical antipsychotics: a case report

    Directory of Open Access Journals (Sweden)

    Gaston Romina

    2008-05-01

    Full Text Available Abstract Introduction People with schizophrenia are at increased risk of developing metabolic disturbances. This risk may be further exacerbated by the use of antipsychotic agents. Research is still ongoing to determine the metabolic impact of antipsychotics on glucose regulation. In this case report we review some of the possible mechanisms of action of antipsychotic medication on glucose regulation. Case presentation We present the case of a 50-year-old man diagnosed with paranoid schizophrenia who developed type 2 diabetes mellitus whilst on treatment with second generation antipsychotics (SGA. His diabetes was controlled by a combination of antidiabetic drugs that were associated with his psychotropic treatment. Due to deterioration in his mental state, the patient was admitted on two occasions to a psychiatric unit during which his prescribed medication (olanzapine and risperidone was discontinued and changed to aripiprazole. On both occasions, the patient suffered hypoglycaemic episodes and his antidiabetic treatment had to be adjusted accordingly. The patient did not require any antidiabetic treatment whilst on aripiprazole during the follow up period. Conclusion Clinicians face regular dilemmas in trying to find the right balance between achieving control over a patient's mental illness and reducing any adverse effects associated with the prescribed medication. In patients receiving concomitant antidiabetic therapy, caution should be exercised when changing from one SGA to another. Whilst more longitudinal data are required, a trial of alternative SGAs, including aripiprazole in those developing type 2 diabetes and impaired glucose tolerance may be a worthwhile therapeutic option.

  19. Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics Revisão da eficácia do placebo nos ensaios clínicos que comparam antipsicóticos típicos e atípicos

    Directory of Open Access Journals (Sweden)

    Irismar Reis de Oliveira

    2009-03-01

    Full Text Available OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.OBJETIVO: Revisar a eficácia do placebo em comparação com a dos antipsicóticos atípicos e típicos no tratamento da esquizofrenia e do transtorno

  20. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

    Science.gov (United States)

    Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

    2013-03-05

    Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. A critical assessment of antipsychotic drug monitoring.

    Science.gov (United States)

    Waraska, J; Nagle, J D

    1987-06-01

    Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

  2. Antipsychotic drug treatment for patients with schizophrenia: theoretical background, clinical considerations and patients preferences

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

      The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side......-effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

  3. Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Haiyun eXu

    2011-07-01

    Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

  4. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2014-08-08

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  5. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    International Nuclear Information System (INIS)

    Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

    2014-01-01

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  6. Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

    Science.gov (United States)

    Jensen, Ralph J

    2016-12-01

    In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

  7. Risperidone versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with

  8. Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

    Science.gov (United States)

    Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

    2016-09-01

    α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

  9. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro.

    Science.gov (United States)

    Sárvári, Anitta K; Veréb, Zoltán; Uray, Iván P; Fésüs, László; Balajthy, Zoltán

    2014-08-08

    Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Behavioral and metabolic effects of the atypical antipsychotic ziprasidone on the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Priscila Gubert

    Full Text Available Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans. Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide. Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone's effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively. These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction.

  11. Patterns of Adherence to Oral Atypical Antipsychotics Among Patients Diagnosed with Schizophrenia.

    Science.gov (United States)

    MacEwan, Joanna P; Forma, Felicia M; Shafrin, Jason; Hatch, Ainslie; Lakdawalla, Darius N; Lindenmayer, Jean-Pierre

    2016-11-01

    Poor medication adherence contributes to negative treatment response, symptom relapse, and hospitalizations in schizophrenia. Many health plans use claims-based measures like medication possession ratios or proportion of days covered (PDC) to measure patient adherence to antipsychotics. Classifying patients solely on the basis of a single average PDC measure, however, may mask clinically meaningful variations over time in how patients arrive at an average PDC level. To model patterns of medication adherence evolving over time for patients with schizophrenia who initiated treatment with an oral atypical antipsychotic and, based on these patterns, to identify groups of patients with different adherence behaviors. We analyzed health insurance claims for patients aged ≥ 18 years with schizophrenia and newly prescribed oral atypical antipsychotics in 2007-2013 from 3 U.S. insurance claims databases: Truven MarketScan (Medicaid and commercial) and Humana (Medicare). Group-based trajectory modeling (GBTM) was used to stratify patients into groups with distinct trends in adherence and to estimate trends for each group. The response variable was the probability of adherence (defined as PDC ≥ 80%) in each 30-day period after the patient initiated antipsychotic therapy. GBTM proceeds from the premise that there are multiple distinct adherence groups. Patient demographics, health status characteristics, and health care resource use metrics were used to identify differences in patient populations across adherence trajectory groups. Among the 29,607 patients who met the inclusion criteria, 6 distinct adherence trajectory groups emerged from the data: adherent (33%); gradual discontinuation after 3 months (15%), 6 months (7%), and 9 months (5%); stop-start after 6 months (15%); and immediate discontinuation (25%). Compared to patients 18-24 years of age in the adherent group, patients displaying a stop-start pattern after 6 months had greater odds of having a history of drug

  12. Determination of antipsychotic drug in human serum by radioreceptor assay

    International Nuclear Information System (INIS)

    Wu Jinchang; Jiang Yimin

    1989-01-01

    Serum antipsychotic drug in 50 psychosis cases were measured by radioreceptor assay (RRA) and the values were compared in parallel with that by radioimmunoassay (RIA). The results showed that the RRA values were lower than the RIA values, but both assays gave significant correlation between the serum drug level and antipsychotic dose

  13. Pharmacokinetic-pharmacodynamic analysis of antipsychotics-induced extrapyramidal symptoms based on receptor occupancy theory incorporating endogenous dopamine release.

    Science.gov (United States)

    Matsui-Sakata, Akiko; Ohtani, Hisakazu; Sawada, Yasufumi

    2005-06-01

    We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

  14. Synthesis and evaluation of a series of 2-substituted-5-thiopropylpiperazine (piperidine)-1,3,4-oxadiazoles derivatives as atypical antipsychotics.

    Science.gov (United States)

    Chen, Yin; Xu, Xiangqing; Liu, Xin; Yu, Minquan; Liu, Bi-Feng; Zhang, Guisen

    2012-01-01

    It is important to develop novel antipsychotics that can effectively treat schizophrenia with minor side-effects. The aim of our work is to develop novel antipsychotics that act on dopamine D(2) and D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors with low affinity for the serotonin 5-HT(2C) and H(1) receptors, which can effectively cure positive symptoms, negative symptoms and cognitive impairment without the weight gain side-effect. A series of 2-substituted-5-thiopropylpiperazine (piperidine) -1,3,4-oxadiazoles derivatives have been synthesized and the target compounds were evaluated for binding affinities to D(2), 5-HT(1A) and 5-HT(2A) receptors. Preliminary results indicated that compounds 14, 16 and 22 exhibited high affinities to D(2), 5-HT(1A) and 5-HT(2A) receptors among these compounds. Further binding tests showed that compound 22 had high affinity for D(3) receptor, and low affinity for serotonin 5-HT(2C) and H(1) receptors. In addition, compound 22 inhibited apomorphine-induced climbing behavior and MK-801-induced hyperactivity with no extrapyramidal symptoms liability in mice. Moreover, compound 22 exhibited acceptable pharmacokinetic properties. Compound 22 showed an atypical antipsychotic activity without liability for extrapyramidal symptoms. We anticipate compound 22 to be useful for developing a novel class of drug for the treatment of schizophrenia.

  15. A bibliometric study of scientific research conducted on second-generation antipsychotic drugs in Singapore.

    Science.gov (United States)

    López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Pérez-Nieto, Miguel Ángel; Alamo, Cecilio

    2014-01-01

    A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors 'atypic* antipsychotic*', 'second-generation antipsychotic*', 'clozapine', 'risperidone', 'olanzapine', 'ziprasidone', 'quetiapine', 'sertindole', 'aripiprazole', 'paliperidone', 'amisulpride', 'zotepine', 'asenapine', 'iloperidone', 'lurasidone', 'perospirone' and 'blonanserin' in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal(4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature.

  16. Antipsychotic drugs a last resort for these 5 conditions (ADHD, Anxiety, Depression, Insomnia and PTSD)

    Science.gov (United States)

    ... more about antipsychotic drugs, see these additional Best Buy Drugs reports. ■ Use of Antipsychotic Drugs in Children ■ Antipsychotic ... depression with antidepressant medication, see our FREE Best Buy Drugs report here . For more about augmentation therapy with ...

  17. Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute major cardiovascular events in young and middle-aged adults

    DEFF Research Database (Denmark)

    Pasternak, Björn; Svanström, Henrik; Ranthe, Mattis F

    2014-01-01

    BACKGROUND: A number of serious cardiovascular safety concerns related to the use of atypical antipsychotics, compared with no use, have emerged, but nearly all reports are from studies of older patients. We aimed to compare the risk of cardiovascular events between the three most commonly used...

  18. Why Research on the Pharmacogenetics of Atypical Antipsychotic-Induced Weight Gain in Individuals with Intellectual Disabilities Is Warranted

    Science.gov (United States)

    Sleister, Heidi M.; Valdovinos, Maria Gabriela

    2011-01-01

    Weight gain is an often-observed side effect of atypical antipsychotics (AAPs) and is particularly significant in individuals with intellectual disabilities (ID). The majority of individuals treated with AAPs will gain at least 10% of their initial body weight over the course of therapy (Umbricht & Kane, 1996). One's genetic constitution is an…

  19. One-year risk of psychiatric hospitalization and associated treatment costs in bipolar disorder treated with atypical antipsychotics: a retrospective claims database analysis

    Directory of Open Access Journals (Sweden)

    Pikalov Andrei

    2011-01-01

    Full Text Available Abstract Background This study compared 1-year risk of psychiatric hospitalization and treatment costs in commercially insured patients with bipolar disorder, treated with aripiprazole, ziprasidone, olanzapine, quetiapine or risperidone. Methods This was a retrospective propensity score-matched cohort study using the Ingenix Lab/Rx integrated insurance claims dataset. Patients with bipolar disorder and 180 days of pre-index enrollment without antipsychotic exposure who received atypical antipsychotic agents were followed for up to 12 months following the initial antipsychotic prescription. The primary analysis used Cox proportional hazards regression to evaluate time-dependent risk of hospitalization, adjusting for age, sex and pre-index hospitalization. Generalized gamma regression compared post-index costs between treatment groups. Results Compared to aripiprazole, ziprasidone, olanzapine and quetiapine had higher risks for hospitalization (hazard ratio 1.96, 1.55 and 1.56, respectively; p Conclusions In commercially insured adults with bipolar disorder followed for 1 year after initiation of atypical antipsychotics, treatment with aripiprazole was associated with a lower risk of psychiatric hospitalization than ziprasidone, quetiapine, olanzapine and risperidone, although this did not reach significance with the latter. Aripiprazole was also associated with significantly lower total healthcare costs than quetiapine, but not the other comparators.

  20. Quetiapine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; Srisurapanont, Manit; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (’atypical’) antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ. Objectives To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. Selection criteria We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone. A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear

  1. Mental disorder diagnoses among children and adolescents who use antipsychotic drugs.

    Science.gov (United States)

    Nesvåg, Ragnar; Hartz, Ingeborg; Bramness, Jørgen G; Hjellvik, Vidar; Handal, Marte; Skurtveit, Svetlana

    2016-09-01

    Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  2. [Lipid spectrum changes and ECG in patients with paranoid schizophrenia in the course of therapy with atypical antipsychotics].

    Science.gov (United States)

    Smirnova, L P; Parshukova, D A; Borodyuk, Yu N; Kornetova, E G; Tkacheva, G D; Seregin, A A; Burdovitsina, T G; Semke, A V

    2015-01-01

    To study correlations between parameters of lipid metabolism and ECG in patients with schizophrenia in light of therapy with atypical antipsychotics. We examined 42 patients with paranoid schizophrenia. All patients received atypical neuroleptics - seroquel, zyprexa, and rispolept. A group of controls included 25 healthy people. There was a significant increase (p=0.0002) in body mass (in average by 1.5 kg) in 88% patients. A significant increase in the concentration of serum triglycerides was identified as well. The concentration of VLDL in the patients with schizophrenia was 2 times higher compared to controls. After treatment, VLDL concentration increased even more considerably An increase in atherogenic index (AI) was up to 3.1 in patients with schizophrenia compared to 2.2 in controls. After treatment, Al increased up to 4 that demonstrated the high risk of development of atherosclerosis. A significant increase in QT interval in the ECG and heart rate (p=0.03) was revealed only in patients receiving rispolept. In patients receiving zyprexa and seroquel only heart rate was increased. The antipsychotics studied increase the risk of development of cardiovascular pathology.

  3. Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia

    DEFF Research Database (Denmark)

    Zakarias, Johanne Købstrup; Jensen-Dahm, Christina; Nørgaard, Ane

    2016-01-01

    BACKGROUND: Use of antipsychotics in elderly patients with dementia has decreased in the past decade due to safety regulations; however use is still high. Geographical variation may indicate discrepancies in clinical practice and lack of adherence to evidence-based guidelines for the management...... of behavioral symptoms. OBJECTIVE: To investigate potential geographical variances in use of antipsychotic drugs in dementia care. METHODS: A registry-based cross-sectional study in the entire elderly population of Denmark (≥65 years) conducted in 2012. Data included place of residence, prescriptions filled......, and hospital discharge diagnoses. Antipsychotic drug use among elderly with (n = 34,536) and without (n = 931,203) a dementia diagnosis was compared across the five regions and 98 municipalities in Denmark, adjusted for age and sex. RESULTS: In 2012, the national prevalence of antipsychotic drug use was 20...

  4. Association between P-glycoprotein polymorphisms and antipsychotic drug-induced hyperprolactinemia

    NARCIS (Netherlands)

    Geers, Lisanne; Pozhidaev, Ivan V; Ivanova, Svetlana A.; Freidin, Maxim B.; Cohen, Dan; Boiko, Anastasia S; Osmanova, Diana Z; Fedorenko, Olga Yu; Touw, Daniël; Semke, Arkadiy V.; Wilffert, Berend; Bokhan, Nikolay A.; Loonen, Antonius

    2017-01-01

    Background: Regular therapy for schizophrenia includes maintenance antipsychotic treatment. Unfortunately, antipsychotics also have a spectrum of side effects, including metabolic, endocrine, cardiovascular, and movement disorders. One of the common side effects of these drugs is hyperprolactinemia

  5. Synthesis and evaluation of a series of 2-substituted-5-thiopropylpiperazine (piperidine-1,3,4-oxadiazoles derivatives as atypical antipsychotics.

    Directory of Open Access Journals (Sweden)

    Yin Chen

    Full Text Available BACKGROUND: It is important to develop novel antipsychotics that can effectively treat schizophrenia with minor side-effects. The aim of our work is to develop novel antipsychotics that act on dopamine D(2 and D(3, serotonin 5-HT(1A and 5-HT(2A receptors with low affinity for the serotonin 5-HT(2C and H(1 receptors, which can effectively cure positive symptoms, negative symptoms and cognitive impairment without the weight gain side-effect. METHODOLOGY/PRINCIPAL FINDINGS: A series of 2-substituted-5-thiopropylpiperazine (piperidine -1,3,4-oxadiazoles derivatives have been synthesized and the target compounds were evaluated for binding affinities to D(2, 5-HT(1A and 5-HT(2A receptors. Preliminary results indicated that compounds 14, 16 and 22 exhibited high affinities to D(2, 5-HT(1A and 5-HT(2A receptors among these compounds. Further binding tests showed that compound 22 had high affinity for D(3 receptor, and low affinity for serotonin 5-HT(2C and H(1 receptors. In addition, compound 22 inhibited apomorphine-induced climbing behavior and MK-801-induced hyperactivity with no extrapyramidal symptoms liability in mice. Moreover, compound 22 exhibited acceptable pharmacokinetic properties. CONCLUSIONS/SIGNIFICANCE: Compound 22 showed an atypical antipsychotic activity without liability for extrapyramidal symptoms. We anticipate compound 22 to be useful for developing a novel class of drug for the treatment of schizophrenia.

  6. [Initial experiences with amisulpride, an in Germany novel, atypical neuroleptic drug in treatment of adolescents with psychiatric disorders].

    Science.gov (United States)

    Göpel, C; Marcus, A

    2001-08-01

    In addition to conventional antipsychotic drugs, during the past decade an increasing number of atypical neuroleptics has been introduced in the treatment of juvenile schizophrenic and schizoaffective disorders. In 1999 Germany legalized the benzamide amisulpride for the treatment of acute and chronic schizophrenic symptoms. Preliminary treatment results are reported here. Ten adolescent cases are presented with regard to the efficacy, side effects and dosage of amisulpride. Preliminary results on the use of amisulpride are promising. The rate of side effects is tolerable. Amisulprise seems to constitute a useful alternative in the treatment of juvenile schizophrenia for those who suffer from intolerable side effects of classical or atypical neuroleptics. Controlled studies are warranted to further clarify its efficacy and safety in the treatment of adolescents.

  7. Time Trends in Antipsychotic Drug Use in Patients with Dementia

    DEFF Research Database (Denmark)

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane

    2015-01-01

    : To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...

  8. Models of treatment with antipsychotics of the schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Svjetlana Loga-Zec

    2005-11-01

    Full Text Available The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration, especially with antiparkinsonics. The research (study is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg, not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as

  9. Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: relationship with stearoyl-CoA desaturase activity.

    Science.gov (United States)

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W

    2011-06-01

    Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6mg/kg/d), paliperidone (1.5, 3, and 6mg/kg/d), olanzapine (2.5, 5, and 10mg/kg/d), quetiapine (5, 10, and 20mg/kg/d), haloperidol (1, and 3mg/kg/d) or vehicle through their drinking water for 40days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, 'desaturation index') were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n=122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Off-label use of atypical antipsychotics: cause for concern?

    Science.gov (United States)

    McKean, Andrew; Monasterio, Erik

    2012-05-01

    Licensed indications for medicines were designed to regulate the claims that can be made about a medicine by a pharmaceutical company. Off-label prescribing (i.e. prescribing a drug for an indication outside of that for which it is licensed) is legal and an integral part of medical practice. In psychiatry, off-label prescribing is common and gives clinicians scope to treat patients who are refractory to standard therapy or where there is no licensed medication for an indication. However, efficacy or safety of such off-label use may not be established. There is a growing list of licensed indications for atypical antipsychotics (AAP) beyond schizophrenia and bipolar affective disorder, and also more evidence for other indications where pharmaceutical companies have not obtained a license. Pharmaceutical companies have promoted AAPs for off-label indications to increase sales and consequently have been fined by the US FDA for this. Since the 1990s, AAP use has expanded considerably, for example, the off-label use of quetiapine alone accounted for an estimated 17% of the AAP spend in New Zealand in 2010. There are a number of potential problems with the expanded use of AAPs outside of schizophrenia and related psychoses. A larger population will be exposed to their adverse effects, which include weight gain, type 2 diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. There are also concerns with the abuse of these agents, in particular quetiapine. Given that an increasing percentage of the population is being treated with these agents, off-label prescribing of AAPs is a cause for concern; they have a propensity to cause significant side effects and their efficacy and long-term safety for most off-label indications remains largely unknown, and therefore the risks and benefits of their use should be carefully weighed up prior to prescribing these agents off-label.

  11. Prevalence of concurrent use of antipsychotic drugs and herbal ...

    African Journals Online (AJOL)

    The use of herbal medicines with conventional medicines is on the rise. Therefore, drug-herb interactions have become an important issue in drug safety and efficacy in clinical practice. A cross-sectional prospective study using a structured questionnaire was carried out on patients using antipsychotic drugs attending the ...

  12. Sex differences in the subjective tolerability of antipsychotic drugs

    NARCIS (Netherlands)

    Barbui, Corrado; Nosè, Michela; Bindman, Jonathan; Schene, Aart; Becker, Thomas; Mazzi, Maria A.; Kikkert, Martijn; Camara, Jayne; Born, Anja; Tansella, Michele

    2005-01-01

    In recent years, research efforts have been directed to better characterize the Subjective experience of taking psychotropic drugs. This Study investigated the sex difference in the subjective tolerability of antipsychotic drugs. Participants were recruited from patients under the care of

  13. Handwriting Movement Kinematics for Quantifying EPS in Patients Treated with Atypical Antipsychotics

    Science.gov (United States)

    Caligiuri, Michael P.; Teulings, Hans-Leo; Dean, Charles E.; Niculescu, Alexander B.; Lohr, James B.

    2009-01-01

    Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system. PMID:20381875

  14. Toward an understanding of antipsychotic drug induced weight gain - use of a rodent model

    OpenAIRE

    Stefanidis, Aneta

    2017-01-01

    Antipsychotic drug therapy is a fundamental tool in the treatment of schizophrenia and other psychoses. Recent years have seen the development of new antipsychotic compounds with an improved acute adverse effect profile; however these are often associated with weight gain and increased risk of metabolic disturbances. Olanzapine, despite its considerable adverse impact on weight gain and associated pathologies, has been recognized as the most efficacious antipsychotic drug in the treatment of ...

  15. A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice

    Directory of Open Access Journals (Sweden)

    Bodén R

    2013-03-01

    Full Text Available Robert Bodén,1,2 Gunnar Edman,3,4 Johan Reutfors,2 Claes-Göran Östenson,3 Urban Ösby3,4 1Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden; 2Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 4Department of Psychiatry, Tiohundra AB, Norrtälje, Sweden Abstract: It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08–3.04, reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01–2.97; and OR = 2.03, 95% CI 1.32–3.13, hypertension with perphenazine (OR = 2.00, 95% CI 1.21–3.59, and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05–0.89 and positively with haloperidol (OR = 2.02, 95% CI 1.18–3.48. There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In

  16. Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.

    Directory of Open Access Journals (Sweden)

    Kensuke Sakuma

    Full Text Available Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs, raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR. Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist, olanzapine (antagonist, and aripiprazole (partial agonist all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.

  17. Antipsychotic adjunctive therapy to mood stabilizers and 1-year rehospitalization rates in bipolar disorder: A cohort study.

    Science.gov (United States)

    Hochman, Eldar; Krivoy, Amir; Schaffer, Ayal; Weizman, Abraham; Valevski, Avi

    2016-12-01

    Antipsychotic adjunctive therapy to mood stabilizers (MSs) may improve relapse prevention; however, only a few naturalistic studies, reflecting more generalizable bipolar disorder (BD) samples, support this notion. We compared the 1-year rehospitalization rates of manic patients with bipolar I disorder (BD-I) who were discharged with MS (lithium or valproate) monotherapy or with adjunctive atypical or typical antipsychotic therapy. A total of 201 patients with BD-I who were hospitalized with manic episodes between 2005 and 2013 were retrospectively followed for 1-year rehospitalization rates according to treatment at discharge: MS monotherapy, MS with atypical antipsychotics, and MS with typical antipsychotics. Additionally, time to rehospitalization during the 1-year period after discharge was compared between treatment groups. Multivariable survival analyses adjusted for covariates known to influence rehospitalization were conducted. Rehospitalization rates within 1 year were significantly lower in the MS with atypical antipsychotics group (6.3%) compared to the MS monotherapy group (24.3%, P=.008) and to the MS with typical antipsychotics group (20.6%, P=.02). Time to rehospitalization was significantly longer for the MS with atypical antipsychotics group (345.5 days) compared to the MS monotherapy group (315.1 days, P=.006) and to the MS with typical antipsychotics group (334.1 days, P=.02). The MS with atypical antipsychotics group had a significantly reduced adjusted risk of rehospitalization (hazard ratio=0.17, 95% confidence interval: 0.05-0.61, P=.007) compared to the MS monotherapy group. Atypical antipsychotic adjunctive therapy to MSs may be more effective than MS monotherapy in preventing rehospitalization during the 1-year period after a BD manic episode. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    Directory of Open Access Journals (Sweden)

    Quevedo-Florez Leonardo

    2017-01-01

    Full Text Available The Neuroleptic Malignant Syndrome (NMS is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

  19. Pharmacogenetics and outcome with antipsychotic drugs.

    Science.gov (United States)

    Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

    2014-12-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

  20. Adjunctive Treatment of Acute Mania with Risperidone versus Typical Antipsychotics: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Jui-Hsiu Tsai

    2005-12-01

    Full Text Available Few studies have directly compared atypical antipsychotics (e.g. risperidone with typical antipsychotics as adjunctive therapy in patients hospitalized for acute mania, especially during a lengthy hospital stay. Our retrospective, case-controlled study is a chart review of 64 patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, defined bipolar I disorder (current episode, mania. Patients were divided into two groups according to the adjunctive medications used: the risperidone group (mood stabilizers plus risperidone and the control group (mood stabilizers plus typical antipsychotics. Outcome at discharge, medications, adverse drug effects, and length of hospital stay were compared between groups, controlling for gender, age, number of prior admissions, and duration of illness. Results indicated no statistically significant differences between groups in the controlled factors, Global Assessment of Functioning and Clinical Global Impression-Improvement scores, and adverse drug events. Patients in the risperidone group used significantly lower doses of trihexyphenidyl than those in the control group (p < 0.05. Patients treated with risperidone had a shorter hospital stay than those treated with typical antipsychotics (p < 0.01. In conclusion, antipsychotics are effective as adjunctive agents in the treatment of acute mania. The use of risperidone, in particular, decreases the need for anticholinergics and may lead to a shorter hospital stay compared with typical antipsychotics.

  1. Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

    DEFF Research Database (Denmark)

    Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

    2015-01-01

    limited experimental information exists about the effects of α1-adrenergic receptor activity of antipsychotic drugs in pro-arrhythmic models, we have decided to investigate this. In this study we show that four antipsychotic drugs all have high affinity for α1-adrenergic receptor (sertindole>risperidone>haloperidol......>olanzapine) and all block IKr (sertindole>haloperidol>risperidone>olanzapine). In canine Purkinje fibres, α1-adrenergic stimulation prolonged action potential duration; however, the stimulation does not cause afterdepolarizations, even in the presence of dofetilide-induced delayed repolarization. We showed...

  2. [Conference report: Belgian consensus on metabolic problems associated with atypical antipsychotics].

    Science.gov (United States)

    De Nayer, A; De Hert, M; Scheen, A; Van Gaal, L; Peuskens, J

    2007-01-01

    The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. As a consequence, there is a shift in attention toward physical health

  3. Relationship between antipsychotic medication, obesity and cognitive functions

    Directory of Open Access Journals (Sweden)

    Łopuszańska Urszula

    2017-12-01

    Full Text Available Introduction: The purpose of this study was to examine whether the combination of atypical and typical antipsychotic medications is related with metabolism and cognitive functions in the same manner and degree as taking medications of one kind only, i.e. atypical or typical.

  4. Off-label utilization of antipsychotics | Zullino | African Journal of ...

    African Journals Online (AJOL)

    Objective: The newer atypical antipsychotics are prescribed because of their enhanced safety profiles and their larger pharmacological profile in comparison to the conventional antipsychotics. This has led to broad off-label utilisation. The aim of the present survey was to study the prescribing practice of hospital psychiatrists ...

  5. [Informed Consent and the Approval by Ethics Committees of Studies Involving the Use of Atypical Antipsychotics in the Management of Delirium].

    Science.gov (United States)

    Millán-González, Ricardo

    2012-03-01

    Delirium is an acute alteration of consciousness and cognition. Atypical antipsychotics (AA) have recently become a main part of its treatment. Studies in this population generate a series of ethical dilemmas concerning the voluntary participation of patients and their state of vulnerability since their mental faculties are, by definition, compromised. To assess whether studies with AA for the treatment of delirium obtained an approval by an ethics committee on human research (ECHR), if an informed consent (IC) was obtained, whether the IC was verbal or written, and who gave the approval to participate. Systematic review of Medline for studies of delirium where quetiapine and olanzapine were the main treatment, assessing the existence of an ECHR approval and implementation of an IC. 11 studies were identified (6 of quetiapine and 5 of olanzapine). 5 had an ECHR approval. Most studies examining the treatment of delirium with quetiapine or olanzapine were not subject to approval by an ECHR and most of them did not obtain an IC from the patient's legal guardian. It is essential that future studies of antipsychotics and other drugs for the treatment of delirium have the protocol approved by an ECHR and a written IC signed by the patient's legal representative, since by definition delirium is a condition that compromises superior mental processes. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  6. Positive predictive value of automated database records for diabetic ketoacidosis (DKA in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study

    Directory of Open Access Journals (Sweden)

    Bobo William V

    2011-11-01

    Full Text Available Abstract Background Diabetic ketoacidosis (DKA is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and youth. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard." Methods The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007 in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1 were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA. Results Of 30 potential cases, 27 (90% were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%. Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis. Conclusions Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.

  7. Antipsychotic prescription in children and adolescents: an analysis of data from a German statutory health insurance company from 2005 to 2012.

    Science.gov (United States)

    Bachmann, Christian J; Lempp, Thomas; Glaeske, Gerd; Hoffmann, Falk

    2014-01-17

    Despite sparse documentation of their long-term therapeutic effects and side effects, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in recent years, both in the USA and in Europe. No current data are available about antipsychotic prescriptions for this age group in Germany. Data from the largest statutory health insurance fund in Germany (BARMER GEK) were studied to identify antipsychotic prescriptions for children and adolescents (age 0-19 years) from 2005 to 2012 and analyze them with respect to age, sex, drug prescribed, prescribing medical specialty, and any observable secular trends. The percentage of children and adolescents receiving a prescription for an antipsychotic drug rose from 0.23% in 2005 to 0.32% in 2012. In particular, atypical antipsychotic drugs were prescribed more frequently over time (from 0.10% in 2005 to 0.24% in 2012). The rise in antipsychotic prescriptions was particularly marked among 10- to 14-year-olds (from 0.24% to 0.43%) and among 15- to 19-year-olds (from 0.34% to 0.54%). The prescribing physicians were mostly either child and adolescent psychiatrists or pediatricians; the most commonly prescribed drugs were risperidone and pipamperone. Risperidone was most commonly prescribed for patients with hyperkinetic disorders and conduct disorders. In Germany as in other industrialized countries, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in ecent years. The German figures, while still lower than those from North America, are in the middle range of figures from European countries. The causes of the increase should be critically examined; if appropriate, the introduction of prescribing guidelines of a more restrictive nature could be considered.

  8. Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia.

    Science.gov (United States)

    Tomelleri, Luisa; Jogia, Jigar; Perlini, Cinzia; Bellani, Marcella; Ferro, Adele; Rambaldelli, Gianluca; Tansella, Michele; Frangou, Sophia; Brambilla, Paolo

    2009-12-01

    Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology.

  9. Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

    Science.gov (United States)

    Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

  10. Analysis of clinical characteristics and antipsychotic medication prescribing practices of first-episode schizophrenia in Israel: a naturalistic prospective study.

    Science.gov (United States)

    Strous, Rael D; Bar, Faina; Keret, Noa; Lapidus, Raya; Kosov, Nikolai; Chelben, Joseph; Kotler, Moshe

    2006-01-01

    Investigation of the clinical presentation and treatment of first-episode psychosis is important in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. The aim of this descriptive study was to investigate the management practices of first-episode schizophrenia in a cohort of patients in Israel and to document use of the various "typical" or "atypical" antipsychotic agents. Fifty-one consecutive patients (26 M, 25 F) with first-episode psychosis were recruited for study participation and were administered either typical or atypical antipsychotic medications in a naturalistic manner. While an approximately equal number of subjects received typical and atypical medications at illness onset, a prominent shift to atypical antipsychotic treatment occurred over the study course; 18 subjects had medication class shifts: 17 from typical to atypical, and one from atypical to typical. Negative symptoms did not affect length of hospitalization, but were associated with aggression. Higher depression rates were noted in patients with long hospitalizations who received typical antipsychotic medications. Immigrants were admitted at an age approximately four years older than native-born Israelis. The prominent shift from "typical" to "atypical" antipsychotic medications may indicate sensitivity of first-episode psychotic patients to side-effects of "typical" medications and prominence of use of atypical medications in this patient subpopulation be it due to improved efficacy over time or successful marketing. Unique cultural and population characteristics may contribute to the manifestation of first-episode psychosis and suggest the importance of more effective outreach to the immigrant population in order to manage an apparent treatment delay.

  11. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Vik-Mo Audun O

    2006-10-01

    Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

  12. Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN

    Directory of Open Access Journals (Sweden)

    Margaret E. Mattson

    2015-01-01

    Full Text Available Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional. Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN for prevalence of emergency department (ED visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA.

  13. Use of antipsychotic drugs in individuals with intellectual disability (ID) in the Netherlands : prevalence and reasons for prescription

    NARCIS (Netherlands)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    Background We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods A cross-sectional study of medical and pharmaceutical

  14. Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia.

    Science.gov (United States)

    Sumiyoshi, Tomiki; Tsunoda, Masahiko; Higuchi, Yuko; Itoh, Toru; Seo, Tomonori; Itoh, Hiroko; Suzuki, Michio; Kurachi, Masayoshi

    2010-05-01

    The purpose of this study was to determine if the functional single nucleotide polymorphisms of rs6259 C(-1019)G in the promoter region, which regulates serotonin 5-HT(1A) receptor transcription, affects the ability of antipsychotic drugs to improve attention in patients with schizophrenia. Subjects were neuroleptic-free and meeting DSM-IV-TR criteria for schizophrenia. Psychopathology and attention were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline and 3 months after treatment with atypical antipsychotic drugs (AAPDs). DNA was extracted from peripheral blood following standard procedures. Genotyping was performed with HS-Taq assay (LaboPass). Data were available from 30 subjects (male/female=19/11), in which 17 had the CC genotype, three had the GG genotype, and 10 were heterozygous. The 3-month treatment with AAPDs was associated with significant improvements in positive and negative symptoms, but not attention as measured by SANS-Attention subscale in the entire subject group. There were no significant differences in the degree of improvements of SAPS and SANS scores between the CC genotype group and the (C/G plus G/G) combined group. On the other hand, improvement of attention was significantly greater for the former group compared to the latter group (P<0.016), suggesting a detrimental influence of the G-allele. These results provide additional support to the role of 5-HT(1A) receptors in some of the cognitive disturbances of schizophrenia. Further studies with a larger number of subjects are warranted.

  15. Atypical antipsychotics: recent research findings and applications to clinical practice: Proceedings of a symposium presented at the 29th Annual European College of Neuropsychopharmacology Congress, 19 September 2016, Vienna, Austria.

    Science.gov (United States)

    Murray, Robin; Correll, Christoph U; Reynolds, Gavin P; Taylor, David

    2017-03-01

    Available evidence suggests that second-generation atypical antipsychotics are broadly similar to first-generation agents in terms of their efficacy, but may have a more favourable tolerability profile, primarily by being less likely to cause extrapyramidal symptoms. However, atypical antipsychotics are variably associated with disturbances in the cardiometabolic arena, including increased body weight and the development of metabolic syndrome, which may reflect differences in their receptor binding profiles. Effective management of schizophrenia must ensure that the physical health of patients is addressed together with their mental health. This should therefore involve consideration of the specific tolerability profiles of available agents and individualization of treatment to minimize the likelihood of adverse metabolic sequelae, thereby improving long-term adherence and optimizing overall treatment outcomes. Alongside this, modifiable risk factors (such as exercise, diet, obesity/body weight and smoking status) must be addressed, in order to optimize patients' overall health and quality of life (QoL). In addition to antipsychotic-induced side effects, the clinical management of early nonresponders and psychopharmacological approaches for patients with treatment-resistant schizophrenia remain important unmet needs. Evidence suggests that antipsychotic response starts early in the course of treatment and that early nonresponse accurately predicts nonresponse over the longer term. Early nonresponse therefore represents an important modifiable risk factor for poor efficacy and effectiveness outcomes, since switching or augmenting antipsychotic treatment in patients showing early nonresponse has been shown to improve the likelihood of subsequent treatment outcomes. Recent evidence has also demonstrated that patients showing early nonresponse to treatment with lurasidone at 2 weeks may benefit from an increase in dose at this timepoint without compromising

  16. Manual or automated measuring of antipsychotics' chemical oxygen demand.

    Science.gov (United States)

    Pereira, Sarah A P; Costa, Susana P F; Cunha, Edite; Passos, Marieta L C; Araújo, André R S T; Saraiva, M Lúcia M F S

    2018-05-15

    Antipsychotic (AP) drugs are becoming accumulated in terrestrial and aqueous resources due to their actual consumption. Thus, the search of methods for assessing the contamination load of these drugs is mandatory. The COD is a key parameter used for monitoring water quality upon the assessment of the effect of polluting agents on the oxygen level. Thus, the present work aims to assess the chemical oxygen demand (COD) levels of several typical and atypical antipsychotic drugs in order to obtain structure-activity relationships. It was implemented the titrimetric method with potassium dichromate as oxidant and a digestion step of 2h, followed by the measurement of remained unreduced dichromate by titration. After that, an automated sequential injection analysis (SIA) method was, also, used aiming to overcome some drawbacks of the titrimetric method. The results obtained showed a relationship between the chemical structures of antipsychotic drugs and their COD values, where the presence of aromatic rings and oxidable groups give higher COD values. It was obtained a good compliance between the results of the reference batch procedure and the SIA system, and the APs were clustered in two groups, with the values ratio between the methodologies, of 2 or 4, in the case of lower or higher COD values, respectively. The SIA methodology is capable of operating as a screening method, in any stage of a synthetic process, being also more environmentally friendly, and cost-effective. Besides, the studies presented open promising perspectives for the improvement of the effectiveness of pharmaceutical removal from the waste effluents, by assessing COD values. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

    DEFF Research Database (Denmark)

    Nielsen, R E; Lolk, A; Valentin, J B

    2016-01-01

    OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort...... study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased...... or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs...

  18. Antipsychotics and amotivation.

    Science.gov (United States)

    Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

    2015-05-01

    Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.

  19. Use of Antipsychotic Drugs in Individuals with Intellectual Disability (ID) in the Netherlands: Prevalence and Reasons for Prescription

    Science.gov (United States)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    2010-01-01

    Background: We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods: A cross-sectional study of medical and pharmaceutical records in a population living in residential…

  20. Lurasidone-β-cyclodextrin complexes: Physicochemical characterization and comparison of their antidepressant, antipsychotic activities against that of self microemulsifying formulation

    Science.gov (United States)

    Londhe, Vaishali Y.; Deshmane, Aishwarya B.; Singh, Sarita R.; Kulkarni, Yogesh A.

    2018-04-01

    Lurasidone hydrochloride (LHD) is an atypical antipsychotic drug has poor aqueous solubility and low bioavailability (9-19%). This study describes effect of different methods of complex formation with β-cyclodextrin (BCD) on enhancement of dissolution and on antidepressant, antipsychotic effects of LHD. Other purpose of this study is to compare pharmacodynamic effects of complexes with that of self microemulsifying drug delivery system of LHD (SMEDDS). Inclusion complexes (IC) of LHD and BCD were prepared by physical mixing (PM), kneading (KN) and spray drying (SD) in a 1:1 M ratio. These complexes were characterized by different techniques. KN and SD showing enhancement in dissolution, were compared with SMEDDS using Forced swim test (FST) and Tail suspension test (TST) for antidepressant action and Paw test for antipsychotic activity. Characterization of complexes confirmed interaction between LHD and BCD. Enhancement in dissolution is seen in following order SD > KN > PM > LHD. In all three animal models, SD, KN and SMEDDS showed statistically significant effect (p LHD.

  1. Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling

    DEFF Research Database (Denmark)

    Klewe, Ib V; Nielsen, Søren M; Tarpø, Louise

    2008-01-01

    , SNPA all acted as partial agonists with decreasing efficacy in the BRET assay. In contrast, a wide selection of typical and atypical anti-psychotics was incapable of stimulating beta-arrestin2 recruitment to the D2 receptor. Moreover, we observed that haloperidol, sertindole, olanzapine, clozapine...

  2. Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Stella de Azevedo Silveira

    2015-12-01

    Full Text Available Abstract Background Despite of its global underuse, clozapine is still the golden standard antipsychotic for patients with treatment-resistant schizophrenia (TRS. Objective To evaluate the patterns of clozapine and other antipsychotic drugs prescription in TRS in community mental health centers in São Paulo, Brazil. Methods A multiple-choice questionnaire was applied to fifteen psychiatrists at five centers inquiring about patients’ clinical condition, adherence to oral treatment and current antipsychotic treatment. History of previous and current antipsychotic treatment was collected through medical chart review. Results Out of 442 schizophrenia patients, 103 (23.3% fulfilled the criteria for TRS. Fifty-eight patients (56.3% were receiving polypharmacy; 30 (29.1% were on atypical antipsychotic monotherapy, 14 (13.6% were on typical antipsychotic monotherapy, 25 (24.3% were taking depot antipsychotic medication and only 22 (21.4% were receiving clozapine. Discussion As well as in other parts of the world, many TRS patients (78.6% receive other drugs instead of clozapine in São Paulo, the best evidence-based medication for patients with TRS. The government should make every effort to provide medical training and the equipment and logistic support to adequately serve those who could benefit from clozapine treatment at the community health centers.

  3. Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

    Science.gov (United States)

    Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

    2017-08-03

    To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, pmovement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Quality of life and response of negative symptoms in schizophrenia to haloperidol and the atypical antipsychotic remoxipride. The Canadian Remoxipride Group.

    Science.gov (United States)

    Awad, A G; Lapierre, Y D; Angus, C; Rylander, A

    1997-07-01

    In a large, multicenter, double-blind study of the effect of haloperidol and the atypical antipsychotic remoxipride on improvement of negative symptoms in schizophrenia, quality of life was also assessed using a modified version of the Sickness Impact Profile (SIP). Compared with previous studies, this study had a longer duration (28 weeks), and the dose of the comparator, haloperidol, was much lower. At the end of the study, compared with the baseline, both treatment groups reported comparable improvement in negative symptoms as defined by the protocol (at least 20% improvement). Similarly, both groups showed comparable changes on global and multidimensional self-assessments of quality of life. All the subfactors of the modified version of the SIP were similar in both groups, except for the subfactor that relates to alertness behavior, which possibly reflects remoxipride's lack of any sedating properties compared with haloperidol. This study presents an approach for inclusion of quality of life as an outcome measure in the design of clinical trials of new antipsychotic medications.

  5. Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

    DEFF Research Database (Denmark)

    Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang

    2012-01-01

    Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

  6. Antipsychotic drug prescription rates among Dutch nursing homes : the influence of patient characteristics and the dementia special care unit

    NARCIS (Netherlands)

    van der Putten, M. J. G.; Wetzels, R. B.; Bor, H.; Zuidema, S. U.; Koopmans, R. T. C. M.

    2014-01-01

    Objectives: To assess the differences in antipsychotic drug prescription rates in residents with dementia in dementia special care units (SCUs) of Dutch nursing homes, considering the differences in patient characteristics. Method: As part of the Waalbed-II study, the data on antipsychotic drug use

  7. Can a digital medicine system improve adherence to antipsychotic treatment?

    Science.gov (United States)

    Papola, D; Gastaldon, C; Ostuzzi, G

    2018-06-01

    A substantial proportion of people with mental health conditions do not adhere to prescribed pharmacological treatments. Poor adherence is probably one of the most critical elements contributing to relapse in people with schizophrenia and other severe mental disorders. In order to tackle this global issue, in November 2017 the Food and Drug Administration approved a tablet formulation of the atypical antipsychotic aripiprazole embedded with a novel digital adherence-assessment device. In this commentary, we critically appraised the potential beneficial and harmful consequences of this new digital formulation of aripiprazole, and we highlighted expected implications for clinical practice.

  8. Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics.

    Science.gov (United States)

    Lan, T H; Loh, E W; Wu, M S; Hu, T M; Chou, P; Lan, T Y; Chiu, H-J

    2008-12-01

    Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neuro-fuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.

  9. Continuous, but not intermittent, antipsychotic drug delivery intensifies the pursuit of reward cues.

    Science.gov (United States)

    Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

    2011-05-01

    Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

  10. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs.

    Science.gov (United States)

    Nordon, Clementine; Battin, Constance; Verdoux, Helene; Haro, Josef Maria; Belger, Mark; Abenhaim, Lucien; van Staa, Tjeerd Pieter

    2017-01-01

    A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level. Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist's gender, age, length of practice experience, practice setting and type, countries' Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1) to estimate antipsychotic drugs' effectiveness (defined as the association between patients' outcome at 3 months - dependent variable, continuous - and antipsychotic drug initiation at baseline - drug A vs other antipsychotic drug); 2) to estimate the similarity between clustered data (using the intra-cluster correlation coefficient); and 3) to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term). About 23% of the variance found for patients' outcome was explained by unmeasured confounding at a center level. Psychiatrists' practice experience was found to be associated with patient outcomes ( p =0.04) and modified the relative effect of "drug A" ( p <0.001), independent of center- or patient-related characteristics. Mixed models may be useful to explore how center-related characteristics modify drugs' effect estimates, but require numerous assumptions.

  11. Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Spoelstra, JA; Stolk, RP; Cohen, D; Klungel, OH; Erkens, JA; Leufkens, HGM; Grobbee, DE

    (B)ackground: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. Method: In

  12. Challenges and opportunities for the development of new antipsychotic drugs.

    Science.gov (United States)

    Forray, Carlos; Buller, Raimund

    2017-11-01

    In spite of the significant impact that the serendipitous discovery of drugs with antipsychotic properties had on the care of patients with psychotic disorders, there are significant challenges when aiming at therapeutic goals such as remission, recovery, improved health-related quality of life and functioning. The efficacy and effectiveness of existing antipsychotic drugs fail to address the full spectrum of symptoms and functional deficits that currently prevent patients with psychotic disorders from achieving fulfilling lives. The study of the pharmacological mechanism of action has increased our knowledge on molecular targets and brain circuits related to the antipsychotic properties of this drug class. However, our understanding of how these molecular targets and brain circuits relate to other aspects of disease pathophysiology like cognitive impairment and negative symptoms is incomplete although these are significant clinical unmet needs. Currently, there is still an important knowledge gap between psychopathology and pathophysiology in schizophrenia research. This may have contributed to some recent costly failures of large clinical development programs for drugs targeted at glutamatergic function and nicotinic receptors. The lack of success of these pharmacological approaches to achieve clinical validation raises important questions concerning the underlying hypothesis that guided the choice of molecular targets, and about the predictive validity of translational models that supported the rationale for testing these drugs in clinical studies. From a clinical perspective there is a need to more strongly consider the disease heterogeneity linked to the use of the current diagnostic classification of subjects and to the validity of the psychopathological constructs and assessments that are used to assess clinical outcomes. A paradigm shift in the development of drugs for schizophrenia is needed. This will require among other addressing: the shortcomings of a

  13. Fluvoxamine for blonanserin-associated akathisia in patients with schizophrenia: report of five cases

    Directory of Open Access Journals (Sweden)

    Hashimoto Kenji

    2010-04-01

    Full Text Available Abstract Background Atypical antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPS than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interaction of several neurotransmitter systems plays a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors have been shown to regulate a number of neurotransmitter systems in the brain. Methods We report on five cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the new atypical antipsychotic drug blonanserin. Results The global score on the Barnes Akathisia Scale in five patients with schizophrenia treated with blonanserin rapidly decreased after fluvoxamine treatment. Conclusion Doctors should consider that fluvoxamine may be an alternative approach in treating akathisia associated with atypical antipsychotic drugs.

  14. Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics.

    Science.gov (United States)

    Remenar, Julius F

    2014-06-02

    There are now long-acting versions of six antipsychotic drugs on the U.S. market, and with them, five unique combinations of molecular form and delivery strategy long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses of schizophrenia, but their introduction has been slow, taking at least nine years after the approval of each oral drug. Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables (LAIs). This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include (1) the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and (2) the role of physiological responses at the injection site in the release of drug from a depot.

  15. Association between Ghrelin gene (GHRL polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Yang Yongfeng

    2012-02-01

    Full Text Available Abstract Background Ghrelin (GHRL is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG is a common side effect of the atypical antipsychotics (AAPs used to treat schizophrenia (SZ. Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI. However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Methods Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C were genotyped in 634 schizophrenia patients and 606 control subjects. Results There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05. There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS. However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P P Conclusions These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

  16. Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients.

    Science.gov (United States)

    Yang, Yongfeng; Li, Wenqiang; Zhao, Jingyuan; Zhang, Hongxing; Song, Xueqin; Xiao, Bo; Yang, Ge; Jiang, Chengdi; Zhang, Dai; Yue, Weihua; Lv, Luxian

    2012-02-28

    Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

  17. Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation.

    Directory of Open Access Journals (Sweden)

    Feng Mei

    Full Text Available Quetiapine (Que, a commonly used atypical antipsychotic drug (APD, can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS, an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells. In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE, a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55 peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+/CD8(+ populations and the proliferation of effector T cells (CD4(+CD25(- in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+/CD8(+ T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+/CD8(+ T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55 or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+CD25(- isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.

  18. Drug-Refractory Aggression, Self-Injurious Behavior, and Severe Tantrums in Autism Spectrum Disorders: A Chart Review Study

    Science.gov (United States)

    Adler, Benjamin A.; Wink, Logan K.; Early, Maureen; Shaffer, Rebecca; Minshawi, Noha; McDougle, Christopher J.; Erickson, Craig A.

    2015-01-01

    Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define…

  19. Evaluation of patients on sertindole treatment after failure of other antipsychotics: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Hansen Karina

    2008-03-01

    Full Text Available Abstract Background Use of the atypical antipsychotic sertindole was suspended for four years due to safety concerns. During the suspension, the regulatory authorities required further studies, including this one, to be conducted. The purpose of this study was to determine if a subset of patients with psychotic illness exists which particularly benefits from sertindole treatment after failure of other antipsychotic drugs, including atypical antipsychotics. Methods This was a retrospective single-arm observational crossover study of 344 patients, who served as their own controls. Patients mainly from the Sertindole Safety Study who had shown good response to sertindole, and who had followed up to four alternating six month periods of treatment with sertindole and other antipsychotics, were included. (In Period 1 patients took non-sertindole treatment, in Period 2, sertindole was taken, in Period 3, patients reverted to non-sertindole treatment, and in Period 4, sertindole was taken again. Patient records for each period of treatment were assessed for objective data: number and duration of hospitalizations due to worsening of psychotic symptoms; the amount of self-harming behaviour; indicators of social status. Retrospective evaluation of changes in clinical symptoms from the patients' records was also conducted. Dates and reasons for stopping and/or switching medication were also recorded. Results There was improvement in all objective measured parameters during the periods of sertindole treatment. In particular, the average number of hospitalizations per year due to worsening of psychotic symptoms was reduced in the following way in the group studied over four treatment periods: Period 1 (non-sertindole treatment 3.4; Period 2 (sertindole treatment 1.0; Period 3 (non-sertindole treatment 2.0; Period 4 (sertindole treatment 1.8. The duration of hospitalizations also decreased significantly during the periods of sertindole treatment. Results

  20. Interaction between anti-Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice

    Directory of Open Access Journals (Sweden)

    Saki Shimizu

    2015-04-01

    Full Text Available Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD. Here, we examined the effects of cholinesterase inhibitors (ChEIs, donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3–3 mg/kg did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg in dose-dependent and synergistic manners. Galantamine (0.3–3 mg/kg elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist, but not by mecamylamine (a nicotinic antagonist. In addition, the bradykinesia potentiation by galantamine was significantly reduced by (±-8-hydroxy-2-(di-n-propylamino-tetralin (a 5-HT1A agonist, ritanserin (a 5-HT2 antagonist, and SB-258585 (a 5-HT6 antagonist. The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD.

  1. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  2. Short-term cognitive improvement in schizophrenics treated with typical and atypical neuroleptics.

    Science.gov (United States)

    Rollnik, Jens D; Borsutzky, Marthias; Huber, Thomas J; Mogk, Hannu; Seifert, Jürgen; Emrich, Hinderk M; Schneider, Udo

    2002-01-01

    Atypical neuroleptics seem to be more beneficial than typical ones with respect to long-term neuropsychological functioning. Thus, most studies focus on the long-term effects of neuroleptics. We were interested in whether atypical neuroleptic treatment is also superior to typical drugs over relatively short periods of time. We studied 20 schizophrenic patients [10 males, mean age 35.5 years, mean Brief Psychiatric Rating Scale (BPRS) score at entry 58.9] admitted to our hospital with acute psychotic exacerbation. Nine of them were treated with typical and 11 with atypical neuroleptics. In addition, 14 healthy drug-free subjects (6 males, mean age 31.2 years) were enrolled in the study and compared to the patients. As neuropsychological tools, a divided attention test, the Vienna reaction time test, the Benton visual retention test, digit span and a Multiple Choice Word Fluency Test (MWT-B) were used during the first week after admission, within the third week and before discharge (approximately 3 months). Patients scored significantly worse than healthy controls on nearly all tests (except Vienna reaction time). Clinical ratings [BPRS and Positive and Negative Symptom Scale for Schizophrenia (PANSS)] improved markedly (p divided attention task (r = 0.705, p = 0.034). Neuropsychological functioning (explicit memory, p divided attention, p < 0.05) moderately improved for both groups under treatment but without a significant difference between atypical and typical antipsychotic drugs. Over short periods of time (3 months), neuropsychological disturbances in schizophrenia seem to be moderately responsive to both typical and atypical neuroleptics. Copyright 2002 S. Karger AG, Basel

  3. Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

    Science.gov (United States)

    Miroshnichenko, Igor I; Baymeeva, Natalia V

    2018-04-07

    A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

  4. The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication

    NARCIS (Netherlands)

    da Silva Alves, Fabiana; Figee, Martijn; van Amelsvoort, Thérèse; Veltman, Dick; de Haan, Lieuwe

    2008-01-01

    The revised dopamine (DA) hypothesis states that clinical symptoms of schizophrenia are caused by an imbalance of the DA system. In this article, we aim to review evidence for this hypothesis by evaluating functional magnetic resonance imaging studies in schizophrenia. Because atypical drugs are

  5. Endocrine and Metabolic Adverse Effects of Psychotropic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Evrim Aktepe

    2011-12-01

    Full Text Available ABSTRACT Much as an increase in the use of psychotropic drugs is observed in children and adolescents over the last decade, the endocrine and metabolic side effects of these drugs can limit their use. Atypical antipsychotics can cause many side effects, which are not suitable for the developmental periods of children and adolescents, such as those related with thyroid, blood sugar, level of sex hormones, growth rate and bone metabolism. Children are under a more serious risk regarding the weight increasing effects of atypical antipsychotics and weight gain that is not proportionate with age is especially important due to the association between glucose or lipid abnormalities and cardiovascular mortality. Aripiprazole and ziprasidone are the least risky antipsychotic drugs when it comes to metabolic side affects. The antipsychotic drug that is associated with weight increase and diabetes in children and adolescents most is olanzapine. Even though there are no comparative long-term data concerning children, it is suggested by the currently available information that metabolic side effects including dyslipidemia and impaired glucose tolerance are at an alarming level when it comes to long-term treatment with antipsychotics. The most risky agents in terms of hyperglycemia and glucosuria development are olanzapine and clozapine. Use of risperidone and haloperidol should be undertaken with caution since it may bring about the risk of hyperprolactinemia. Among the antidepressants associated with weight loss and suppression of appetite are selective serotonin reuptake inhibitors, bupropion and venlafaxine. Thyroid functions can be affected by lithium, carbamazepine and valproate treatments. It is reported that the side effect most frequently associated with valproate is weight increase. The relationship between valproate treatment and the development of hyperandrogenism and polycystic ovary syndrome in young women should also be kept in mind. [TAF Prev

  6. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

    compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

  7. Influence of the drug exposure definition on the assessment of the antipsychotic metabolic impact in patients initially treated with mood-stabilizers.

    Science.gov (United States)

    Tournier, Marie; Bégaud, Bernard; Cougnard, Audrey; Auleley, Guy-Robert; Deligne, Jean; Blum-Boisgard, Claudine; Thiébaut, Anne C M; Verdoux, Hélène

    2012-07-01

    • Metabolic disturbances represent a well-known side effect of second generation antipsychotics. However, studies comparing second generation antipsychotic drugs (SGAPs) and first generation antipsychotic drugs (FGAPs) through administrative databases have shown contrasting findings, which may be attributable to methodological differences. • The definition of antipsychotic exposure impacts on the association between antipsychotics and metabolic risk in studies carried out through administrative databases. • Considering cumulative exposure to antipsychotics or including patients exposed to an antipsychotic drug for months or years is likely to over-represent patients who tolerate the drug well with a depletion of susceptible effects. • Antipsychotic drug exposure is a time-varying determinant and episodes of no use, past use and current use should be distinguished over the study period to avoid any misclassification bias that might lead to misleading findings. To assess the influence of three definitions of antipsychotic exposure on the comparison between first generation (FGAP) and second generation (SGAP) antipsychotic drugs and 'conventional' mood stabilizers towards the risk of metabolic events using (i) a dichotomous measure (exposed/non-exposed over the follow-up), (ii) a categorical measure taking into account the chronology of exposure at the time of the metabolic event (current, recent and no use) and (iii) a continuous measure (cumulative duration). A historical fixed cohort was identified from the 2004-2006 claims database of the French health insurance programme for self-employed workers, including 3172 patients aged 18 years and over who used conventional mood stabilizers over a 3 month period. A metabolic event was defined as an incident dispensing of an anti-diabetic or lipid-lowering drug. A metabolic event occurred in 367 patients (11.6%). At least one FGAP had been prescribed in 29% of patients who did not develop a metabolic event and in

  8. Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

    Science.gov (United States)

    Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

    2012-05-10

    Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity.

    Science.gov (United States)

    Tuplin, Erin W; Holahan, Matthew R

    2017-11-14

    The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating cognitive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes. To identify evidence in the literature that elucidates the pharmacological profile of aripiprazole.s. We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy, side-effects, pharmacology, and effects in animal models of schizophrenia symptoms. Aripiprazole is a newer atypical antipsychotic that displays a unique pharmacological profile, including partial D2 agonism and functionally selective properties. Aripiprazole is effective at treating the positive symptoms of schizophrenia and has the potential to treat negative and cognitive symptoms at least as well as other atypical antipsychotics. The drug has a favorable side-effect profile and has a low propensity to result in EPS or metabolic syndromes. Animal models of schizophrenia have been used to determine the efficacy of aripiprazole in symptom management. In these instances, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse inhibition, and social withdrawal. Because aripiprazole requires a greater than 90% occupancy rate at D2 receptors to be clinically active and does not produce EPS, this suggests a functionally selective effect on intracellular signaling pathways. A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms. This review

  10. Prediabetes in patients treated with antipsychotic drugs.

    Science.gov (United States)

    Manu, Peter; Correll, Christoph U; van Winkel, Ruud; Wampers, Martien; De Hert, Marc

    2012-04-01

    In 2010, the American Diabetes Association (ADA) proposed that individuals with fasting glucose level of 100-125 mg/dL (5.6-6.9 mmol/L) or glucose level of 140-199 mg/dL (7.8-11.0 mmol/L) 2 hours after a 75-g oral glucose tolerance test or hemoglobin A(1c) 5.7%-6.4% be classified as prediabetic, indicating increased risk for the emergence of diabetes mellitus. At the same time, the ADA formulated guidelines for the use of metformin for the treatment of prediabetes. To determine the prevalence of prediabetes in a cohort of psychiatrically ill adults receiving antipsychotics and to compare the clinical and metabolic features of prediabetic patients with those of patients with normal glucose tolerance and those with diabetes mellitus. The 2010 ADA criteria were applied to a large, consecutive, single-site European cohort of 783 adult psychiatric inpatients (mean age: 37.6 years) without a history of diabetes who were receiving antipsychotics. All patients in this cross-sectional study underwent measurement of body mass index (BMI), waist circumference, oral glucose tolerance test, and fasting insulin and lipids from November 2003 through July 2007. 413 patients (52.8%) had normal glucose tolerance, 290 (37.0%) had prediabetes, and 80 (10.2%) had diabetes mellitus. The fasting glucose and/or hemoglobin A(1c) criteria were met by 89.7% of prediabetic patients. A statistically significant intergroup gradient from normal glucose tolerance to prediabetes and from prediabetes to diabetes mellitus was observed for waist circumference, triglycerides, fasting insulin levels, and frequency of metabolic syndrome (P = .02 to P prediabetic patients (6.6%) met the 2010 ADA criteria for treatment with metformin. Prediabetes is highly prevalent in adults treated with antipsychotic drugs and correlates with markers of increased intraabdominal adiposity, enhanced lipolysis, and insulin resistance. Criteria for using metformin to prevent the emergence of diabetes mellitus may need to be

  11. Prevalence and correlates of atypical patterns of drug use progression: findings from the South African Stress and Health Study

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    Myers, B; van Heerden, MS; Grimsrud, A; Myer, L; Williams, DR; Stein, DJ

    2012-01-01

    Objective Atypical sequences of drug use progression are thought to have important implications for the development of substance dependence. The extent to which this assumption holds for South African populations is unknown. This paper attempts to address this gap by examining the prevalence and correlates of atypical patterns of drug progression among South Africans. Method Data on substance use and other mental health disorders from a nationally representative sample of 4351 South Africans were analysed. Weighted cross tabulations were used to estimate prevalence and correlates of atypical patterns of drug use progression. Results Overall, 12.2% of the sample reported atypical patterns of drug use progression. The most common violation was the use of extra-medical drugs prior to alcohol and tobacco. Gender was significantly associated with atypical patterns of drug use with the risk pattern varying by the type of drug. None of the anxiety or mood disorders were associated with atypical patterns of use. Atypical patterns of drug use were not associated with increased risk for a lifetime substance use disorder. Conclusion Atypical patterns of drug use initiation seem more prevalent in South Africa compared to other countries. The early use of extra-medical drugs is common, especially among young women. Drug availability and social environmental factors may influence patterns of drug use. The findings have important implications for prevention initiatives and future research. PMID:21509404

  12. Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review.

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    Luijendijk, Hendrika J; de Bruin, Niels C; Hulshof, Tessa A; Koolman, Xander

    2016-02-01

    Numerous large observational studies have shown an increased risk of mortality in elderly users of conventional antipsychotics. Health authorities have warned against use of these drugs. However, terminal illness is a potentially strong confounder of the observational findings. So, the objective of this study was to systematically assess whether terminal illness may have biased the observational association between conventional antipsychotics and risk of mortality in elderly patients. Studies were searched in PubMed, CINAHL, Embase, the references of selected studies and articles referring to selected studies (Web of Science). Inclusion criteria were (i) observational studies that estimated (ii) the risk of all-cause mortality in (iii) new elderly users of (iv) conventional antipsychotics compared with atypical antipsychotics or no use. Two investigators assessed the characteristics of the exposure and reference groups, main results, measured confounders and methods used to adjust for unmeasured confounders. We identified 21 studies. All studies were based on administrative medical and pharmaceutical databases. Sicker and older patients received conventional antipsychotics more often than new antipsychotics. The risk of dying was especially high in the first month of use, and when haloperidol was administered per injection or in high doses. Terminal illness was not measured in any study. Instrumental variables that were used were also confounded by terminal illness. We conclude that terminal illness has not been adjusted for in observational studies that reported an increased risk of mortality risk in elderly users of conventional antipsychotics. As the validity of the evidence is questionable, so is the warning based on it. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Occupancy of dopamine D-2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia

    NARCIS (Netherlands)

    de Haan, Lieuwe; Booij, Jan; Lavalaye, Jules; van Amelsvoort, Therese; Linszen, Don

    2006-01-01

    Rationale: Occupancy of dopamine D-2 receptors by antipsychotic drugs depends on the individual availability of D-2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior.

  14. Antipsychotics and Sexual Dysfunction: Sexual Dysfunction - Part III

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    Anil Kumar Mysore Nagaraj

    2009-11-01

    Full Text Available Satisfying sexual experience is an essential part of a healthy and enjoyable life for most people. Antipsychotic drugs are among the various factors that affect optimal sexual functioning. Both conventional and novel antipsychotics are associated with significant sexual side effects. This review has presented various studies comparing different antipsychotic drugs. Dopamine antagonism, increased serum prolactin, serotonergic, adrenergic and cholinergic mechanisms are all proposed to be the mechanisms for sexual dysfunction. Drug treatment for this has not given satisfactory long-term results. Knowledge of the receptor pharmacology of an individual antipsychotic will help to determine whether it is more or less likely to cause sexual side effects and its management.

  15. Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns

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    de la Fuente-Sandoval Camilo

    2004-04-01

    Full Text Available Abstract Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs. These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS, risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some

  16. A review of the evidence for the use of metformin in the treatment of metabolic syndrome caused by antipsychotics.

    Science.gov (United States)

    Jesus, Cátia; Jesus, Inês; Agius, Mark

    2015-09-01

    Psychiatric patients requiring therapy with antipsychotics have a greater incidence of becoming overweight or obese compared with the general population. Many of these patients are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidaemia, and other metabolic derangements. The most important and first line of treatment for the metabolic syndrome is lifestyle changes including diet and exercise. However, other approaches like the use of medication (e.g. Metformin) have been also used, mainly when the lifestyle changes are difficult to achieve. Therefore, the treatment of antipsychotic-induced weight gain with metformin may be an option after the lifestyle and dietary changes fail. The use of metformin is still experimental and off license regarding the treatment of metabolic syndrome in Psychiatric patients, however we wished to assess the evidence for its use. Our study is a literature based research. For our research we reviewed 12 Pubmed published articles from 2006 to 2013. Metformin have been reported to counteract effectively antipsychotic-induced body weight gain and has been demonstrated to improve glycaemic control and promote a moderate weight loss in both diabetic and non-diabetic subjects. Metformin use appears to be a benefit when started early in the course of treatment and mostly in young adults newly exposed to antipsychotic drugs.

  17. Impulsivity and novel object recognition test of rat model for vascular cognitive impairment after antipsychotics treatment

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    Ronny T Wirasto

    2016-12-01

    Full Text Available ABSTRACT Vascular cognitive impairment (VCI is a common condition in which no standard treatment has been approved. VCI is often accompanied by behavioral problems which require psychiatric interventions. The common therapeutic agent used for the acute management is antipsychotic injections. Current findings showed that atypical antipsychotic possess better safety profile for treating behavioral problems related to VCI compared to typical antipsychotic. In this study, we induced VCI in Sprague Dawley rats between 6-8 weeks old using bilateral carotid communist artery occlusion technique. The subjects were divided into 4 treatment groups: sham, olanzapine, haloperidol, and risperidone groups. Subjects received intramuscular injections of subsequent drugs for 3 days post VCI induction. Impulsive behavior and object recognition were examined using cliff jumping test and novel object recognition test. The analyses results showed that impulsive behavior was lower in the olanzapine and haloperidol groups compared to sham group, although it was not statistically significant (p = 0.651. The results also showed that there were no significant differences in the time spent exploring old and novel objects in all groups (p = 0.945;0.637 respectively. In conclusion, antipsychotic injection might not be effective to control impulsive behavior post VCI induction.

  18. Perceptions on efficacy and side effects of conventional depot antipsychotics (CDA) and atypical depot antipsychotics (ADA): Psychiatrists versus patients in Hong Kong.

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    Tsang, Hector W H; Fong, Mandy W M; Fung, Kelvin M T; Chung, Raymond C K

    2010-03-01

    Abstract Objectives. We compared the satisfaction level of psychiatrists and psychiatric patients towards conventional (CDA) and atypical (ADA) depot antipsychotics on symptom management, role functioning, and side effects. Method. Patients from an out-patient clinic of a public hospital and psychiatrists from public hospitals participated in the survey in 2007-2008. A total of 153 patients were interviewed by a tailor-made questionnaire and 72 psychiatrists self-administered a similar questionnaire. Results. Both groups shared similar attitudes towards clinical effectiveness and treatment efficacy of ADA and CDA. More patients were ambivalent towards relapse prevention of CDA than psychiatrists (30.7 vs. 16.7%, PADA are associated with less side effects. More than half of the patients showed negative attitudes towards the effectiveness of CDA on improving quality of life (52.40%), work (57.50%), and recreation (55.50%). Psychiatrists were more aware of the limitation of CDA and severity of side effects of CDA. They did not, however, seem to incorporate patients' opinions and research findings into their clinical practice. Conclusion. Evidence-based practice and shared decision-making model between clinicians and mental patients should be advocated. More investigations should be devoted to examine the efficacy of ADA as the alternative to CDA.

  19. Antipsychotic-induced somnolence in mothers with schizophrenia.

    Science.gov (United States)

    Seeman, Mary V

    2012-03-01

    Although it is known that many antipsychotic drugs, at the doses prescribed for schizophrenia, are sedative and cause daytime drowsiness, the effect of potentially diminished vigilance on parenting parameters has not been studied. The aim of this paper is to advise clinicians about sedative load in mothers who are prescribed antipsychotic medication. A Medline search was conducted into the sedative effects of antipsychotics, with the following search terms: sleep; sedation; somnolence; wakefulness; antipsychotics; schizophrenia, parenting, maternal behavior, and custody. The results showed that antipsychotic drugs differ in their propensity to induce sedation and do so via their effects on a variety of neurotransmitter systems. It is important to note that mothers with schizophrenia risk losing custody of their infants if they are perceived as potentially neglectful because of excessive daytime sleepiness. Clinicians must choose antipsychotic medications carefully and monitor for sedative effects whenever the patient has important responsibilities that require the maintenance of vigilance.

  20. Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

    Science.gov (United States)

    Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

    2006-01-01

    Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (prelationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

  1. Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.

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    Newman-Tancredi, A; Gavaudan, S; Conte, C; Chaput, C; Touzard, M; Verrièle, L; Audinot, V; Millan, M J

    1998-08-21

    Recombinant human (h) 5-HT1A receptor-mediated G-protein activation was characterised in membranes of transfected Chinese hamster ovary (CHO) cells by use of guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS binding). The potency and efficacy of 21 5-HT receptor agonists and antagonists was determined. The agonists, 5-CT (carboxamidotryptamine) and flesinoxan displayed high affinity (subnanomolar Ki values) and high efficacy (Emax > 90%, relative to 5-HT = 100%). In contrast, ipsapirone, zalospirone and buspirone displayed partial agonist activity. EC50s for agonist stimulation of [35S]GTPgammaS binding correlated well with Ki values from competition binding (r = +0.99). Among the compounds tested for antagonist activity, methiothepin and (+)butaclamol exhibited 'inverse agonist' behaviour, inhibiting basal [35S]GTPgammaS binding. The actions of 17 antipsychotic agents were investigated. Clozapine and several putatively 'atypical' antipsychotic agents, including ziprasidone, quetiapine and tiospirone, exhibited partial agonist activity and marked affinity at h5-HT1A receptors, similar to their affinity at hD2 dopamine receptors. In contrast, risperidone and sertindole displayed low affinity at h5-HT1A receptors and behaved as 'neutral' antagonists, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Likewise the 'typical' neuroleptics, haloperidol, pimozide, raclopride and chlorpromazine exhibited relatively low affinity and 'neutral' antagonist activity at h5-HT1A receptors with Ki values which correlated with their respective Kb values. The present data show that (i) [35S]GTPgammaS binding is an effective method to evaluate the efficacy and potency of agonists and antagonists at recombinant human 5-HT1A receptors. (ii) Like clozapine, several putatively 'atypical' antipsychotic drugs display balanced serotonin h5-HT1A/dopamine hD2 receptor affinity and partial agonist activity at h5-HT1A receptors. (iii) Several 'typical' and some putatively 'atypical

  2. Characterization of Schizophrenia Adverse Drug Interactions through a Network Approach and Drug Classification

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    Jingchun Sun

    2013-01-01

    Full Text Available Antipsychotic drugs are medications commonly for schizophrenia (SCZ treatment, which include two groups: typical and atypical. SCZ patients have multiple comorbidities, and the coadministration of drugs is quite common. This may result in adverse drug-drug interactions, which are events that occur when the effect of a drug is altered by the coadministration of another drug. Therefore, it is important to provide a comprehensive view of these interactions for further coadministration improvement. Here, we extracted SCZ drugs and their adverse drug interactions from the DrugBank and compiled a SCZ-specific adverse drug interaction network. This network included 28 SCZ drugs, 241 non-SCZs, and 991 interactions. By integrating the Anatomical Therapeutic Chemical (ATC classification with the network analysis, we characterized those interactions. Our results indicated that SCZ drugs tended to have more adverse drug interactions than other drugs. Furthermore, SCZ typical drugs had significant interactions with drugs of the “alimentary tract and metabolism” category while SCZ atypical drugs had significant interactions with drugs of the categories “nervous system” and “antiinfectives for systemic uses.” This study is the first to characterize the adverse drug interactions in the course of SCZ treatment and might provide useful information for the future SCZ treatment.

  3. Metabolic Signature of Antipsychotics Used in the Treatment of Autism

    Science.gov (United States)

    2015-10-01

    Atypical antipsychotics (AAP) are prescribed to patients with autism spectrum disorders with symptoms of aggression or agitation, stereotypic behavior...AAP directly Increase the size of rat adipocytes Subcutaneous adipose explants from Sprague Dawley male rats (N=8) were incubated in DMEM/F12 and 5

  4. Dissemination of Evidence-Based Antipsychotic Prescribing Guidelines to Nursing Homes: A Cluster Randomized Trial.

    Science.gov (United States)

    Tjia, Jennifer; Field, Terry; Mazor, Kathleen; Lemay, Celeste A; Kanaan, Abir O; Donovan, Jennifer L; Briesacher, Becky A; Peterson, Daniel; Pandolfi, Michelle; Spenard, Ann; Gurwitz, Jerry H

    2015-07-01

    To evaluate the effectiveness of efforts to translate and disseminate evidence-based guidelines about atypical antipsychotic use to nursing homes (NHs). Three-arm, cluster randomized trial. NHs. NHs in the state of Connecticut. Evidence-based guidelines for atypical antipsychotic prescribing were translated into a toolkit targeting NH stakeholders, and 42 NHs were recruited and randomized to one of three toolkit dissemination strategies: mailed toolkit delivery (minimal intensity); mailed toolkit delivery with quarterly audit and feedback reports about facility-level antipsychotic prescribing (moderate intensity); and in-person toolkit delivery with academic detailing, on-site behavioral management training, and quarterly audit and feedback reports (high intensity). Outcomes were evaluated using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. Toolkit awareness of 30% (7/23) of leadership of low-intensity NHs, 54% (19/35) of moderate-intensity NHs, and 82% (18/22) of high-intensity NHs reflected adoption and implementation of the intervention. Highest levels of use and knowledge among direct care staff were reported in high-intensity NHs. Antipsychotic prescribing levels declined during the study period, but there were no statistically significant differences between study arms or from secular trends. RE-AIM indicators suggest some success in disseminating the toolkit and differences in reach, adoption, and implementation according to dissemination strategy but no measurable effect on antipsychotic prescribing trends. Further dissemination to external stakeholders such as psychiatry consultants and hospitals may be needed to influence antipsychotic prescribing for NH residents. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  5. [Cost-effectiveness analysis of schizophrenic patient care settings: impact of an atypical antipsychotic under long-acting injection formulation].

    Science.gov (United States)

    Llorca, P M; Miadi-Fargier, H; Lançon, C; Jasso Mosqueda, G; Casadebaig, F; Philippe, A; Guillon, P; Mehnert, A; Omnès, L F; Chicoye, A; Durand-Zaleski, I

    2005-01-01

    Schizophrenia is a disease affecting the young adults and amounts to approximately 300,000 people in France. The French public psychiatric sector takes care of approximately 150,000 adults schizophrenics: 50% benefit from ambulatory care, 50% are in partial or full-time hospitalization care. Schizophrenia represents the first diagnosis that psychiatric sectors take in charge. The costs associated with schizophrenia, mainly hospital costs, are important and were estimated at 2% of the total medical costs in France. In the French social welfare system, the social costs (pensions, allowances, managements of custody or guardianship by social workers) are also to be taken into account: it amounts to a third of the global direct cost. Schizophrenia also generates indirect costs (losses of productivity and premature deaths) which would be at least equal, or even more important, than direct medical costs. The non-compliance to the antipsychotic treatment is a major problem with people suffering from schizophrenia. Indeed the lack of compliance to the treatment, estimated at 20 to 40%, is a major handicap for schizophrenic patient stabilization. The poor level of compliance is due to many various causes: adverse effects that are considered unbearable, medicine viewed as persecutory, negation of the disease, nostalgia for the productive phases of the disease, lack of social support, complexity of the prescription, relapse itself. Compliance is thus influenced by the patient's clinical features, local provision of health care and the specific nature of the drug (adverse effects, pharmaceutical formulation). The atypical antipsychotics present fewer extrapyramidal side effects and reduce the cognitive deficits associated with the disease, which results in improved compliance. Long-acting injectable antipsychotics allow a better therapeutic compliance and thus better efficacy of the treatment. Several studies have shown a significant improvement in compliance related to the

  6. Elderly Patients with Dementia-Related Symptoms of Severe Agitation and Aggression: Consensus Statement on Treatment Options, Clinical Trials Methodology, and Policy

    Science.gov (United States)

    Salzman, C; Jeste, D; Meyer, RE; Cohen-Mansfield, J; Cummings, J; Grossberg, G; Jarvik, L; Kraemer, H; Lebowitz, B; Maslow, K; Pollock, B; Raskind, M; Schultz, S; Wang, P; Zito, JM; Zubenko, GS

    2009-01-01

    Atypical antipsychotic drugs have been used off-label in clinical practice for treatment of serious dementia-associated agitation and aggression. Following reports of cerebrovascular adverse events associated with the use of atypical antipsychotic in elderly patients with dementia, the FDA issued black box warnings for several atypical antipsychotics, titled “Cerebrovascular Adverse Events, including Stroke, in Elderly Patients with Dementia.” Subsequently, the FDA initiated a meta-analysis of safety data from 17 registration trials across six antipsychotic drugs (five atypical antipsychotics and haloperidol). In 2005, the Agency issued a black box warning regarding increased risk of mortality associated with the use of atypical antipsychotic drugs in this patient population. Geriatric mental health experts participating in a 2006 consensus conference reviewed evidence on the safety and efficacy of antipsychotics, as well as nonpharmacologic approaches, in treating dementia-related symptoms of agitation and aggression. They concluded that, while problems in clinical trials design may have been one of the contributors to the failure to find a signal of drug efficacy, the findings related to drug safety should be taken seriously by clinicians in assessing the potential risks and benefits of treatment in a frail population, and in advising families about treatment. Information provided to patients and family members should be documented in the patient’s chart. Drugs should be used only when non-pharmacologic approaches have failed to adequately control behavioral disruption. Participants also agreed that that there is a need for an FDA-approved medication for the treatment of severe, persistent or recurrent dementia-related symptoms of agitation and aggression (even in the absence of psychosis), that are unresponsive to nonpharmacologic intervention. The authors have outlined methodological enhancements to better evaluate treatment approaches in future

  7. Some novelties and recommendations by swithing antipsychotics

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    Nika Aleksandra Kravos

    2014-11-01

    Full Text Available Clinical outcome of patients with severe mental disorders treated with antipsychotics depends on individual response to therapy, adverse events, physical health, maintaining of physical health and of the patient’s, interpersonal (patient - therapist, health and environmental features. Replacement of antipsychotics is a common therapeutic measure. The response depends on mostly unknown genetic factors, physiological particularities of the patient and its variations. This article summarizes the most important and the most recent pharmacological properties and consequences of cross-action of antipsychotics. It specifies the basic rules and ways of replacing antipsychotic drugs in different clinical situations, and summarizes alerts, recommendations and suggestions when changing antipsychotics.

  8. Antipsychotic medications and stroke in schizophrenia: A case-crossover study.

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    Wen-Yin Chen

    Full Text Available The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia.Using a retrospective cohort of patients with schizophrenia (N = 31,976 derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010. We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug.Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009 within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037, and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015.Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

  9. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs

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    Nordon C

    2017-12-01

    Full Text Available Clementine Nordon,1 Constance Battin,1 Helene Verdoux,2 Josef Maria Haro,3 Mark Belger,4 Lucien Abenhaim,1 Tjeerd Pieter van Staa5 On behalf of the IMI GetReal WP2 Group 1Epidemiological Research, Analytica LASER, Paris, 2Population Health Research Center, Team Pharmaco-Epidemiology, UMR 1219, Bordeaux-2 University, INSERM, Bordeaux, France; 3Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 4Eli Lilly and Company Limited, Erl Wood Manor, Windlesham, 5Farr Institute, University of Manchester, Manchester, UK Purpose: A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level.Patients and methods: Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist’s gender, age, length of practice experience, practice setting and type, countries’ Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1 to estimate antipsychotic drugs’ effectiveness (defined as the association between patients’ outcome at 3 months – dependent variable, continuous – and antipsychotic drug initiation at baseline – drug A vs other antipsychotic drug; 2 to estimate the similarity between clustered data (using the intra-cluster correlation coefficient; and 3 to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term.Results: About 23% of the variance found for patients’ outcome was explained by unmeasured confounding at a center level. Psychiatrists’ practice experience was found to be associated with patient outcomes (p=0.04 and modified the relative effect of “drug A” (p<0.001, independent of center- or patient

  10. SEXUAL DYSFUNCTION INDUCED BY ANTI-PSYCHOTICS AND ANTI-DEPRESSANTS IN DRUG NAIVE PATIENTS – A COMPARATIVE STUDY

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    M. Mohanalakshmi

    2017-03-01

    Full Text Available BACKGROUND The aim of this study was to determine and compare sexual dysfunction caused by anti-psychotics and anti-depressants in drug naïve patients. MATERIALS AND METHODS Patients diagnosed as drug naïve schizophrenic and depression as per DSM-5 criteria & age between 18-45 years were recruited and allocated into group A (n=30–receiving anti-psychotics & group B (n=30 receiving anti-depressants after informed consent by the patients. Sexual dysfunction was assessed by Arizona Sexual Experiences Scale (ASEX during the initial 2 months of therapy. RESULTS ASEX mean for patients receiving antipsychotics increased from the baseline of 7.97 to 17.23 and the ASEX mean for patients receiving antidepressants increased from baseline of 7.80 to 18.67 with p value of 0.249 which is not statistically significant. Among the antipsychotics haloperidol ASEX mean increased from 7.87 to 18.00 and risperidone mean increased from 8.07 to 16.47 with the p value of 0.335 which is not significant. More patients on haloperidol showed evidence of sexual dysfunction as assessed by ASEX scoring than risperidone though p value was not significant. Among the two antidepressants ASEX score mean for amitriptyline patients increased from 8.07 to 16.47, and that of fluoxetine from 7.53 to 16.47 with the p value of 0.018* statistically significant at α of 0.05 level. CONCLUSION This study shows presence of sexual dysfunction in patients receiving antipsychotics & antidepressants by 2 nd month of therapy though statistically not significant. Fluoxetine group patients developed statistically significant sexual dysfunction. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account because this side effect adds to the emotional stress and worsening of mental dysfunction.

  11. Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features

    OpenAIRE

    Rabinowitz, Jonathan; Levine, Stephen Z.; Barkai, Orna; Davidov, Ori

    2008-01-01

    Dropout is often used as an outcome measure in clinical trials of antipsychotic medication. Previous research is inconclusive regarding (a) differences in dropout rates between first- and second-generation antipsychotic medications and (b) how trial design features reduce dropout. Meta-analysis of randomized controlled trials (RCTs) of antipsychotic medication was conducted to compare dropout rates for first- and second-generation antipsychotic drugs and to examine how a broad range of design...

  12. An epidemiological study of concomitant use of Chinese medicine and antipsychotics in schizophrenic patients: implication for herb-drug interaction.

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    Zhang-Jin Zhang

    Full Text Available BACKGROUND: Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. METHODS AND FINDINGS: In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI 34.2%-38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80-4.24. However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06-4.83. Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. CONCLUSIONS: Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.

  13. The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, M B; Fuxe, K; Werge, T

    2002-01-01

    The adenosine A2A receptor agonist CGS 21680 has shown effects similar to dopamine antagonists in behavioural assays in rats predictive for antipsychotic activity, without induction of extrapyramidal side-effects (EPS). In the present study, we examined whether this functional dopamine antagonism...... showed a functional anti-dopaminergic effect in Cebus apella monkeys without production of EPS. This further substantiates that adenosine A2A receptor agonists may have potential as antipsychotics with atypical profiles....

  14. Study on effects of an atypical antipsychotic, risperidone on regional cerebral blood flow with 99mTc-HMPAO SPECT in drug-naive and unmedicated schizophrenic patients

    International Nuclear Information System (INIS)

    Koiwa, Daisuke

    2003-01-01

    To examine the underlying mechanisms of intracerebral or clinical actions of the atypical antipsychotic, risperidone (RIS), the effects of RIS on absolute regional cerebral blood flows (rCBFs) measured with 99mTc-HMPAO SPECT and correlations between the rCBFs and psychotic symptoms assessed with positive and negative syndrome scale (PANSS) were investigated in 10 drug-naive and unmedicated schizophrenic patients with acute hallucinatory and delusional state. Both the SPECT and PANSS were repeated before and after oral 2-week administration of RIS 3 mg/day in all of the 10 patients and after subsequent 2-week administration of RIS 4-6 mg/day in half of the patients. The rCBF values were significantly decreased in the left precentral gyrus alone after the low dose of RIS 3 mg/day in comparison with before the RIS dose. The rCBF values were significantly decreased in the right cingulate, postcentral, inferior parietal gyri and the left inferior temporal gyrus after the high dose of RIS 4-6 mg/day in comparison with before the low dose of RIS 3 mg/day. The psychiatric assessment with PANSS showed an improvement of positive and negative symptoms after the low RIS dose and still more after the high RIS dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the low RIS dose showed a positive correlation between the rCBF values in the right middle temporal gyrus and hallucinations (mainly auditory hallucination). These results suggest that chronic RIS administration dose-dependently produces a decrease of rCBF in the cerebral cortex in the manner that the low dose decreases rCBF in a few restricted cortical regions, while the high dose induces the rCBF reduction in more widespread cortical regions. The RIS-induced rCBF decrease in the cerebral cortex is considered to be attributable to a secondary inactivation in the cerebral cortex due to D 2 dopamine receptor blockade of RIS in the striatum through the cortico

  15. Antipsychotics and physical attractiveness.

    Science.gov (United States)

    Seeman, Mary V

    2011-10-01

    Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

  16. Low dosage of aripiprazole induced neuroleptic malignant syndrome after interaction with other neuroleptic drugs

    Directory of Open Access Journals (Sweden)

    Albino Petrone

    2013-09-01

    Full Text Available Aripiprazole is a 2nd generation antipsychotic medication, atypical neuroleptic used for treatment of schizophrenia improving symptoms such as hallucinations, delusions, and disorganized thinking. A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS has been reported in association with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. The disease is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. We report on a 63-year old woman with depression syndrome who developed neuroleptic malignant syndrome after twelve days of aripripazole 5 mg per day. Our case is added to the small number already described and suggests the need for caution when aripripazole is added to increase the effect of other antipsychotics.

  17. Metabolic Signature of Antipsychotics used in the Treatment of Autism

    Science.gov (United States)

    2016-12-01

    pediatric, adult, and geriatric patients with schizophrenia, bipolar disorder, major depression, post-traumatic stress disorder and autism [1, 2]. While most...Endocrine manifestations of eating disorders. J.Clin.Endocrinol.Metab 96, 333-343 60. Jin,H. et al. (2008) Impact of atypical antipsychotic therapy on...2010) Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis

  18. Side effects as influencers of treatment outcome.

    Science.gov (United States)

    Sharif, Zafar

    2008-01-01

    Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.

  19. Antipsychotic-associated psoriatic rash - a case report

    DEFF Research Database (Denmark)

    Bujor, Camelia-Eugenia; Vang, Torkel; Nielsen, Jimmi

    2017-01-01

    BACKGROUND: Antipsychotics are a heterogeneous group of drugs. Although, antipsychotics have been used for years, unexpected side effects may still occur. With this case report we focus on a possible association between psoriasis and antipsychotics. Data on the patient's course of psychiatric...... disease, onset of psoriasis and its evolution were extracted from the patient's medical files. CASE PRESENTATION: We present a case of a 21-year-old female diagnosed with schizophrenia. She was initially treated with quetiapine, and later switched to aripiprazole due to weight gain. After initiation...

  20. Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

    Science.gov (United States)

    Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

    2018-04-01

    Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

  1. Synthesis and pharmacological characterization of novel N-(trans-4-(2-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)cyclohexyl)amides as potential multireceptor atypical antipsychotics.

    Science.gov (United States)

    Chen, Xiao-Wen; Sun, Yuan-Yuan; Fu, Lei; Li, Jian-Qi

    2016-11-10

    A series of novel benzisothiazolylpiperazine derivatives combining potent dopamine D2 and D3, and serotonin 5-HT1A and 5-HT2A receptor properties were synthesized and evaluated for their potential antipsychotic properties. The most-promising derivative was 9j. The unique pharmacological features of 9j were a high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors, together with a 20-fold selectivity for the D3 versus D2 subtype, and a low affinity for muscarinic M1 (reducing the risk of anticholinergic side effects), and for hERG channels (reducing incidence of QT interval prolongation). In animal behavioral models, 9j inhibited the locomotor-stimulating effects of phencyclidine, blocked conditioned avoidance response, and improved the cognitive deficit in the novel object recognition tests in rats. 9j exhibited a low potential for catalepsy, consistent with results with risperidone. In addition, favorable brain penetration of 9j in rats was detected. These studies have demonstrated that 9j is a potential atypical antipsychotic candidate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment.

    Science.gov (United States)

    Barr, Alasdair M; Procyshyn, Ric M; Hui, Philip; Johnson, Joy L; Honer, William G

    2008-03-01

    The prevalence of smoking in schizophrenia has reliably been reported as being higher than for any other psychiatric disorder. While a number of theories have been proposed to account for such high rates of smoking, little is known about the subjective motivation for why schizophrenia patients smoke in comparison with those without the disease. The aim of the present study was to evaluate and compare smoking motivation in control subjects and schizophrenia patients, and determine if factors such as type of medication or access to cigarettes could contribute to self-reported motivation for smoking. We assessed motivation to smoke in 61 schizophrenia inpatients and 33 non-psychiatric health worker controls at a tertiary care psychiatric facility in a cross-sectional study. Nicotine dependency and smoking behavior were evaluated using the Fagerstrom Test for Nicotine Dependence and a validated questionnaire that assesses motivation for smoking along seven different dimensions. Schizophrenia patients reported a stronger motivation to smoke than controls for reasons related to pleasure from the act of smoking, as well as a need for psychomotor stimulation. Scores on both these factors were significantly associated with daily antipsychotic drug dose. The sedative and anxiolytic effects of smoking were related to anticholinergic load of psychiatric medications. The findings highlight important differences in self-reported motivation to smoke between schizophrenia patients and normals. Antipsychotic drugs may also influence aspects of motivation to smoke.

  3. An explorative study of school performance and antipsychotic medication

    NARCIS (Netherlands)

    van der Schans, J.; Vardar, S; Cicek, R.; Bos, H. J.; Hoekstra, P. J.; de Vries, T. W.; Hak, E.

    2016-01-01

    Background: Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. Methods:

  4. Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors.

    Science.gov (United States)

    Leucht, Stefan; Leucht, Claudia; Huhn, Maximilian; Chaimani, Anna; Mavridis, Dimitris; Helfer, Bartosz; Samara, Myrto; Rabaioli, Matteo; Bächer, Susanne; Cipriani, Andrea; Geddes, John R; Salanti, Georgia; Davis, John M

    2017-10-01

    Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression. The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time. Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

  5. Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics

    International Nuclear Information System (INIS)

    Dresel, S.; Tatsch, K.; Meisenzahl, E.; Scherer, J.

    2002-01-01

    Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [de

  6. Serum total homocystein, folate and vitamin B12 levels and their correlation with antipsychotic drug doses in adult male patients with chronic schizophrenia.

    Science.gov (United States)

    Eren, Esin; Yeğin, Ayşenur; Yilmaz, Necat; Herken, Hasan

    2010-01-01

    Elevated blood levels of homocysteine (hCY) have been associated with schizophrenic male patients. However, controversy remains regarding the association between lowered plasma folate and vitamin B12, hyperhomocysteinemia, and schizophrenia. Sixty-six (66) male patients with chronic schizophrenia were investigated to test the hypotheses that alterations in Hcy, folate, and vitamin B12 levels might be related to the antipsychotic drug doses used in treatment. Serum total homocysteine, folic acid, and vitamin B12 levels were determined by chemiluminescence methods in both patients and control subjects. The patients were grouped according to the antipsychotic drug doses used in their treatment. Patients had higher homocysteine levels but they did not differ from controls in terms of folate and vitamin B12 levels. On the other hand, only folate levels were negatively correlated in the patient group treated with higher therapeutic doses of chlorpromazine equivalents (> 400 mg/day) compared to the patient group with lower doses (< 400 mg/day). Our findings show that higher typical antipsychotic drugs may play a role as modifiying factor for folate metabolism in chronic schizoprenic male patients.

  7. Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1

    DEFF Research Database (Denmark)

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila

    2015-01-01

    have previously found that the atypical antipsychotics clozapine and olanzapine inhibited G protein activation and, surprisingly, induced both internalization and lysosomal degradation of 5-HT7 receptors. Here, we aimed to determine the mechanism of clozapine- and olanzapine-mediated degradation of 5......-HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine...... of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1....

  8. Does mental health staffing level affect antipsychotic prescribing? Analysis of Italian national statistics.

    Science.gov (United States)

    Starace, Fabrizio; Mungai, Francesco; Barbui, Corrado

    2018-01-01

    In mental healthcare, one area of major concern identified by health information systems is variability in antipsychotic prescribing. While most studies have investigated patient- and prescriber-related factors as possible reasons for such variability, no studies have investigated facility-level characteristics. The present study ascertained whether staffing level is associated with antipsychotic prescribing in community mental healthcare. A cross-sectional analysis of data extracted from the Italian national mental health information system was carried out. For each Italian region, it collects data on the availability and use of mental health facilities. The rate of individuals exposed to antipsychotic drugs was tested for evidence of association with the rate of mental health staff availability by means of univariate and multivariate analyses. In Italy there were on average nearly 60 mental health professionals per 100,000 inhabitants, with wide regional variations (range 21 to 100). The average rate of individuals prescribed antipsychotic drugs was 2.33%, with wide regional variations (1.04% to 4.01%). Univariate analysis showed that the rate of individuals prescribed antipsychotic drugs was inversely associated with the rate of mental health professionals available in Italian regions (Kendall's tau -0.438, p = 0.006), with lower rates of antipsychotic prescriptions in regions with higher rates of mental health professionals. After adjustment for possible confounders, the total availability of mental health professionals was still inversely associated with the rate of individuals exposed to antipsychotic drugs. The evidence that staffing level was inversely associated with antipsychotic prescribing indicates that any actions aimed at decreasing variability in antipsychotic prescribing need to take into account aspects related to the organization of the mental health system.

  9. Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Zachary Freyberg

    2017-07-01

    Full Text Available For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

  10. Antipsychotic Prescriptions for Children Aged 5 Years or Younger

    Directory of Open Access Journals (Sweden)

    Ana Lòpez-De Fede

    2014-10-01

    Full Text Available The use of antipsychotics in very young children is of concern given the lack of empirical evidence in their efficacy and long-term impact on children’s health. This study examined the prescription of antipsychotics among children aged ≤5 years enrolled in a state Medicaid program. Secondary data analysis was conducted using the Medicaid administrative data of a southeastern state. Using SAS 9.3, descriptive statistics were performed to examine socio-demographic characteristics, psychiatric diagnoses, off-label use, receipt of medications from multiple psychotropic drug classes, and receipt of non-pharmacologic psychiatric services among children aged ≤5 years who received antipsychotic prescriptions in calendar year (CY 2011. A total of 112 children in the target age group received antipsychotics in CY 2011, the most common prescription being risperidone. The most common listed psychiatric diagnosis was attention deficit hyperactivity disorder. Two in five children received antipsychotics for off-label use. Three in four children also received medications from at least one other psychotropic drug class. More than half did not receive adjunct psychiatric services. State-level policies offering specific guidance and recommendations for antipsychotic use among very young children are urgently needed. Future research is warranted to examine long-term impact of such practices on children’s growth and development.

  11. Drug–drug conditioning between citalopram and haloperidol or olanzapine in a conditioned avoidance response model: implications for polypharmacy in schizophrenia

    Science.gov (United States)

    Sparkman, Nathan L.; Li, Ming

    2016-01-01

    Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. Following acquisition of the avoidance response, rats were then randomly assigned to receive vehicle, citalopram (10.0 mg/kg, intraperitoneally), haloperidol (0.05 mg/kg, subcutaneously), olanzapine (1.0 mg/kg, subcutaneously), combined haloperidol with citalopram, or combined olanzapine with citalopram treatment for seven avoidance test sessions. In comparison with antipsychotic treatment alone, combined treatment with citalopram potentiated the antiavoidance effect of olanzapine or haloperidol (to a lesser extent) during the seven drug-test sessions. In addition, repeated pairing of citalopram with haloperidol or olanzapine caused citalopram to show a newly acquired avoidance-disruptive effect. This effect was context specific because citalopram paired with haloperidol or olanzapine outside the avoidance testing context (i.e. home cages) did not show such an effect. These findings indicate that concurrent antidepressant and antipsychotic treatments may engender a DDC process that follows the general Pavlovian associative conditioning principles. They also indicate that adjunctive citalopram treatment may enhance the antipsychotic efficacy of haloperidol and olanzapine in the

  12. Comparison of the effectiveness of brand-name and generic antipsychotic drugs for treating patients with schizophrenia in Taiwan.

    Science.gov (United States)

    Hsu, Chih-Wei; Lee, Sheng-Yu; Wang, Liang-Jen

    2018-03-01

    The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Schizophrenia as a disconnection syndrome. Studies with functional magnetic resonance imaging and structural equation modeling

    International Nuclear Information System (INIS)

    Schloesser, R.; Wagner, G.; Koehler, S.; Sauer, H.

    2005-01-01

    Aside from characteristic psychopathological symptoms, cognitive deficits are a core feature of schizophrenia. These deficits can only be addressed within the context of widespread functional interactions among different brain areas. To examine these interactions, structural equation modeling (SEM) was used for the analysis of fMRI datasets. In a series of studies, both in antipsychotic-treated and drug-free schizophrenic patients, a pattern of enhanced thalamocortical functional connectivity could be observed as an indicator for possible disruptions of frontostriatal thalamocortical circuitry. Moreover, drug-free patients and those receiving typical antipsychotic drugs were characterized by reduced interhemispheric corticocortical connectivity. This difference relative to normal controls was less in patients under atypical antipsychotic drugs. The results could be interpreted as a beneficial effect of atypical antipsychotic drugs on information processing in schizophrenic patients. The present findings are consistent with the model of schizophrenia as a disconnection syndrome and earlier concepts of ''cognitive dysmetria'' in schizophrenia. (orig.) [de

  14. Polymorphisms of the LEP- and LEPR Gene and Obesity in Patients Using Antipsychotic Medication

    NARCIS (Netherlands)

    Gregoor, Jochem G.; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J. G. M.; Egberts, Antoine C. G.; Heerdink, Eibert R.

    Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/ A polymorphism are associated with

  15. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

    Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

  16. Association between the HTR2C rs1414334 C/G gene polymorphism and the development of the metabolic syndrome in patients treated with atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    José María Rico-Gomis

    2016-07-01

    Full Text Available Few studies have assessed the association between the rs1414334 C/G polymorphism in the HTR2C gene and the development of the metabolic syndrome in patients treated with atypical antipsychotics. To provide further evidence, a cross-sectional study was conducted in Spain between 2012 and 2013 in 166 patients with these characteristics. In these patients, the association between the polymorphism and the presence of the metabolic syndrome was determined by implementing binary logistic regression models adjusted for variables associated with the metabolic syndrome. We did not confirm previous claims that the C allele of the polymorphism was linked to the metabolic syndrome: the association was in the opposite direction and non-significant. This conclusion held after taking gender and lifestyle variables into account.

  17. The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

    Science.gov (United States)

    Achilla, Evanthia; McCrone, Paul

    2013-04-01

    -acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results. Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions. Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.

  18. [The key role of patient in the antipsychotic therapy: shared decision making, adherence and research].

    Science.gov (United States)

    Gallingani, Francesca; Piccinni, Carlo; Simeoni, Angela; Poluzzi, Elisabetta; Menchetti, Marco; Berardi, Domenico

    2015-11-01

    A large number of currently available antipsychotic drugs are included into two main classes: traditional (or first-generation), and atypical (or second-generation) antipsychotics. This wide availability of medicinal products allows, at least in part, to address the need to identify the most appropriate treatment for the individual patient. A precondition for the effectiveness of antipsychotic treatment is the adherence, a multi-determined phenomenon that depends on factors related to the pharmacological properties of each agent and on factors independent from the therapy: among them, therapeutic alliance between patients and medical team, patient's belief in benefits and risks of medicines, and patient's relationship with the family and social environment are the most clearly recognized. The collection of data from patient helps the management of the individual clinical case, but this information could also become a source of data for research. In both cases, data must be collected in a ordered and well-coded way, therefore numerous instruments (like questionnaires and registers) are developing. This approach permits to make a recognition of patient's perception of his health condition, as well as the positive and negative outcomes of his pharmacological treatment. These tools are known in the literature by the name of PROMs (patient-reported outcome measures). From the clinical point of view, the PROMs can reduce the gap between patient and clinician in different therapeutic areas. They also enables the physician to identify the most suitable treatment to the individual patient, to meet his needs and preferences, and to adapt the therapy over time to the changes of his medical condition. About the research, the effects reported by the patient, in terms of both benefits and adverse reactions, represent important information useful to conduct observational studies that better define the benefit-risk profile of drug therapies, especially in psychiatry.

  19. Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Jiezhong Chen

    2017-11-01

    Full Text Available Antipsychotic drugs (APDs are widely prescribed to control various mental disorders. As mental disorders are chronic diseases, these drugs are often used over a life-time. However, APDs can cause serious glucometabolic side-effects including type 2 diabetes and hyperglycaemic emergency, leading to medication non-compliance. At present, there is no effective approach to overcome these side-effects. Understanding the mechanisms for APD-induced diabetes should be helpful in prevention and treatment of these side-effects of APDs and thus improve the clinical outcomes of APDs. In this review, the potential mechanisms for APD-induced diabetes are summarized so that novel approaches can be considered to relieve APD-induced diabetes. APD-induced diabetes could be mediated by multiple mechanisms: (1 APDs can inhibit the insulin signaling pathway in the target cells such as muscle cells, hepatocytes and adipocytes to cause insulin resistance; (2 APD-induced obesity can result in high levels of free fatty acids (FFA and inflammation, which can also cause insulin resistance. (3 APDs can cause direct damage to β-cells, leading to dysfunction and apoptosis of β-cells. A recent theory considers that both β-cell damage and insulin resistance are necessary factors for the development of diabetes. In high-fat diet-induced diabetes, the compensatory ability of β-cells is gradually damaged, while APDs cause direct β-cell damage, accounting for the severe form of APD-induced diabetes. Based on these mechanisms, effective prevention of APD-induced diabetes may need an integrated approach to combat various effects of APDs on multiple pathways.

  20. [Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

    Science.gov (United States)

    Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

    2014-01-01

    drug with more risk of abandoning due to adverse effects, followed by clozapine. Amisulpride, haloperidol and ziprasidone had favourable results as regards weight increase in several comparisons. Aripiprazole and paliperidone obtained a higher number of favourable results as regards sedation, and all the atypical drugs (except paliperidone) had a lower risk than the use of anti-parkinsonian drugs. Of the evidence from observational studies, it was found that, in subjects with risk factors for diabetes, such as age, hypertension, and dyslipidaemia, the initial treatment and current treatment with olanzapine, as well as current treatment with clozapine, may promote the development of this disease. Although it is imperative to prescribe an antipsychotic for treatment of the acute phase, the selection of the drug depends on the particular clinical condition of each patient and their collateral effects profile. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  1. sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H]SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes

    International Nuclear Information System (INIS)

    Tam, S.W.; Cook, L.

    1984-01-01

    The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[ 3 H]SKF 10,047 (N-allylnormetazocine) and to dopamine D 2 sites was investigated. In guinea pig brain membranes, (+)-[ 3 H]SKF 10,047 bound to single class of sites with a K/sub d/ of 4 x 10 -8 M and a B/sub max/ of 333 fmol/mg of protein. This binding was different from μ, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[ 3 H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[ 3 H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[ 3 H]SKF 10,047 binding sites did not correlate with those for [ 3 H]spiperone (dopamine D 2 ) sites. [ 3 H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-[ 3 H]SKF 10,047. In the striatum, about half of the saturable [ 3 H]haloperidol binding was to [ 3 H]spiperone (D 2 ) sites and the other half was to sites similar to (+)-[ 3 H]SKF 10,047 binding sites. 15 references, 4 figures, 1 table

  2. Haloperidol versus second-generation antipsychotics in the long-term treatment of schizophrenia.

    Science.gov (United States)

    Buoli, Massimiliano; Kahn, René S; Serati, Marta; Altamura, A Carlo; Cahn, Wiepke

    2016-07-01

    The purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed-up for 36 months. Two hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance. Patients treated with haloperidol discontinued more than the other groups (Breslow: risperidone p haloperidol group than in the olanzapine group (p haloperidol group than with olanzapine (p haloperidol. In addition, atypical antipsychotics seem to be more protective against recurrences than haloperidol. However, these results should be cautiously interpreted in the light of potential confounder factors such as duration of illness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Survey of atypical antipsychotic prescribing by Canadian child psychiatrists and developmental pediatricians for patients aged under 18 years.

    Science.gov (United States)

    Doey, Tamison; Handelman, Kenneth; Seabrook, Jamie A; Steele, Margaret

    2007-06-01

    To describe self-reported patterns of prescribing atypical antipsychotics (ATAs) and monitoring practices of child psychiatrists and developmental pediatricians in Canada. We surveyed members of the Canadian Academy of Child and Adolescent Psychiatry and members of the Developmental Paediatrics Section of the Canadian Paediatric Society regarding the types and frequencies of ATAs they prescribed, the ages and diagnoses of patients for whom they prescribed these medications, and the types and frequencies of monitoring used. Ninety-four percent of the child psychiatrists (95% CI, 90% to 97%) and 89% of the developmental pediatricians (95% CI, 75% to 96%) prescribed ATAs, most commonly risperidone (69%). Diagnoses included psychotic, mood, anxiety, externalizing, and pervasive developmental disorders. Prescribing for symptoms such as aggression, low frustration tolerance, and affect dysregulation was also common. Twelve percent of all prescriptions were for children under age 9 years. Most clinicians monitored patients, but there were wide variations in the type and frequency of tests performed. Despite the lack of formal indications, ATAs were prescribed by this group of clinicians for many off-label indications in youth under age 18 years, including very young children. Neither evidence-based guidelines nor a consensus on monitoring exist for this age group.

  4. Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children

    Science.gov (United States)

    Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias

    2010-01-01

    Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…

  5. Comparison of Medicaid spending in schizoaffective patients treated with once monthly paliperidone palmitate or oral atypical antipsychotics.

    Science.gov (United States)

    Xiao, Yongling; Muser, Erik; Fu, Dong-Jing; Lafeuille, Marie-Hélène; Pilon, Dominic; Emond, Bruno; Wu, Allen; Duh, Mei Sheng; Lefebvre, Patrick

    2016-01-01

    Compared to oral atypical antipsychotics (OAAs), long-acting injectable antipsychotics require less frequent administration, and thus may improve adherence and reduce risk of relapse in schizoaffective disorder (SAD) patients. To evaluate the impact of once monthly paliperidone palmitate (PP) versus OAAs on healthcare resource utilization, Medicaid spending, and hospital readmission among SAD patients. Using FL, IA, KS, MS, MO, and NJ Medicaid data (January 2009-December 2013), adults with ≥2 SAD diagnoses initiated on PP or OAA (index date) were identified. Baseline characteristics and outcomes were assessed during the 12month pre- and post-index periods, respectively. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to reduce confounding and compare the estimated treatment effect for PP versus OAA. A total of 10,778 OAA-treated patients and 876 PP-treated patients were selected. Compared to OAAs, PP was associated with significantly lower medical costs (PSM: mean monthly cost difference [MMCD] = -$383, p < 0.001; IPTW: MMCD = -$403, p = 0.016), which offset the higher pharmacy costs associated with PP (PSM: MMCD = $270, p < 0.001; IPTW: MMCD = $350, p < 0.001) and resulted in similar total healthcare cost (PSM: MMCD = -$113, p = 0.414; IPTW: MMCD = -$53, p = 0.697) for PP versus OAA. Reduced risk of hospitalization (PSM: incidence rate ratio [IRR] = 0.85, p = 0.128; IPTW: IRR = 0.96, p = 0.004) and fewer hospitalization days (PSM: IRR = 0.74, p = 0.008; IPTW: IRR = 0.85, p < 0.001) were observed in PP versus OAA patients. Among hospitalized patients, PP was associated with a lower risk of 30 day hospital readmission compared to OAA (IPTW: odds ratio = 0.89, p = 0.041). Limitations The Medicaid data may not be representative of the nation or other states, and includes pre-rebate pharmacy costs (potentially over-estimated). Also

  6. A Non-Interventional Naturalistic Study of the Prescription Patterns of Antipsychotics in Patients with Schizophrenia from the Spanish Province of Tarragona.

    Directory of Open Access Journals (Sweden)

    Ana M Gaviria

    Full Text Available The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes.To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain.A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013.The most used antipsychotic was risperidone, identified in 463 (26.3% patients, followed by olanzapine in 249 (14.1%, paliperidone in 225 (12.7%, zuclopenthixol in 201 (11.4%, quetiapine in 141 (8%, aripiprazole in 100 (5.7%, and clozapine in 100 (5.7%. Almost 8 out of 10 patients (79.3% were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6% were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94-40.97, LAI (OR 9.99, 95% CI 6.45-15.45, psychiatric co-medications (OR 4.25, 95% CI 2.72-6.64, and paliperidone (OR 3.13, 95% CI 1.23-7.92 were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35-0.83 and older age (OR 0.98, 95% CI 0.97-0.99 were related to a low polypharmacy probability.Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy is associated with the use of quetiapine or

  7. New drugs of abuse.

    Science.gov (United States)

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth

    2015-02-01

    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.

  8. Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.

    Science.gov (United States)

    Ballard, Clive; Isaacson, Stuart; Mills, Roger; Williams, Hilde; Corbett, Anne; Coate, Bruce; Pahwa, Rajesh; Rascol, Olivier; Burn, David J

    2015-10-01

    To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Primary and secondary care medical centers in the United States, Canada, Europe, and India. A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1

  9. Blockade of MK-801-induced heat shock protein 72/73 in rat brain by antipsychotic and monoaminergic agents targeting D2, 5-HT1A, 5-HT2A and α1-adrenergic receptors.

    Science.gov (United States)

    Romón, Tamara; Planas, Anna M; Adell, Albert

    2014-02-01

    Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can produce positive and negative symptomatology as well as impairment of cognitive function that closely resemble those present in schizophrenia. In rats, these drugs induce a behavioral syndrome (characterized by hyperlocomotion and stereotypies), an enhanced glutamatergic transmission in the medial prefrontal cortex, and damage to retrosplenial cortical neurons in adult rats, which was measured as the induction of the stress protein 72/73 kDa heat shock protein (Hsp72/73). In the present work, we have examined the existence of possible differences among different antipsychotic drugs in their capacity to block immunolabeling of Hsp72/73 in the retrosplenial cortex of the rat induced by the potent NMDA receptor antagonist, MK- 801. In addition, the effects of selective monoaminergic agents were also studied to delineate the particular receptors responsible for the actions of antipsychotic drugs. Pretreatment with clozapine, chlorpromazine, olanzapine, ziprasidone--and to a lesser extent haloperidol-reduced the formation of Hsp72/73 protein in the rat retrosplenial cortex after the administration of MK-801. In addition, antagonism at dopamine D2 (raclopride), 5-HT2 (M100907) and α1- adrenoceptors (prazosin) as well as agonism at 5-HT1A receptors (BAY x 3702) also diminished the MK-801-induced number of cells labeled with Hsp72/73. Each of these effects may contribute to antipsychotic action. The results suggest that the efficacy of atypical antipsychotic drugs in the clinic may result from a combined effect on 5-HT2, 5-HT1A and α1-adrenergic receptors added to the classical dopamine D2 receptor antagonism.

  10. Antipsychotic agents: efficacy and safety in schizophrenia

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2012-11-01

    Full Text Available Arão Nogueira de Araújo,1 Eduardo Pondé de Sena,1,2 Irismar Reis de Oliveira,1,3 Mario F Juruena41Postgraduation Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, Brazil; 4Stress and Affective Disorders Program, Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, BrazilAbstract: Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA and third generation antipsychotics (TGA, other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.Keywords: antipsychotic agents, schizophrenia, pharmacology, safety

  11. Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST).

    Science.gov (United States)

    Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A

    2015-06-01

    Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  12. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

    Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

  13. Comparison of Psychotropic Drug Prescribing Quality between Zagreb, Croatia and Sarajevo, B&H.

    Science.gov (United States)

    Polić-Vižintin, Marina; Štimac, Danijela; Čatić, Tarik; Šostar, Zvonimir; Zelić, Ana; Živković, Krešimir; Draganić, Pero

    2014-12-01

    The purpose of this paper was to compare outpatient consumption and quality of psychotropic drug prescribing between Croatia and Bosnia & Herzegovina 2006-2010. Data on drug utilization from Zagreb Municipal Pharmacy and Sarajevo Public Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the WHO Anatomical-Therapeutic-Chemical methodology. Total utilization of psychopharmaceuticals increased in both cities; however, it was higher in Zagreb than in Sarajevo throughout the study period. The utilization of psycholeptics increased in Zagreb by 2.4% (from 74.5 to 76.3 DDD/TID) and in Sarajevo by 3.8% (from 62.4 to 64.8 DDD/TID). The utilization of anxiolytics decreased in Zagreb by 2.1% and in Sarajevo by even 18.7%. The utilization of antidepressants increased in both cities with predominance of SSRI over TCA utilization, greater in Sarajevo (96.6%) than in Zagreb (10.2%). The anxiolytic/antidepressant ratio decreased by 11.1% in Zagreb (from 2.87 to 2.55) and by 58.7% in Sarajevo (from 5.66 to 2.34). Outpatient utilization of antipsychotics increased significantly in Sarajevo, predominated by typical ones, whereas in Zagreb the utilization of antipsychotics was stable, predominated by atypical ones. In Croatia and Bosnia & Herzegovina, there was an obvious tendency to follow western trends in drug prescribing, as demonstrated by the increased use of antidepressants and reduced use of anxiolytics. Despite some improvement observed in the prescribing quality, high use of antipsychotics with dominance of typical antipsychotics in Sarajevo points to the need of prescribing guidelines for antipsychotics.

  14. Olanzapine-Induced Neuroleptic Malignant Syndrome

    Directory of Open Access Journals (Sweden)

    Seyedhamze Hosseini

    2017-05-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine. The patient was adherent to treatment. He had decreased level of consciousness, muscle rigidity, diaphoresis, fever, drooling, urinary incontinence, and high blood pressure. This patient illustrates that NMS can occur due to treatment with atypical antipsychotic drugs like olanzapine, particularly in the presence of risk factors. This phenomenon is often unrecognized, underdiagnosed, or not treated properly. Physicians should be aware that NMS with extrapyramidal syndrome could occur with olanzapine at steady state doses without recent dosage adjustments or titration. It is essential that adequate and safe dose of medication is chosen and the patient is monitored by the signs and symptoms of this lethal syndrome.

  15. [Compliance of long-acting atypical antipsychotics: from an image problem to a question of indication].

    Science.gov (United States)

    Naudin, J; Dassa, D; Cermolacce, M

    2009-09-01

    This paper focuses on the questions asked to practitioners regarding compliance to new long-acting atypical antipsychotics (LAAA): how does the comprehensive approach of patients' and carers' attitudes facing treatment challenge it? A review of recent literature shows that LAAA, are still suffering from an "image problem". We aim to describe these negative beliefs and suggest that LAAA indications be reconsidered. Following a comprehensive approach, we interpreted our review on the basis of anthropological criteria. We focused on value-based health and disease models that organize the attitude of patients and carers regarding the depot injection. Multiple negative beliefs attached to the pain, side-effects, and stigmas are well-known to impair adhesion to treatment. Carers understand disease as a lack of insight. Patients experience it as a threat for the Self and a loss of autonomy. The nurse-patient relationship involving injections is an important factor of compliance. When time is devoted by the carer to paying attention to the patient's experience, in order to perceive the patient as a participant, patients are more likely to adopt the injectable route themselves. By doing so, the patient considers the injection as a "protective net" a "lesser evil" by integrating it within his(her) biography. A comprehensive approach links the lack of insight to the patient's perception of stigma. Hope for recovery is related by the person him(her)self to his(her) own ability for autonomy. Persons with schizophrenia usually struggle for norms (agonomia). This trend has to be taken into account. LAAA are better indicated when patients are compliant. There is no indication when patients are "pure agonomics" and fight to deny both stigma and medication.

  16. GABA concentration in schizophrenia patients and the effects of antipsychotic medication: a proton magnetic resonance spectroscopy study.

    Science.gov (United States)

    Tayoshi, Shin'Ya; Nakataki, Masahito; Sumitani, Satsuki; Taniguchi, Kyoko; Shibuya-Tayoshi, Sumiko; Numata, Shusuke; Iga, Jun-ichi; Ueno, Shu-ichi; Harada, Masafumi; Ohmori, Tetsuro

    2010-03-01

    Gamma-amino butyric acid (GABA) is thought to play a role in the pathophysiology of schizophrenia. High magnetic field proton magnetic resonance spectroscopy ((1)H-MRS) provides a reliable measurement of GABA in specific regions of the brain. This study measured GABA concentration in the anterior cingulate cortex (ACC) and in the left basal ganglia (ltBG) in 38 patients with chronic schizophrenia and 29 healthy control subjects. There was no significant difference in GABA concentration between the schizophrenia patients and the healthy controls in either the ACC (1.36+/-0.45 mmol/l in schizophrenia patients and 1.52+/-0.54 mmol/l in control subjects) or the ltBG (1.13+/-0.26 mmol/l in schizophrenia patients and 1.18+/-0.20 mmol/l in control subjects). Among the right handed schizophrenia patients, the GABA concentration in the ltBG was significantly higher in patients taking typical antipsychotics (1.25+/-0.24 mmol/l) than in those taking atypical antipsychotics (1.03+/-0.24 mmol/l, p=0.026). In the ACC, the GABA concentration was negatively correlated with the dose of the antipsychotics (rs=-0.347, p=0.035). In the ltBG, the GABA concentration was positively correlated with the dose of the anticholinergics (rs=0.403, p=0.015). To the best of our knowledge, this is the first study to have directly measured GABA concentrations in schizophrenia patients using (1)H-MRS. Our results suggest that there are no differences in GABA concentrations in the ACC or the ltBG of schizophrenia patients compared to healthy controls. Antipsychotic medication may cause changes in GABA concentration, and atypical and typical antipsychotics may have differing effects. It is possible that medication effects conceal inherent differences in GABA concentrations between schizophrenia patients and healthy controls. (c) 2009 Elsevier B.V. All rights reserved.

  17. The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

    Science.gov (United States)

    Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

    2014-08-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

  18. In vivo analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model

    Directory of Open Access Journals (Sweden)

    Mihoko Hagiwara

    2016-09-01

    Full Text Available We assessed electrophysiological effects of an atypical antipsychotic drug paliperidone in acute atrioventricular block rabbits. Intravenous administration of paliperidone at a clinically relevant dose (0.06 mg/kg hardly affected the QT interval or monophasic action potential (MAP duration, and the higher doses (0.6 and 6 mg/kg prolonged the QT interval and MAP duration. Meanwhile, premature ventricular contractions with R on T phenomenon were observed in 3 out of 6 animals at the middle dose, and torsades de pointes (TdP episodes were detected in 2 out of 6 animals at the high dose. Intravenous administration of its chemically related compound risperidone at a clinically relevant dose (0.03 mg/kg hardly affected the electrophysiological parameters, and the higher doses (0.3 and 3 mg/kg prolonged the QT interval and MAP duration. Meanwhile, the premature ventricular contractions with R on T were observed in 2 out of 6 animals at the middle dose, and TdP episodes were detected in 4 out of 6 animals at the high dose. These results suggest that paliperidone showed torsadogenic potential at supra-therapeutic doses, whose potency can be estimated to be equal or slightly subordinate in comparison with that of risperidone.

  19. Screening of cardiovascular risk factors in patients with schizophrenia and patients treated with antipsychotic drugs: are we equally exhaustive as with the general population?

    Science.gov (United States)

    Castillo-Sánchez, Miguel; Fàbregas-Escurriola, Mireia; Bergè-Baquero, Daniel; Fernández-SanMartín, MªIsabel; Goday-Arno, Albert

    2017-01-01

    Many studies have previously shown increased cardiovascular risk factors related to schizophrenia independently from the use of antipsychotic drugs. However, a poorer effort in clinical detection and management of cardiovascular risk in patients with severe mental illness could also explain these results. To test this hypothesis, we analyzed the differences in screening and incidence of cardiovascular risk factors between schizophrenia, non-schizophrenic patients on treatment with antipsychotic drugs (NS-TAD) and the general population. Data from adult subjects assessed by high-quality register general practitioners from 2006 to 2011 were extracted from the Catalonian SIDIAP database. The schizophrenia, NS-TAD, and control groups were compared in terms of measurements and incidence of diabetes, dyslipidemia, obesity, hypertension, and smoking. A total of 4911 patients in the schizophrenia group, 4157 in NS-TAD group, and 98644 in the control group were included. Schizophrenia patients were screened for dyslipidemia and diabetes more frequently than the control group, while for obesity or hypertension, they were screened equal to controls. Also, as compared to the control group, the NS-TAD group was more frequently screened for obesity with no differences in dyslipidemia and diabetes and less frequently for hypertension. Smoking was less frequently screened in both study groups. The incidence of all risk factors studied in both study groups was higher than or equal to the control group, except for hypertension, which had lower incidence. The lack of screening of risk factors does not appear decisive in the increased cardiovascular risk of patients diagnosed with schizophrenia seen in primary care. Studies evaluating the possible under diagnosis of the risk factors are required. Schizophrenia (SZ); Treatment with antipsychotic drugs (TAD); Cardiovascular risk factor/s (CVRF); Without schizophrenia but on therapy with antipsychotic drugs (NS-TAD); Defined Daily Dose

  20. The effect of zonisamide on antipsychotic-associated weight gain in patients with schizophrenia: a randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Ghanizadeh, Ahmad; Nikseresht, Mohammad Saeed; Sahraian, Ali

    2013-06-01

    Many patients with schizophrenia suffer from metabolic symptoms and weight gain in which predispose them to obesity, diabetes, and cardiovascular problems. This trial examines the efficacy and safety of zonisamide on weight and body mass index in patients with schizophrenia being administered with atypical antipsychotics. In this 10-week, double blind randomized placebo controlled clinical trial, forty one patients with schizophrenia diagnosed according to DSM-IV-TR criteria who were taking a stable dose of atypical antipsychotic are allocated into one of the two groups of zonisamide or placebo group. Weight, body mass index, waist circumference, and adverse effects were assessed. The two groups were not statistically different regarding baseline characteristics on age, gender, education, diagnosis, weight, body mass index, daily cigarette smoking, and the duration of illness. After 10 weeks, the patients in the placebo group had significantly gained weight, while the patients in the zonisamide group lost weight (mean=1.9, SD=2.2 versus mean=-1.1 kg, SD=1.4). The changes of body mass index in the two groups were significantly different. Body mass index decreased in the zonisamide group (mean=-0.3, SD=0.4) while it increased in the placebo group (mean=2.2, SD=6.9). There was a significance difference between the two groups regarding waist circumference at the end of trial (Pweight loss of patients with schizophrenia being treated with atypical antipsychotics. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for Adults with Learning Disabilities.

    Science.gov (United States)

    McNamara, Rachel; Randell, Elizabeth; Gillespie, David; Wood, Fiona; Felce, David; Romeo, Renee; Angel, Lianna; Espinasse, Aude; Hood, Kerry; Davies, Amy; Meek, Andrea; Addison, Katy; Jones, Glyn; Deslandes, Paul; Allen, David; Knapp, Martin; Thapar, Ajay; Kerr, Michael

    2017-08-01

    Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. A two-arm individually randomised double-blind placebo-controlled drug reduction trial. Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes

  2. The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, M B; Fuxe, K; Werge, T

    2002-01-01

    and lack of EPS in rodents could also be observed in non-human primates. We investigated the effects of CGS 21680 on behaviours induced by D-amphetamine and (-)-apomorphine in EPS-sensitized Cebus apella monkeys. CGS 21680 was administered s.c. in doses of 0.01, 0.025 and 0.05 mg/kg, alone...... and in combination with D-amphetamine and (-)-apomorphine. The monkeys were videotaped after drug administration and the tapes were rated for EPS and psychosis-like symptoms. CGS 21680 decreased apomorphine-induced behavioural unrest, arousal (0.01-0.05 mg/kg) and stereotypies (0.05 mg/kg) while amphetamine...... showed a functional anti-dopaminergic effect in Cebus apella monkeys without production of EPS. This further substantiates that adenosine A2A receptor agonists may have potential as antipsychotics with atypical profiles....

  3. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

    Science.gov (United States)

    Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2016-01-30

    Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Pharmacokinetic-pharmacodynamic modeling of antipsychotic drugs in patients with schizophrenia Part I : The use of PANSS total score and clinical utility

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    Background: To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU)

  5. Impact of the Pharma Economic Act on Diffusion of Innovation and Reduction of Costs in the Hungarian Prescription Drug Market (2007-2010).

    Science.gov (United States)

    Hren, Rok

    In this study, we examined the impact of the Pharma Economic Act, which was introduced in Hungary in 2007. We used detailed data on the Hungarian prescription drug market, which had been made publicly available by the authorities. We evaluated the effect of the Pharma Economic Act on both dynamic and static efficiencies and also on equity, which has been historically a controversial issue in Hungary. We analyzed the overall prescription drug market and statin and atorvastatin markets; as a proxy for determining dynamic efficiency, we examined the oncology drug market for some specific products (e.g., bortezomib) and the long-acting atypical antipsychotic drugs market. There is no denying that the authorities managed to control the overall prescription drug costs; however, they were still paying excessive rents for off-patent drugs. Examples of oncology and long-acting atypical antipsychotic drugs showed that the diffusion of innovation was on per-capita basis at least comparable to G-5 countries. While the share of out-of-pocket co-payments markedly increased and the reimbursement was lowered, the concurrent price decreases often meant that the co-payment per milligram of a given dispensed drug was actually lower than that before the Act, thereby benefiting the patient. It appears that strong mechanisms to control volume rather than price on the supply side (marketing authorization holders) contained the drug expenditure, while offering enough room to strive for innovation. Making data on prescription drug expenditures and associated co-payments publicly available is an item that should be definitely followed by the surrounding jurisdictions. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

  6. Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment

    Directory of Open Access Journals (Sweden)

    Rayees Ahmad Wani

    2015-01-01

    Full Text Available Background: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. Materials and Methods: Fifty patients (32 males and 18 females diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females was taken for comparison. Results were interpreted using American Diabetic Association criteria. Results: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. Conclusion: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

  7. Modulation of haloperidol-induced patterns of the transcription factor Nur77 and Nor-1 expression by serotonergic and adrenergic drugs in the mouse brain

    Science.gov (United States)

    Maheux, Jérôme; Vuillier, Laura; Mahfouz, Mylène; Rouillard, Claude; Lévesque, Daniel

    2015-01-01

    Different patterns of expression of the transcription factors of Nur77 and Nor-1 are induced following acute administration of typical and atypical antipsychotic drugs. The pharmacological profile of atypical antipsychotics suggests that serotonergic and/or adrenergic receptors might contribute to these reported differences. In order to test this possibility, we examined the abilities of serotonin 5-HT1A and 5-HT2A/2C, and α1- and α2-adrenergic receptor drugs to modify the pattern of Nur77 (NR4A1) and Nor-1 (NR4A3) mRNA expression induced by haloperidol. Various groups of mice were treated with either saline, DOI, a 5-HT2A/2C agonist, MDL11939, a 5-HT2A antagonist, 8-OH-DPAT, a 5-HT1A agonist, prazosin, an α1-adrenergic antagonist and idazoxan, an α2-adrenergic antagonist, alone or in combination with haloperidol. The 5-HT2A/2C agonist DOI alone significantly increased Nur77 expression in the medial striatum and nucleus accumbens. DOI reduced Nor-1 expression, while MDL11939 increased the expression of this transcript in the cortex. Prazosin reduced Nur77 expression in the dorsal striatum and nucleus accumbens. Interestingly, 8-OH-DPAT and MDL11939 partially prevented haloperidol-induced Nur77 up-regulation, while MDL11939 completely abolished Nor-1 expression in the striatum. In addition, MDL11939 decreased haloperidol-induced Nur77 and Nor-1 mRNA levels in the ventral tegmental area. On the contrary, idazoxan (α2 antagonist) consistently potentiated haloperidol-induced Nur77, but not Nor-1 mRNA levels in the striatum, whereas prazosin (α1 antagonist) remained without effect. Taken together, these results show the ability of a 5-HT1A agonist or a 5-HT2A antagonist to reduce haloperidol-induced Nur77 and Nor-1 striatal expression, suggesting that these serotonin receptor subtypes participate in the differential pattern of gene expression induced by typical and atypical antipsychotic drugs. PMID:21524335

  8. Onset of action of atypical and typical antipsychotics in the treatment of adolescent schizophrenic psychoses

    Czech Academy of Sciences Publication Activity Database

    Zedková, I.; Dudová, I.; Urbánek, Tomáš; Hrdlička, M.

    2011-01-01

    Roč. 32, č. 5 (2011), s. 667-670 ISSN 0172-780X Institutional research plan: CEZ:AV0Z70250504 Keywords : schizophrenia * antipsychotics * onset of action Subject RIV: AN - Psychology Impact factor: 1.296, year: 2011

  9. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Mizushima Jin

    2012-07-01

    Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  10. Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia.

    Science.gov (United States)

    Miura, Itaru; Shiga, Tetsuya; Katsumi, Akihiko; Kanno-Nozaki, Keiko; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2014-03-01

    Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia. Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography. There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores. There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Antipsychotic interventions in prodromal psychosis: safety issues.

    Science.gov (United States)

    Liu, Chen-Chung; Demjaha, Arsime

    2013-03-01

    In recent years, psychopharmacological intervention in prodromal psychosis, also known as the ultra-high risk (UHR) mental state for psychosis, has attracted much attention. Whilst it has been shown that antipsychotic use in UHR individuals may be effective in potentially delaying or even averting progression to frank psychosis, their use in subjects that do not necessarily convert to psychosis has raised considerable ethical concerns because of their adverse effects. Recent treatment guidelines for patients at UHR for psychosis recommend the use of antipsychotics only in exceptional conditions and with great precautions. To date only a few studies have investigated the use of antipsychotic medications in UHR patients and the potential benefits and risks related to their use in prodromal psychosis remain unclear. We review here all published studies that included UHR patients treated with antipsychotics, regardless of study design. These studies were all of second-generation antipsychotics, given that first-generation antipsychotics cannot be recommended because of their adverse drug reactions. We specifically examine the available descriptions of adverse reactions of the individual antipsychotic medication in each study and discuss the potential effects of various demographic and clinical factors that may impact on safety issues of pharmacological interventions in UHR patients. Clinical trials to date investigating potential benefits of antipsychotic treatments in preventing transition to psychosis were of relatively short duration and have involved a small number of patients. Whilst it appears that pharmacological intervention at this stage may be effective in both reducing the psychopathology and decreasing transition rates, and is potentially safe, in the absence of sufficient evidence-based knowledge to guide treatment, definitive clinical recommendations and guidelines cannot be derived. Certain adverse events take time to develop, such as metabolic syndrome

  12. Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

    Science.gov (United States)

    Zhang, Chen; Li, Ming

    2011-01-01

    Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

  13. Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine.

    Science.gov (United States)

    Zhang, Chen; Li, Ming

    2012-02-01

    Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL or OLZ for 5 consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated HAL or OLZ treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with HAL or OLZ did not show a stronger inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may develop an association with unconditional drug effects through a Pavlovian conditioning process. They may also serve as occasion setters to modulate the expression of sensitized responses. As antipsychotic sensitization mimics the clinical

  14. Combined use of electroconvulsive therapy and antipsychotics (both clozapine and non-clozapine in treatment resistant schizophrenia: A comparative meta-analysis

    Directory of Open Access Journals (Sweden)

    Saeed Ahmed

    2017-11-01

    Full Text Available Aim: To assess the relative efficacies of clozapine plus Electroconvulsive Therapy (ECT compared against non-clozapine typical and atypical antipsychotics plus ECT for the treatment of “Treatment Resistant Schizophrenia” (TRS. Primarily to assess if clozapine delivers a significant improvement over other antipsychotics when combined with ECT. Design: Major electronic databases were searched between 1990 and March 2017 for trials measuring the effects of either clozapine augmented ECT, other antipsychotic-augmented ECT, or both. After the systematic review of the data, a random-effects meta-analysis was conducted measuring the relative effect sizes of the different treatment regimens. Subjects: 1179 patients in 23 studies reporting the usage of ECT augmentation with antipsychotics. A total of 95 patients were tested with clozapine, and ECT (9 studies and 1084 patients were tested with non-clozapine antipsychotics (14 studies such as flupenthixol, chlorpromazine, risperidone, sulpiride, olanzapine, and loxapine with concurrent ECT treatment considered for systematic review. Of these, 13 studies reported pre and post-treatment scores were included in the meta-analysis. Main outcome measures: The main outcome measure was the presence and degree of both positive and negative psychotic symptoms, as measured by either of two standardized clinician administered tests, the Brief Psychiatric Rating Scale (BPRS, and the Positive and Negative Symptom Scale (PANSS. Results: The comparison of the different antipsychotics established the supremacy of ECT-augmented clozapine treatment against other typical and atypical antipsychotics. The Forest Plot revealed that the overall standard mean difference was 0.891 for non-clozapine studies and 1.504 for clozapine studies, at a 95% interval. Furthermore, the heterogeneity plots showed that while clozapine studies showed no significant heterogeneity, non-clozapine studies showed an I2 statistic value at 42

  15. Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.

    Science.gov (United States)

    McGrane, Ian R; Loveland, Joshua G; de Leon, Jose

    2017-01-01

    Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.

  16. Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

    Directory of Open Access Journals (Sweden)

    Haeberle Anne

    2012-09-01

    Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.

  17. Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects treated with antipsychotics.

    Science.gov (United States)

    Vassas, Thomas J; Burghardt, Kyle J; Ellingrod, Vicki L

    2014-01-01

    Patients with schizophrenia treated with antipsychotics often develop metabolic side effects including dyslipidemia. Antipsychotics potentially upregulate gene expression of a lipid metabolism pathway protein called SREBP via SREB transcription factors (SREBFs). Genetic variation within SREBF may contribute to dyslipidemias and lipid medication efficacy within schizophrenia. A cross-sectional study of 157 patients were genotyped for SREBF1 (rs11868035) and SREBF2 (rs1057217) variants, and assessed for fasting lipids. The cohort's mean age was 46.6 years, was 64% male and 86% were using atypical antipsychotics. When stratified by statin use, those receiving a statin and carrying the SREBF1 T allele exhibited higher total cholesterol levels (p = 0.01), triglyceride levels (p = 0.04) and low-density lipoprotein levels (p = 0.03). A regression analysis controlling for gender differences in lipids showed that the SREBF1 T allele and statin interaction remained only for total cholesterol levels (F[4,149] = 5.8; p < 0.0001). For schizophrenia individuals with the SREBF1 rs11868035 T allele, incomplete response to statin medications may be seen. Future investigations may allow for personalizing dyslipidemia treatment based on pharmacogenetics within schizophrenia.

  18. A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.

    Science.gov (United States)

    Kim, Eosu; Park, Dong-Wha; Choi, Song-Hee; Kim, Jae-Jin; Cho, Hyun-Sang

    2008-04-01

    Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.

  19. Prevalence of Antipsychotic Polypharmacy and Associated Factors among Outpatients with Schizophrenia Attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Siranesh Tesfaye

    2016-01-01

    Full Text Available Background. Despite recommendations by guidelines to avoid combinations of antipsychotics unless after multiple trials of antipsychotic monotherapy, it is quite a common practice to use combinations. This practice leads to unnecessary expenses and exposes the patient to severe drug adverse effects. Methods. An institution based cross-sectional study was conducted from April to May 2014. Systematic random sampling technique was used to select 423 study subjects. Logistic regression analysis was conducted to identify associated factors of antipsychotic polypharmacy among schizophrenia outpatients. Result. The overall prevalence of antipsychotic polypharmacy was found to be 28.2%. Extra pyramidal side effects (AOR = 2.80; 95% CI: 1.38, 5.71, repeated psychiatric hospitalization (AOR = 2.83; 95% CI: 1.45, 5.50, history of substance use (AOR = 2.82; 95% CI: 1.36, 5.88, longer duration of treatment (AOR = 2.10; 95% CI: 1.14, 3.87, and drug nonadherence (AOR = 1.84; 95% CI: 1.14, 2.98 were found to be significantly associated with antipsychotic polypharmacy. Conclusion. Prevalence of antipsychotic polypharmacy was found to be high among the current study participants. Individuals who had extra pyramidal side effects, admission, substance use, duration of treatment, and drug nonadherence were associated with antipsychotic polypharmacy.

  20. Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

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    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

  1. Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe

    2017-01-01

    A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she......-three hours after the suspected drug-facilitated sexual assault (DFSA), blood and urine samples were collected and the initial toxicological screening detected quetiapine. Confirmation and quantification by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) revealed...... a concentration of 0.007mg/kg quetiapine in blood and 0.19mg/l in urine. Six months after the DFSA, a hair sample was collected and segmental hair analysis was performed on four washed segments (0-3cm, 3-5cm, 5-7cm, and 7-9cm). The last segment contained 0.011ng/mg of quetiapine, whereas the other segments were...

  2. Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications.

    Science.gov (United States)

    Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

    2016-01-01

    The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system.

  3. O papel dos antipsicóticos atípicos no tratamento do transtorno bipolar: revisão da literatura The role of atypical antipsychotic agents in the treatment of bipolar disorder: a literature review

    Directory of Open Access Journals (Sweden)

    Acioly LT Lacerda

    2002-03-01

    Full Text Available Estudos recentes têm demonstrado que a eficácia do lítio é significativamente inferior à descrita pelos primeiros trabalhos, embora ainda seja a medicação de referência no tratamento do transtorno afetivo bipolar. Apesar de um perfil de segurança desfavorável, os antipsicóticos clássicos sempre apresentaram um papel importante no tratamento desse transtorno psiquiátrico, especialmente como coadjuvante em sua fase maníaca aguda. Os autores, utilizando informação obtida no Medline, fizeram uma revisão acerca do papel dos antipsicóticos atípicos no tratamento dos pacientes bipolares. Baseado nos dados da literatura, a olanzapina mostrou-se bastante eficaz no manejo da mania aguda, quando uma média de 63,5% dos pacientes apresentaram melhora significativa em estudos duplo-cego controlados, apresentando ganho de peso como único efeito colateral relevante. A clozapina e, mais ainda, a risperidona apresentaram dados menos consistentes, grande parte em função de deficiências metodológicas dos poucos estudos conduzidos até o presente estudo. Os dados preliminares relativos à eficácia desse grupo farmacológico nos quadros refratários e nos sintomas depressivos são promissores, mas ainda não definitivos. Em relação a seus efeitos potenciais como estabilizadores do humor, não existem evidências conclusivas oriundas de estudos controlados, mas há interesse considerável para realização de investigações em pacientes bipolares tratados com antipsicóticos atípicos por períodos de tempo mais prolongados. Pesquisas futuras poderão tornar mais claras essas possíveis características terapêuticas.Even though lithium is still the choice drug in the treatment of bipolar disorder, recent studies have shown that it has a significant lower efficacy than previously described in earlier studies. Despite its adverse side effects, typical antipsychotic agents have often had a prominent role in the treatment of this psychiatric

  4. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

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    Ye W

    2012-01-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

  5. Association between community pharmacy loyalty and persistence and implementation of antipsychotic treatment among individuals with schizophrenia.

    Science.gov (United States)

    Zongo, Frank E; Moisan, Jocelyne; Grégoire, Jean-Pierre; Lesage, Alain; Dossa, Anara Richi; Lauzier, Sophie

    2018-01-01

    Non-adherence is a major obstacle to optimal treatment of schizophrenia. Community pharmacists are in a key position to detect non-adherence and put in place interventions. Their role is likely to be more efficient when individuals are loyal to a single pharmacy. To assess the association between the level of community pharmacy loyalty and persistence with and implementation of antipsychotic drug treatment among individuals with schizophrenia. A cohort study using databases from the Quebec health insurance board (Canada) was conducted among new antipsychotic users insured by Quebec's public drug plan. Level of community pharmacy loyalty was assessed as the number of pharmacies visited in the year after antipsychotics initiation. Persistence was defined as having an antipsychotic supply in the user's possession on the 730 th day after its initiation and implementation as having antipsychotics in the user's possession for ≥80% of the days in the second year after antipsychotics initiation (among persistent only). Generalized linear models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (95%CI). 6,251 individuals were included in the cohort and 54.1% had their drug prescriptions filled in >1 pharmacy. When compared to those who had their prescriptions filled in a single pharmacy, those who had their prescriptions filled in ≥4 different pharmacies were 22% more likely to be non-persistent (aPR = 1.22; 95%CI = 1.10-1.37) and 49% more likely to have an antipsychotic for loyalty in the context of severe mental illness indicates that this healthcare organisation factor might be associated with antipsychotics persistence and implementation. Identification of individuals with low community pharmacy loyalty and initiatives to optimize community pharmacy loyalty could contribute to enhanced persistence and implementation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Oculomotor and neuropsychological effects of antipsychotic treatment for schizophrenia

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    Kristian S. Hill

    2009-04-01

    Full Text Available Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Anti psychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function. While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.

  7. Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast.

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    Elke Ericson

    2008-08-01

    Full Text Available To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac interfered with establishment of cell polarity, cyproheptadine (Periactin targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol and pimozide (Orap. Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.

  8. Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

    Science.gov (United States)

    DuMouchel, William; Fram, David; Yang, Xionghu; Mahmoud, Ramy A; Grogg, Amy L; Engelhart, Luella; Ramaswamy, Krishnan

    2008-01-01

    This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. There are consistent and substantial differences between atypical antipsychotic drugs in the

  9. Role of radiology in psychiatry: a review | Abiodun | East African ...

    African Journals Online (AJOL)

    ... significant differences in ventricular volume and medial temporal structures. ... Drug distribution can be imaged by MRS and this has shown brain lithium level to be ... atypical antipsychotic drugs such as risperidone and clozapine have high ...

  10. Fluvoxamine for aripiprazole-associated akathisia in patients with schizophrenia: a potential role of sigma-1 receptors

    Directory of Open Access Journals (Sweden)

    Hashimoto Kenji

    2010-03-01

    Full Text Available Abstract Background Second-generation antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPSs than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interplay of several neurotransmitter systems might play a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors are shown to regulate a number of neurotransmitter systems in the brain. Methods We report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the antipsychotic drug aripiprazole. Results The global score on the Barnes Akathisia Scale in the two patients with schizophrenia treated with aripiprazole decreased after fluvoxamine monotherapy. Conclusion Doctors may wish to consider fluvoxamine as an alternative approach in treating akathisia associated with antipsychotic drugs such as aripiprazole.

  11. Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

    Science.gov (United States)

    Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

    2018-04-01

    This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license information and package inserts of antipsychotics. The results indicate a need for further clinical pediatric studies and better harmonization between agencies regarding antipsychotic used in pediatrics.

  12. Weight gain associated with atypical and typical antipsychotics during treatment of adolescent schizophrenic psychoses: A retrospective study

    Czech Academy of Sciences Publication Activity Database

    Hrdlička, M.; Zedková, I.; Blatný, Marek; Urbánek, Tomáš

    2009-01-01

    Roč. 30, č. 2 (2009), s. 256-261 ISSN 0172-780X Institutional research plan: CEZ:AV0Z70250504 Keywords : schizophrenia * antipsychotics * weight gain Subject RIV: AN - Psychology Impact factor: 1.047, year: 2009

  13. Adjunctive Treatment with Asenapine Augments the Escitalopram-Induced Effects on Monoaminergic Outflow and Glutamatergic Neurotransmission in the Medial Prefrontal Cortex of the Rat

    Science.gov (United States)

    Björkholm, Carl; Frånberg, Olivia; Malmerfelt, Anna; Marcus, Monica M.; Konradsson-Geuken, Åsa; Schilström, Björn; Jardemark, Kent

    2015-01-01

    Background: Substantial clinical data support the addition of low doses of atypical antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) to rapidly enhance the antidepressant effect in treatment-resistant depression. Preclinical studies suggest that this effect is at least partly explained by an increased catecholamine outflow in the medial prefrontal cortex (mPFC). Methods: In the present study we used in vivo microdialysis in freely moving rats and in vitro intracellular recordings of pyramidal cells of the rat mPFC to investigate the effects of adding the novel atypical antipsychotic drug asenapine to the SSRI escitalopram with regards to monoamine outflow in the mPFC and dopamine outflow in nucleus accumbens as well as glutamatergic transmission in the mPFC. Results: The present study shows that addition of low doses (0.05 and 0.1 mg/kg) of asenapine to escitalopram (5 mg/kg) markedly enhances dopamine, noradrenaline, and serotonin release in the rat mPFC as well as dopamine release in the nucleus accumbens. Moreover, this drug combination facilitated both N-methyl-d-Aspartate (NMDA)– and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–induced currents as well as electrically evoked excitatory postsynaptic potentials in pyramidal cells of the rat mPFC. Conclusions: Our results support the notion that the augmentation of SSRIs by atypical antipsychotic drugs in treatment-resistant depression may, at least in part, be related to enhanced catecholamine output in the prefrontal cortex and that asenapine may be clinically used to achieve this end. In particular, the subsequent activation of the D1 receptor may be of importance for the augmented antidepressant effect, as this mechanism facilitated both NMDA and AMPA receptor-mediated transmission in the mPFC. Our novel observation that the drug combination, like ketamine, facilitates glutamatergic transmission in the mPFC may contribute to explain the rapid and potent antidepressant

  14. New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

    Directory of Open Access Journals (Sweden)

    Warren CG

    2013-05-01

    Full Text Available Calvert G Warren,1 Steven L Dubovsky1,21Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, USA; 2Departments of Psychiatry and Medicine, University of Colorado, Boulder, CO, USAAbstract: Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.Keywords: bipolar disorder, antipsychotic drug, mania, maintenance, sublingual

  15. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia.

    Science.gov (United States)

    Montejo, Ángel L; Arango, Celso; Bernardo, Miguel; Carrasco, José L; Crespo-Facorro, Benedicto; Cruz, Juan J; Del Pino, Javier; García Escudero, Miguel A; García Rizo, Clemente; González-Pinto, Ana; Hernández, Ana I; Martín Carrasco, Manuel; Mayoral Cleries, Fermin; Mayoral van Son, Jaqueline; Mories, M Teresa; Pachiarotti, Isabella; Ros, Salvador; Vieta, Eduard

    2016-01-01

    Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old

  17. Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use.

    Directory of Open Access Journals (Sweden)

    David Pickar

    Full Text Available Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively, mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.

  18. Genetic variations of PIP4K2A confer vulnerability to poor antipsychotic response in severely ill schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Harpreet Kaur

    Full Text Available Literature suggests that disease severity and neurotransmitter signaling pathway genes can accurately identify antipsychotic response in schizophrenia patients. However, putative role of signaling molecules has not been tested in schizophrenia patients based on severity of illness, despite its biological plausibility. In the present study we investigated the possible association of polymorphisms from five candidate genes RGS4, SLC6A3, PIP4K2A, BDNF, PI4KA with response to antipsychotic in variably ill schizophrenia patients. Thus in present study, a total 53 SNPs on the basis of previous reports and functional grounds were examined for their association with antipsychotic response in 423 schizophrenia patients segregated into low and high severity groups. Additionally, haplotype, diplotype, multivariate logistic regression and multifactor-dimensionality reduction (MDR analyses were performed. Furthermore, observed associations were investigated in atypical monotherapy (n = 355 and risperidone (n = 260 treated subgroups. All associations were estimated as odds ratio (OR and 95% confidence interval (CI and test for multiple corrections was applied. Single locus analysis showed significant association of nine variants from SLC6A3, PIP4K2A and BDNF genes with incomplete antipsychotic response in schizophrenia patients with high severity. We identified significant association of six marker diplotype ATTGCT/ATTGCT (rs746203-rs10828317-rs7094131-rs2296624-rs11013052-rs1409396 of PIP4K2A gene in incomplete responders (corrected p-value = 0.001; adjusted-OR = 3.19, 95%-CI = 1.46-6.98 with high severity. These associations were further observed in atypical monotherapy and risperidone sub-groups. MDR approach identified gene-gene interaction among BDNF_rs7103411-BDNF_rs1491851-SLC6A3_rs40184 in severely ill incomplete responders (OR = 7.91, 95%-CI = 4.08-15.36. While RGS4_rs2842026-SLC6A3_rs2975226 interacted synergistically in

  19. Relationship between the rs1414334 C/G polymorphism in the HTR2C gene and smoking in patients treated with atypical antipsychotics.

    Science.gov (United States)

    Rico-Gomis, José María; Palazón-Bru, Antonio; Triano-García, Irene; Mahecha-García, Luis Fabián; García-Monsalve, Ana; Navarro-Ruiz, Andrés; Villagordo-Peñalver, Berta; Martínez-Hortelano, Alicia; Gil-Guillén, Vicente Francisco

    2018-04-15

    An association has been found between the C allele of the rs1414334 polymorphism in the HTR2C gene and the metabolic syndrome in psychiatric patients. However, no study has yet evaluated whether this allele is associated with smoking. To assess this issue, therefore, we performed a cross-sectional study with a sample of 166 adult patients treated with atypical antipsychotics in 2012-2013 in a region of Spain. The primary variable was the presence of the C allele of the rs1414334 polymorphism in the HTR2C gene. Secondary variables were the number of pack-years (number of cigarettes per day x number of smoking years ÷ 20), age, gender, schizophrenia, years since diagnosis, metabolic syndrome criteria and SCORE. A stepwise binary logistic regression model was constructed to determine associations between primary and secondary variables and their area under the ROC curve (AUC) was calculated. Of the total sample, 33 patients (19.9%) had the C allele of the polymorphism analyzed. Mean cigarette consumption was 11.6 pack-years. The multivariate analysis showed the following factors as associated with the polymorphism: higher cigarette consumption, being a woman, and not having abdominal obesity. The AUC was 0.706. An association was found between increased cigarette consumption over the years and the presence of the C allele of the rs1414334 polymorphism in the HTR2C gene.

  20. Effects of Antipsychotics on Secular Mortality Trends in Patients With Alzheimer's Disease

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Valentin, Jan B; Lolk, Annette

    2018-01-01

    OBJECTIVE: To investigate secular changes in mortality rates between patients with Alzheimer's disease (AD) and the general population as well as changes in antipsychotic drug treatment and the association between drug treatment and mortality in patients with AD in Denmark during a 12-year study...

  1. Interventions for tic disorders: An overview of systematic reviews and meta analyses.

    Science.gov (United States)

    Yang, Chunsong; Hao, Zilong; Zhu, Cairong; Guo, Qin; Mu, Dezhi; Zhang, Lingli

    2016-04-01

    We conducted a comprehensive search and the overview included 22 systematic reviews (SRs) for treating tic disorders (TDs). Three SRs indicated typical antipsychotics (i.e., haloperidol, pimozide) were efficacious in the reduction of tic severity compared with placebo but with poor tolerability. Six SRs assessed the efficacy of atypical antipsychotics and indicated that atypical antipsychotics (i.e., risperidone, aripiprazole) could significantly improved tic symptoms compared with placebo or typical antipsychotics with less AEs. Four SRs indicated alpha adrenergic agonists (i.e., clonidine, guanfacine) could improve tic symptoms. Two SRs assessed the efficacy of antiepileptic drugs and indicated topiramate was a promising therapy. Six SRs evaluated the efficacy of behavior therapy and showed habit reversal therapy (HRT) and exposure and response prevention (ERP) were effective. One SR evaluated the efficacy deep brain stimulation (DBS) and indicated DBS is a promising treatment option for severe cases of TS. In conclusion, RCTs directly comparing different pharmacological treatment options are scarce. In practice, typical and atypical antipsychotics are often considered firstly while other pharmacological medications are suggested as alternatives in the case of treatment failure or contradictory outcomes. Behavioral therapies can be used either alone or in combination with medication. Copyright © 2016. Published by Elsevier Ltd.

  2. What is it like to take antipsychotic medication? A qualitative study of patients with first-episode psychosis.

    Science.gov (United States)

    Gray, R; Deane, K

    2016-03-01

    What is known on the subject? Antipsychotic drugs are an important part of treatment for most patients with first episode psychosis. We do not know much about what it is like to take these drugs from the patient's point of view. What this paper adds to existing knowledge? We talked to 20 young people with psychosis about their experiences of taking antipsychotic drugs. Patients relationship with medication was complex, young people found medication often to be both good and bad at the same time. We were interested in how seemingly trivial issues--colour, taste, size, name--could be very important to young people and could result in them stopping. What are the implications for practice? We think our study highlights the complicated internal struggles that people with first episode psychosis have with medication. Our study highlights how Nurses and Doctors need to try and better understand what it is like to take these drugs and work collaboratively with patients to support them to make informed choices about treatment. Low-dose antipsychotic medication is an important part of treatment for people experiencing a first episode of psychosis. Little is known about this group of patients' experiences of taking medication. A qualitative study of purposively sampled young people experiencing a first episode of psychosis was carried out. A mental health nurse working in the early psychosis team interviewed participants using a structured topic guide. Interviews were subjected to thematic analysis. Interviews were completed with 20 young people. Thematic analysis generated six themes: (1) the drugs do work, (2) the drugs don't work (as well as I'd like), (3) side effects, (4) the indirect effects of medication, (5) rage against the machine and (6) the not trivial issues about medication. Our overarching meta-theme was that young people's experience of taking antipsychotics was complex; medication was often considered good and bad at the same time. Our observations underpin

  3. An explorative study of school performance and antipsychotic medication.

    Science.gov (United States)

    van der Schans, J; Vardar, S; Çiçek, R; Bos, H J; Hoekstra, P J; de Vries, T W; Hak, E

    2016-09-21

    Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research.

  4. Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges

    Science.gov (United States)

    Salem, Haitham; Nagpal, Caesa; Pigott, Teresa; Teixeira, Antonio Lucio

    2017-01-01

    Background: Akathisia continues to be a significant challenge in current neurological and psychiatric practice. Prompt and accurate detection is often difficult and there is a lack of consensus concerning the neurobiological basis of akathisia. No definitive treatment has been established for akathisia despite numerous preclinical and clinical studies. Method: We reviewed antipsychotic-induced akathisia including its clinical presentation, proposed underlying pathophysiology, current and under investigation therapeutic strategies. Conclusion: Despite the initial promise that second generation antipsychotics would be devoid of akathisia effects, this has not been confirmed. Currently, there are limited therapeutic options for the clinical practice and the evidence supporting the most widely used treatments (beta blockers, anticholinergic drugs) is still absent or inconsistent. PMID:27928948

  5. Antipsychotic use is a risk factor for hyponatremia in patients with schizophrenia: a 15-year follow-up study.

    Science.gov (United States)

    Yang, Hang-Ju; Cheng, Wan-Ju

    2017-03-01

    Hyponatremia affects 10% of patients with chronic schizophrenia and can lead to severe consequences. However, the role of antipsychotics and other risk factors in hyponatremia occurrence has remained inconsistent. This study examined the association between antipsychotic use and hyponatremia occurrence in patients with schizophrenia. We utilized the National Health Insurance Research Database to follow 2051 patients with schizophrenia from 1998 to 2013. Among them, 137 (6.7%) developed hyponatremia. Sociodemographic characteristics, physical comorbidities, and psychiatric treatment experiences were compared between those who had hyponatremia and those who did not. A Cox proportional hazards model was used to examine the hazard ratios (HRs) of these characteristics. In patients with hyponatremia, the mean age at first hyponatremia occurrence was 54.7 ± 13.9 years, an average of 9.5 ± 4.0 years after schizophrenia diagnosis, and 32.9% of them were off antipsychotics before hyponatremia occurrences. Age at schizophrenia diagnosis (HR = 1.1), low-income household (HR = 2.4), comorbidities (HR = 1.2), and psychiatric admissions (HR = 1.04) were associated with the risks of hyponatremia. Compared with no antipsychotic use, atypical (HR = 2.1) and typical antipsychotics (HR = 3.1) were associated with an elevated risk of hyponatremia, after adjustment for age, sex, and physical comorbidities. Carbamazepine use (HR = 2.9) was also a significant risk factor for hyponatremia (p schizophrenia with polypharmacy should be monitored for hyponatremia occurrences. Clinicians should pay attention to the impact of poor living conditions on hyponatremia occurrence.

  6. Psychiatrists' Attitude and Use of Second-generation Antipsychotics for the Treatment of Schizophrenia in Taiwan.

    Science.gov (United States)

    Chen, C K; Su, H H; Sun, I W

    2017-09-01

    This survey aimed to understand the attitude of psychiatrists and their use of commonly prescribed second-generation antipsychotics (SGAs) for the treatment of schizophrenia in Taiwan. It also attempted to identify the factors that might influence their preference for selecting SGAs. Psychiatrists were interviewed face-to-face using a structured questionnaire. The questionnaire addressed various issues involved in the treatment of patients with schizophrenia, including the reasons for selecting SGAs, psychiatrists' level of satisfaction with commonly prescribed SGAs, and their current use of SGAs in clinical practice. Gender and age of the psychiatrists, and practice setting were not related to SGA selection. The selection of a SGA might be influenced by characteristics of the psychiatrist, properties of the drugs, and the healthcare insurance system. Most psychiatrists agreed that the performance of brand-name drugs was superior to that of generic drugs. Better symptom control, improvement in cognition, and higher tolerability were among the major factors considered by psychiatrists in Taiwan when prescribing antipsychotics. Selection of a SGA in Taiwan is potentially influenced by the characteristics of the psychiatrist, properties of the drug, and the healthcare insurance system. Efficacy and tolerability were among the major determining factors when prescribing antipsychotics for the treatment of patients with schizophrenia.

  7. Temporomandibular disorders in patients with schizophrenia using antipsychotic agents: a discussion paper

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2014-03-01

    Full Text Available Arão Nogueira de Araújo,1 Marion Alves do Nascimento,1 Eduardo Pondé de Sena,1,2 Abrahão Fontes Baptista3,4 1Postgraduate Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Biomorphology, Institute of Health Sciences, 4Postgraduate Program in Medicine and Health, Federal University of Bahia, Salvador, Brazil Abstract: Patients with psychiatric problems show a tendency to develop temporomandibular disorders (TMD. Particularly, patients with schizophrenia are quite likely to have signs and symptoms of TMD due to the impairment of their oral health, the use of antipsychotic drugs, and other general health problems. In nonschizophrenic populations, TMD have been considered as the main cause of nondental pain in the orofacial region, involving mechanisms associated with changes in masticatory activity at the cortical and neuromuscular levels. Individuals with schizophrenia do not usually complain of pain, and TMD is misdiagnosed in this population. In this paper, we aimed to review the clinical aspects of TMD in people with schizophrenia on antipsychotic drug therapy. Keywords: schizophrenia, temporomandibular joint, pain, antipsychotic agents

  8. New and emerging treatments for symptomatic tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Rana AQ

    2013-11-01

    Full Text Available Abdul Qayyum Rana,1–4 Zishan M Chaudry,5 Pierre J Blanchet6 1Parkinson's Clinic of Eastern Toronto and Movement Disorders Centre, Toronto, ON, Canada; 2Scarborough Memory Program, Toronto, ON, Canada; 3Journal of Parkinsonism and RLS, Toronto, ON, Canada; 4Bulletin of World Parkinson's Program, Toronto, ON, Canada; 5Saba University School of Medicine, The Bottom, Saba, Dutch Caribbean; 6Department of Stomatology, University of Montreal, Montreal, QC, Canada Abstract: The aim of this review is to assess new, emerging, and experimental treatment options for tardive dyskinesia (TD. The methods to obtain relevant studies for review included a MEDLINE search and a review of studies in English, along with checking reference lists of articles. The leading explanatory models of TD development include dopamine receptor supersensitivity, GABA depletion, cholinergic deficiency, neurotoxicity, oxidative stress, changes in synaptic plasticity, and defective neuroadaptive signaling. As such, a wide range of treatment options are available. To provide a complete summary of choices we review atypical antipsychotics along with resveratrol, botulinum toxin, Ginkgo biloba, tetrabenazine, clonazepam, melatonin, essential fatty acids, zonisamide, levetiracetam, branched-chain amino acids, drug combinations, and invasive surgical treatments. There is currently no US Food and Drug Administration-approved treatment for TD; however, prudent use of atypical antipsychotics with routine monitoring remain the cornerstone of therapy, with experimental treatment options available for further management. Keywords: tardive dyskinesia, first-generation antipsychotics, motor symptoms, schizophrenia, Parkinson's, atypical antipsychotics

  9. The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia

    Directory of Open Access Journals (Sweden)

    Stefanović Vesna

    2015-01-01

    Full Text Available Background/Aim. Immune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response. Methods. In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC, C-reactive protein (CRP, erythrocytes sedimentation rate (ESR and the elements of differential white blood cell counts (or the leukocyte formula: granulocytes (Gra, lymphocytes (Lym and monocytes (Mon, in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders “Dr Laza Lazarević” in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS was applied to measure the severity of psychopathology and response to the treatment. Results. During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (≥ 25% of the patients for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001. The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045. Conclusion. The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic

  10. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

    DEFF Research Database (Denmark)

    Vidarsdottir, Solrun; Roelfsema, Ferdinand; Streefland, Trea

    2009-01-01

    BACKGROUND: Treatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth...

  11. Risperidone in Children and Adolescents with Conduct Disorder: A Single-Center, Open-Label Study

    OpenAIRE

    Ercan, Eyüp Sabri; Kutlu, Ayşe; Çıkoğlu, Sibel; Veznedaroğlu, Baybars; Erermiş, Serpil; Varan, Azmi

    2003-01-01

    Background: Risperidone is one of the most commonly used atypical antipsychotic drugs in the treatment of children and adolescents. However, the data about its use in children and adolescents with conduct disorder (CD) are limited.

  12. Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia.

    Science.gov (United States)

    Kerns, J William; Winter, Jonathan D; Winter, Katherine M; Boyd, Terry; Etz, Rebecca S

    2018-01-01

    Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD. Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primary-care practice for at least 3 years in Northwestern Virginia. PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management. PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development. © Copyright 2018 by the American Board of Family Medicine.

  13. Erectile dysfunction in patients taking psychotropic drugs and treated with phosphodiesterase-5 inhibitors

    Directory of Open Access Journals (Sweden)

    Rossella Mazzilli

    2018-03-01

    Full Text Available Objectives: The aim of this study was to assess the prevalence of patients with Erectile Dysfunction (ED receiving psychotropic drugs, the impact of these drugs on hormonal profile, and the efficacy of PDE5-i in these patients. Materials and methods: We recruited 1872 patients referring for ED to our Andrology Unit. Assessment included serum testosterone, gonadotropins, TSH, prolactin, and PSA, and the IIEF-5 questionnaire for ED diagnosis. Inclusion criteria were age 21-75 years and IIEF-5 total score ≤ 21; exclusion criteria included hypogonadism, diabetes mellitus, previous prostatectomy, other medication intake, and ED diagnosis prior to psychotropic drug treatment. Efficacy was rated with the IIEF-5 (remission: total score ≥ 22. Results: The prevalence of ED patients treated with psychotropic drugs since ≥ 3 months was 9.5% (178/1872, subdivided according to the drugs used into: Group A, 16 patients treated with atypical antipsychotics (9.0%; Group B, 55 patients with benzodiazepines (30.9%; Group C, 33 patients with antidepressant drugs (18.5%; and Group D, 74 patients with multiple psychotropic drugs (41.6%. Patients in Group A were significantly younger than other groups (p < 0.05. The hormonal profile presented only higher prolactin level in patients treated with antipsychotics, alone or in combination (p < 0.05. Overall, 146 patients received PDE5-i. Remission rate, after three months of treatment, was significantly higher in Group B compared to C and D groups (p < 0.05. Conclusions: A substantial portion of patients receiving psychotropic drugs show ED. Sexual performance in these patients benefits from PDE5-i. Age, effects of psychiatric disorders, psychotropic drugs, and PDE5-i treatment modality accounted for variability of response in this sample.

  14. Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid

    Directory of Open Access Journals (Sweden)

    Markus K. Larsson

    2015-01-01

    Full Text Available Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6, olanzapine (2 mg/kg, n = 6, and clozapine (20 mg/kg, n = 6 or saline ( n = 6 for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.

  15. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence

    Directory of Open Access Journals (Sweden)

    Dayabandara M

    2017-08-01

    Full Text Available Madhubhashinee Dayabandara, Raveen Hanwella, Suhashini Ratnatunga, Sudarshi Seneviratne, Chathurie Suraweera, Varuni A de Silva Department of Psychiatry, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka Abstract: Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine. Weight increases rapidly in the initial period after starting antipsychotics. Patients continue to gain weight in the long term. Children appear to be particularly vulnerable to antipsychotic-induced weight gain. Tailoring antipsychotics according to the needs of the individual and close monitoring of weight and other metabolic parameters are the best preventive strategies at the outset. Switching to an agent with lesser tendency to cause weight gain is an option, but carries the risk of relapse of the illness. Nonpharmacologic interventions of dietary counseling, exercise programs and cognitive and behavioral strategies appear to be equally effective in individual and group therapy formats. Both nonpharmacologic prevention and intervention strategies have shown modest effects on weight. Multiple compounds have been investigated as add-on medications to cause weight loss. Metformin has the best evidence in this respect. Burden of side effects needs to be considered when prescribing weight loss medications. There is no strong evidence to recommend routine prescription of add-on medication for weight reduction. Heterogeneity of study methodologies and other

  16. [Prevention and Treatment of Common Acute Adverse Effects With Antipsychotic Use in Adults With Schizophrenia Diagnosis].

    Science.gov (United States)

    Arenas Borrero, Álvaro Enrique; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; Vélez Traslaviña, Ángela; Castro Díaz, Sergio Mario; Jaramillo González, Luis Eduardo; García Valencia, Jenny

    2014-01-01

    To determine the most adequate strategies for the prevention and treatment of the acute adverse effects of the use of antipsychotics. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. A systematic literature search was carried out. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The non-pharmacological interventions such as nutritional counseling by a nutritionist, exercise and psychotherapy are effective in preventing weight gain with the use of antipsychotics. (Kg Weight reduction in DM of -3.05 (-4.16, -1.94)). The antipsychotic change from olanzapine to aripiprazole showed weight loss and decreased BMI (decreased weight in KG DM -3.21 (-9.03, -2.61). The use of beta blockers was ineffective in reducing akathisia induced by antipsychotic; using as outcome the 50% reduction of symptoms of akathisia comparing beta-blockers with placebo RR was 1.4 (0.59, 1.83). It is recommended to make psychotherapeutic accompaniment and nutrition management of overweight for patients with weight gain. If these alternatives are ineffective is suggested to change the antipsychotic or consider starting metformin. For the management of drug-induced akathisia it is recommended to decrease the dose of the drug and the addition of lorazepam. It is recommended using 5mg biperiden IM or trihexyphenidyl 5mg orally in case of secondary acute dystonia and for the treatment of antipsychotic-induced parkinsonism to decrease the dose of antipsychotic or consider using 2 - 4mg/day of biperiden or diphenhydramine 50mg once daily. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  17. The influence of atypical antipsychotic drugs on sexual function

    OpenAIRE

    Just, Marek J

    2015-01-01

    Marek J Just Department of General and Endocrine Surgery, Piekary Medical Centre, Piekary Slaskie, Poland Abstract: Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido), physiological arousal (lubrication/erection), orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to di...

  18. Relationship of symptomatology, gender, and antipsychotic drug treatment with plasma homovanillic acid in schizophrenia.

    Science.gov (United States)

    Zhang, Z J; Reynolds, G P; Ramchand, C; Peet, M; Shah, S

    2001-01-01

    To study the role of dopamine neurotransmission in schizophrenia and its drug treatment by assessing the relationship of plasma homovanillic acid (pHVA), a major central dopamine metabolite to various clinical parameters in schizophrenic patients. pHVA was measured by high-performance liquid chromatography with electrochemical detection in a large cohort of both medicated and unmedicated DSM-IV schizophrenic patients. Prior to the measurement of pHVA, the patients were rated on the schedule for the assessment of positive and negative symptoms (PANSS). (1) pHVA in 46 patients receiving antipsychotic drugs was decreased, and in 58 drug-free patients increased, (7.4+/-2.7) microg/L and (10+/-4) microg/L compared with a matched control group (9 microg/L+/-3 microg/L, n=62) (ANOVA F=8.57, df=2, P pHVA was higher in the patients with a more negative symptom profile. (2) No significant correlation of pHVA with overall SAPS or SANS scores was apparent in the drug-free patients, although within the SANS subscales, a significant relationships to anhedonia-asociality (r=0.32, P pHVA with negative symptoms (r=0.42, P < 0.05) while females showed no significant relationship with any PANSS subscales. The results suggest that an increased dopaminergic metabolism is apparent in (male) schizophrenic patients with predominantly negative symptoms, supporting reports that this change in neuronal activity may be related to the neuropathological abnormalities seen in the disease, which may differ between males and females. Such neuronal deficits of developmental origin may thus result in an elevation/disinhibition of central dopamine metabolism in schizophrenia.

  19. Risperidone long-acting injection: a review of its long term safety and efficacy

    Directory of Open Access Journals (Sweden)

    Michael K Rainer

    2008-08-01

    Full Text Available Michael K RainerMemory-Clinic and Psychiatric Department, Donauspital, Vienna, AustriaAbstract: A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low.Keywords: risperidone, schizophrenia, psychotic disorders, patient compliance; delayed-action preparations, injections, intramuscular

  20. Brain Connectivity Studies in Schizophrenia: Unravelling the Effects of Antipsychotics

    DEFF Research Database (Denmark)

    Nejad, A.B.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte Yding

    2012-01-01

    Impaired brain connectivity is a hallmark of schizophrenia brain dysfunction. However, the effect of drug treatment and challenges on the dysconnectivity of functional networks in schizophrenia is an understudied area. In this review, we provide an overview of functional magnetic resonance imaging...... studies examining dysconnectivity in schizophrenia and discuss the few studies which have also attempted to probe connectivity changes with antipsychotic drug treatment. We conclude with a discussion of possible avenues for further investigation....

  1. Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior.

    Science.gov (United States)

    Tang, Yan; Chang, Chung-Chou H; Lave, Judith R; Gellad, Walid F; Huskamp, Haiden A; Donohue, Julie M

    2016-03-01

    Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOSTM database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to 10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties

  2. Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on Agitation in Nursing Home Residents With Alzheimer Dementia.

    Science.gov (United States)

    Viscogliosi, Giovanni; Chiriac, Iulia Maria; Ettorre, Evaristo

    2017-09-01

    To assess efficacy and safety of citalopram compared to quetiapine and olanzapine for the treatment of agitation in patients with Alzheimer disease (AD). Longitudinal, 6-month study. Nursing home (NH). 75 NH residents with AD and agitation, randomized to citalopram (n = 25), quetiapine (n = 25), or olanzapine (n = 25). Changes in Neuropsychiatric Inventory (NPI) agitation subscale score and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) were used to assess treatment efficacy. Participants were surveilled for adverse health outcomes. Citalopram treatment (30±5.8 mg/d) resulted in similar 6-month efficacy compared to both quetiapine (94.0±40.4 mg/d) and olanzapine (5.2±1.6 mg/d), lower occurrence of falls than olanzapine [odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.97, P = .012], lower incidence of orthostatic hypotension than both quetiapine (OR = 0.80, 95% CI = 0.66-0.95, P = .032) and olanzapine (OR = 0.75, 95% CI = 0.69-0.91, P = .02), and less all-cause hospitalizations than both quetiapine (OR = 0.92, 95% CI = 0.88-0.95, P = .016) and olanzapine (OR = 0.78, 95% CI = 0.64-0.92, P = .004), after multiple adjustment for potentially confounding variables. No differences were observed for cognitive and functional decline, QTc prolongation, and infections. Citalopram resulted in similar efficacy and less adverse outcomes when compared to 2 atypical antipsychotics for treatment of agitation in NH residents with AD. Replication of these findings and assessment of long-term efficacy and safety of citalopram for treatment of neuropsychiatric symptoms in dementia are needed. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  3. Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011.

    Science.gov (United States)

    Guthrie, Bruce; Clark, Stella A; Reynish, Emma L; McCowan, Colin; Morales, Daniel R

    2013-01-01

    Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact. Segmented regression time-series analysis 2001-2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing. The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI -6.6 to -5.2) and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs. The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling

  4. Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder.

    Directory of Open Access Journals (Sweden)

    Hidehiro Umehara

    Full Text Available Selective serotonin reuptake inhibitors (SSRI are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD, while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics.We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS to examine the combined effects of genetic variants on the clinical response in OCD.While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses.Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.

  5. More than 25 years of genetic studies of clozapine-induced agranulocytosis

    NARCIS (Netherlands)

    With, S.A.J. de; Pulit, S.L.; Staal, W.G.; Kahn, R.S.; Ophoff, R.A.

    2017-01-01

    Clozapine is one of the most effective atypical antipsychotic drugs prescribed to patients with treatment-resistant schizophrenia. Approximately 1% of patients experience potential life-threatening adverse effects in the form of agranulocytosis, greatly hindering its applicability in clinical

  6. Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists' survey in India.

    Science.gov (United States)

    Gundugurti, Prasad Rao; Nagpal, Rajesh; Sheth, Ashit; Narang, Prashant; Gawande, Sonal; Singh, Vikram

    2017-12-01

    Schizophrenia is associated with functional challenges for patients; relapses in schizophrenia may lead to increased treatment costs and poor quality of life. This SUSTAIN-I study was conducted to establish psychiatrists' perspective on impact of long-acting injectables (LAIs) antipsychotics on the socio-economic and functional burden of schizophrenia. This cross-sectional, survey-based study was conducted in 5 cities in India. Psychiatrists (≥5years of experience) working in clinics, psychiatric, government hospitals and rehabilitation centers were included and administered a specially designed questionnaire to elicit information on their clinical practice and prescription patterns. Perceived treatment costs for LAI versus oral antipsychotic treatments (OATs) and relapse rates were assessed. Descriptive statistics were used to summarize results. Total 31 physicians completed this survey. In acute phase, OAT prescription was higher whereas chronic patients were treated with either OATs or LAIs. Treatment with LAIs was the preferred treatment in 9% of chronic cases. Reduced relapse rates were observed with LAI treatment: 12% patients on LAIs relapsed as compared with 60% patients on OATs. Monthly medication cost for oral medications was lower ($8-$17) than short-acting injectables ($22-$50). For chronic cases, atypical antipsychotics cost (oral: $11.7-25, LAI: $150-167) was higher than typical antipsychotics (oral: $4-5, LAI: $5-25). Of the total expenses incurred, cost for hospital admissions was the largest component (78%). Despite enhanced treatment adherence and potential to lower risk of rehospitalizations from relapse, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Safety and effectiveness of drug therapy for the acutely agitated patient (Part I

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone. Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5 and Fridericia

  8. Antipsychotics for fibromyalgia in adults.

    Science.gov (United States)

    Walitt, Brian; Klose, Petra; Üçeyler, Nurcan; Phillips, Tudor; Häuser, Winfried

    2016-06-02

    This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms. To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults. We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors. We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults. We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the

  9. Relationship between xerostomia and psychotropic drugs in patients with schizophrenia: evaluation using an oral moisture meter.

    Science.gov (United States)

    Okamoto, A; Miyachi, H; Tanaka, K; Chikazu, D; Miyaoka, H

    2016-12-01

    Patients with schizophrenia are most commonly treated with antipsychotic medications, often with the addition of anxiolytics. This study used an oral moisture meter to evaluate xerostomia in patients with schizophrenia taking typical and atypical antipsychotics, anxiolytics and non-psychotropic medications. Patients diagnosed with schizophrenia according to ICD-10 criteria in the Department of Psychiatry, Kitasato University East, and affiliated hospitals were studied. All patients were on psychotropic medications. Patients with diseases associated with xerostomia, such as Sjögren's syndrome I, were excluded. A total of 127 patients were enrolled. Mean oral moisture was 27·81 ± 2·27% (normal, ≥30·0%). A significant association was observed between objective oral moisture and the subjective sense of dry mouth. Multivariate analysis revealed a negative correlation between the number of antipsychotics and, especially, anxiolytics, and the degree of oral moisture. Drug dosages themselves were not significantly correlated with dry mouth. These findings suggest that objective oral moisture measurements show decreased moisture in patients on these medications and that the degree of moisture shows a greater negative correlation with the number, as opposed to the dosages, of psychotropic drugs administered. When patients with schizophrenia visit a dental clinic, it is important for the dentist to accurately assess the degree of oral moisture and to determine the medications being taken. Based on these findings of the association of polypharmacy with xerostomia, dentists are encouraged to inform the psychiatrist of the need to actively manage patients' xerostomia. © 2016 John Wiley & Sons Ltd.

  10. The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease.

    Science.gov (United States)

    Creese, Byron; Da Silva, Miguel Vasconcelos; Johar, Iskandar; Ballard, Clive

    2018-05-21

    Antipsychotics have long been the mainstay of treatment for agitation and psychosis in Alzheimer's disease. Despite their current use successive studies have shown that they only confer a modest benefit which must be balanced against their well-established serious side effects (extrapyramidal symptoms, stroke, accelerated cognitive decline and mortality). Areas covered: This review outlines the current guidance on antipsychotic usage and the evidence of their continued usage against a backdrop of emerging pharmacological treatments and an increasing emphasis on the importance of non-pharmacological interventions. Expert commentary: The current justification for antipsychotic use in the context of the changing landscape of prescribing and provide a view on the most promising alternative candidates to this class of drug are appraised.

  11. Bitropic D3 Dopamine Receptor Selective Compounds as Potential Antipsychotics.

    Science.gov (United States)

    Luedtke, Robert R; Rangel-Barajas, Claudia; Malik, Mahinder; Reichert, David E; Mach, R H

    2015-01-01

    Neuropsychiatric disorders represent a substantial social and health care issue. The National Institutes of Health estimates that greater than 2 million adults suffer from neuropsychiatric disorders in the USA. These individuals experience symptoms that can include auditory hallucinations, delusions, unrealistic beliefs and cognitive dysfunction. Although antipsychotic medications are available, suboptimal therapeutic responses are observed for approximately one-third of patients. Therefore, there is still a need to explore new pharmacotherapeutic strategies for the treatment of neuropsychiatric disorders. Many of the medications that are used clinically to treat neuropsychiatric disorders have a pharmacological profile that includes being an antagonist at D2-like (D2, D3 and D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved in a variety of neuronal circuits that include movement coordination, cognition, emotion, affect, memory and the regulation of prolactin. Consequently, antagonism at D2-like receptors can also contribute to some of the adverse side effects associated with the long-term use of antipsychotics including the a) adverse extrapyramidal symptoms associated with the use of typical antipsychotics and b) metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective compounds might represent an alternative strategy for the treatment of the symptoms of schizophrenia. In this review we discuss a) how bitropic Nphenylpiperazine D3 dopamine receptor selective compounds have been developed by modification of the primary (orthosteric) and secondary (allosteric or modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding selectivity ratios and b) the functional selectivity of these compounds. Examples of how these compounds might be

  12. Antipsychotic Management of Schizoaffective Disorder: A Review.

    Science.gov (United States)

    Lindenmayer, Jean-Pierre; Kaur, Amandeep

    2016-04-01

    Schizoaffective disorder (SAD) is an incapacitating illness that presents clinicians with challenges in terms of both its diagnosis and its psychopharmacological management. Most studies conducted on the psychopharmacological treatment of SAD also include patients with schizophrenia or other psychotic illnesses, thereby providing an unspecific view to the clinician as to the best way of treating patients with SAD. The objective of this article is to review studies on evidence-based treatment of patients with SAD. We conducted a systematic literature search in MEDLINE/PubMed for full-text studies in the English language using the terms 'Schizoaffective and treatment' or 'antipsychotic schizoaffective'. Our review found relatively few studies with either an active comparator or placebo that examined the efficacy of antipsychotics for patients with SAD without an admixture of patients with schizophrenia. Only oral paliperidone extended release (ER), paliperidone long-acting injection (LAI), and risperidone have been shown to be effective and safe in reducing psychotic as well as affective components in acutely ill SAD patients in controlled studies. Paliperidone ER and LAI have also been shown to be efficacious in the maintenance treatment phase of SAD patients. While no supportive data exist, it is possible that other atypical antipsychotics may have similar efficacy to the two mentioned above. We conclude with a number of research recommendations for the study of treatment options for patients with SAD. First, there is a need for studies with patients specifically diagnosed with SAD for both the acute and the maintenance phase. The sample size needs to be adequate to allow a primary analysis of efficacy and to allow for analysis of the SAD subtypes: depressed and bipolar. Another recommendation is the need for studies of patients with SAD stratified into patients with and without mood stabilizers or antidepressants to allow the examination of the adjunctive role of

  13. Pattern of Psychotropic Drug Prescription in the Elderly with Chronic Schizophrenia

    Directory of Open Access Journals (Sweden)

    Mohamad Reza Khodaei Ardakani

    2013-04-01

    Full Text Available Objectives: Psychotropic drug use in the elderly with chronic schizophrenia is an important issue in the field of psychiatry. The main goal of this study was to clarify the pattern of such drug use in these patients, in order to consider such therapy plan and focus on its cost attributing measures, for a more reasonable quality of care program. Methods: In this descriptive study, participants included 52 elderly patients at Tehran’s Razi Mental Hospital who had chronic schizophrenia in the residual phase. Selected patients were taking at least two psychotropic drugs equivalent to 500mg Chlorpromazine. We prepared the list of the drugs used by completing the pre-designed questionnaire charts. Data were analyzed with SPSS 17. Results: In one case (1.92% the entries were Risperidone, Chlorpromazine, Fluphenazine Decanoate, & Thiothixene. In 11 cases (21.2% there were three entries and in 40 cases (76.8% there were two. The Chlorpromazine equivalent dose in each group ranged from the lowest dose (750 mg to the highest (5600 mg. The highest Chlorpromazine dose (5600 mg equivalent per milligram belonged to the four entries of (Risperidone, Chlorpromazine, Fluphenazine Decanoate & Thiothixene. The lowest Chlorpromazine dose (750 mg was seen in 3 entries of Risperidone, Chlorpromazine & Fluphenazine Decanoate. Discussion: There was a high prevalence of using more than two psychotropic medications from the first atypical antipsychotic category. Less frequently, the second and the third typical antipsychotics were used. We recommend further research into more feasible patterns of psychotropic prescriptions, lowering the amount of medication use and considering their cost-benefits in the elderly with chronic schizophrenia.

  14. Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription

    Directory of Open Access Journals (Sweden)

    Thomas J Reilly

    2017-03-01

    Full Text Available Objectives: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. Methods: We present a case report of a patient who developed this syndrome with various sequelae. Results: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. Conclusions: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

  15. Quetiapine in overdosage : a clinical and pharmacokinetic analysis of 14 cases

    NARCIS (Netherlands)

    Hunfeld, N G M; Westerman, E M; Boswijk, D J; de Haas, J A M; van Putten, M J A M; Touw, D J

    Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported

  16. Antipsychotic medication for early episode schizophrenia

    Science.gov (United States)

    Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

    2014-01-01

    Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications

  17. Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, D

    2014-01-01

    INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative...... allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently...

  18. Treatment patterns and clinical characteristics prior to initiating depot typical antipsychotics for nonadherent schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Montgomery William

    2009-07-01

    Full Text Available Abstract Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314. Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4% who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests, recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a

  19. Incident users of antipsychotics

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kruse, Marie

    2016-01-01

    PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine...

  20. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence

    Directory of Open Access Journals (Sweden)

    Cathrin Rohleder

    2016-11-01

    Full Text Available There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC, cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial had been conducted and demonstrated that cannabidiol exerts antipsychotic properties in acute schizophrenia comparable to the antipsychotic drug amisulpride accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. However, a plethora of mechanisms of action has been suggested, but their potential relevance for the antipsychotic effects of cannabidiol needs still to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

  1. Central and Peripheral Mechanisms of Antipsychotic Medication-Induced Metabolic Dysregulation

    Science.gov (United States)

    2016-10-01

    may also significantly contribute to our fundamental understanding of obesity and lead to novel treatments. Since APD-induced metabolic disturbances...York, NY 10032 Department of Psychology , Yeshiva University, New York, NY 10016 Sponsor: Jonathan A. Javitch Background: Antipsychotic drugs...Zachary Freyberg Departments of Psychiatry, Pharmacology & Medicine, Columbia University, New York, NY 10032 Department of Psychology , Yeshiva

  2. Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011.

    Directory of Open Access Journals (Sweden)

    Bruce Guthrie

    Full Text Available Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact.Segmented regression time-series analysis 2001-2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing.The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI -6.6 to -5.2 and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs.The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates

  3. Superior effects of quetiapine compared with aripiprazole and iloperidone on MK-801-induced olfactory memory impairment in female mice.

    Science.gov (United States)

    Mutlu, Ahmet; Mutlu, Oguz; Ulak, Guner; Akar, Furuzan; Kaya, Havva; Erden, Faruk; Tanyeri, Pelin

    2017-05-01

    Cognitive dysfunction is commonly observed in schizophrenic patients and the administration of antipsychotic treatments results in different outcomes. Although the typical antipsychotic treatments, such as haloperidol, appear to be unable to improve cognition dysfunction, the atypical antipsychotic drugs (quetiapine, aripiprazole and iloperidone) exert a beneficial effect. The purpose of the current study was to investigate the effects of atypical antipsychotics on olfactory memory in mice, utilizing the social transmission of food preference (STFP) tests to evaluate the effects of drugs on MK-801-induced cognitive dysfunction. Female BALB/c mice were treated with quetiapine (5 and 10 mg/kg), aripiprazole (3 and 6 mg/kg), iloperidone (0.5 and 1 mg/kg) or MK-801 (0.1 mg/kg) alone or concurrently prior to retention sessions of STFP tests. In the STFP tests, quetiapine (10 mg/kg; P<0.05), aripiprazole (3 and 6 mg/kg; P<0.01 and P<0.001, respectively), iloperidone (0.5 and 1 mg/kg; P<0.01 and P<0.001, respectively) and MK-801 (P<0.001) significantly decreased cued/total food eaten (%). Quetiapine (5 mg/kg; P<0.05) significantly increased MK-801-induced decreases in cued/total food eaten (%), while aripiprazole and iloperidone demonstrated no significant effects. The results revealed that all of the drugs disturbed olfactory memory in the naive mice; however, only quetiapine reversed MK-801-induced memory impairment in the STFP test.

  4. Emerging role of aripiprazole for treatment of irritability associated with autistic disorder in children and adolescents.

    Science.gov (United States)

    Stachnik, Joan; Gabay, Michael

    2010-01-01

    Autistic disorder is a largely misunderstood and difficult to treat neurodevelopmental disorder. Three core domains of functioning are affected by autistic disorder, ie, socialization, communication, and behavior. Signs of autistic disorder may be present early, but are frequently overlooked, resulting in a delay in its diagnosis and a subsequent delay in treatment. No one definitive therapy is available, and treatment consists of early educational and behavioral interventions, as well as drug therapy. Atypical antipsychotics have often been used in the treatment of autistic disorder to target irritability, aggression, and self-injurious behavior, all of which can interfere with other aspects of treatment. One atypical antipsychotic, aripiprazole, has recently been approved for treatment of irritability associated with autistic disorder. Based on the results from two randomized, controlled trials, with efficacy data from nearly 300 patients, treatment with aripiprazole was associated with reductions in irritability, global improvements in behavior, and improvements in quality of life from both the patient and caregiver perspectives. Dosage of aripiprazole ranged from 5 mg to 15 mg per day. Aripiprazole was well tolerated during clinical trials, with most adverse events considered mild or moderate. Clinically relevant weight gain occurred in about 30% of patients given aripiprazole, although when compared with other atypical antipsychotics, aripiprazole appears to have fewer metabolic effects and a lower risk of weight gain. However, pediatric patients taking any atypical antipsychotic should be carefully monitored for potential adverse events, because the long-term effects of antipsychotic therapy in this population are not well known. When used appropriately, aripiprazole has the potential to be an effective treatment for children with autistic disorder to improve irritability and aggressive behavior and improve quality of life.

  5. Dyslipidaemia and Medical Outcome (Health Related Quality of Life in Patients with Schizophrenia Taking Antipsychotics in Enugu, Nigeria

    Directory of Open Access Journals (Sweden)

    Emmanuel Omamurhomu Olose

    2017-01-01

    Full Text Available Aim. Determine association between use (and type of antipsychotics and dyslipidaemia in newly diagnosed schizophrenia patients attending Federal Neuropsychiatric Hospital, Enugu. Methods. From sixty antipsychotic naive patients with schizophrenia and sixty first-degree relatives matched for gender and age, fasting blood lipid profiles were measured at baseline and after twelve weeks. Medical Outcome Study Short Form General Health Survey was administered to patients on both occasions. Fasting lipid profile changes of both groups were compared. Results. Mean endpoint of total cholesterol (TC, low density lipoprotein (LD, and triglycerides (TG in mmol/l for cases was significantly higher than initial values (TC 4.5 versus 4.3, t=4.3, p<0.0001, (LDL 2.8 versus 2.6, t=14.3, p<0.0001, and (TG 1.3 versus 1.0, t=12.1, p<0.0001. Mean endpoint of high density lipoprotein (HDL in mmol/l for cases was significantly lower than initial values (1.1 versus 1.2, t=12.1, p<0.0001. Prevalence of dyslipidaemia for cases was 13%. Mean endpoint of TC, LDL, TG, and HDL in mmol/l for controls was not significantly different from initial values (TC 4.30 versus 4.27, t=1.09, p=0.279, (LDL 2.49 versus 2.46, t=1.28, p=0.205, (TG 0.96 versus 0.94, t=1.27, p=0.207, and (HDL 1.37 versus 1.38, t=1.61, p=0.113. Subjects on atypical antipsychotics had higher risk for dyslipidaemia. Conclusion. Use of antipsychotics was significantly associated with dyslipidaemia.

  6. Central administration of an orexin receptor 1 antagonist prevents the stimulatory effect of Olanzapine on endogenous glucose production

    NARCIS (Netherlands)

    Girault, Elodie M.; Foppen, Ewout; Ackermans, Mariëtte T.; Fliers, Eric; Kalsbeek, Andries

    2013-01-01

    Atypical antipsychotic drugs such as Olanzapine (Olan) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. It has been shown that peripheral injections of Olan activate neurons in

  7. Antipsychotic treatment among youth in foster care.

    Science.gov (United States)

    Dosreis, Susan; Yoon, Yesel; Rubin, David M; Riddle, Mark A; Noll, Elizabeth; Rothbard, Aileen

    2011-12-01

    Despite national concerns over high rates of antipsychotic medication use among youth in foster care, concomitant antipsychotic use has not been examined. In this study, concomitant antipsychotic use among Medicaid-enrolled youth in foster care was compared with disabled or low-income Medicaid-enrolled youth. The sample included 16 969 youths younger than 20 years who were continuously enrolled in a Mid-Atlantic state Medicaid program and had ≥1 claim with a psychiatric diagnosis and ≥1 antipsychotic claim in 2003. Antipsychotic treatment was characterized by days of any use and concomitant use with ≥2 overlapping antipsychotics for >30 days. Medicaid program categories were foster care, disabled (Supplemental Security Income), and Temporary Assistance for Needy Families (TANF). Multicategory involvement for youths in foster care was classified as foster care/Supplemental Security Income, foster care/TANF, and foster care/adoption. We used multivariate analyses, adjusting for demographics, psychiatric comorbidities, and other psychotropic use, to assess associations between Medicaid program category and concomitant antipsychotic use. Average antipsychotic use ranged from 222 ± 110 days in foster care to only 135 ± 101 days in TANF (P foster care only and 24% in foster care/adoption compared with youths in the foster care system.

  8. Association Study of 60 Candidate Genes with Antipsychotic-induced Weight Gain in Schizophrenia Patients.

    Science.gov (United States)

    Ryu, S; Huh, I-S; Cho, E-Y; Cho, Y; Park, T; Yoon, S C; Joo, Y H; Hong, K S

    2016-03-01

    This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug-Related Eating Behavior Questionnaire. No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (PGHRL showed suggestive evidence of association with not only weight gain (P=0.001) but also appetite change (P=0.042). Patients carrying the GG genotype of rs696217 exhibited higher increase in both BMI and appetite compared to patients carrying the GT/TT genotype. Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients. © Georg Thieme Verlag KG Stuttgart · New York.

  9. The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

    Science.gov (United States)

    Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

    2012-03-01

    Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

  10. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

  11. Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

    Science.gov (United States)

    Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

    2010-02-01

    A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Update on the management of symptoms in schizophrenia: focus on amisulpride

    Directory of Open Access Journals (Sweden)

    Ann M Mortimer

    2009-05-01

    Full Text Available Ann M MortimerDepartment of Psychiatry, Hertford Building, The University of Hull, Cottingham Road, Hull HU6 7RX, United KingdomAbstract: Amisulpride is an atypical antipsychotic drug with a unique receptor pharmacology which is dose dependent. It is a standard treatment in dysthymia as well as in psychosis. Amisulpride is efficacious, effective and well tolerated in positive symptoms of schizophrenia: there is extensive evidence that it treats negative symptoms when given in low doses, although relative lack of EPS and an antidepressant effect may contribute. In first-episode patients amisulpride is an option, although there is little comparative work available. Amisulpride has the best evidence as an effective adjunct to clozapine treatment. Regarding intellectual function, amisulpride appears cognitive sparing but the clinical relevance of this remains obscure. There is evidence that amisulpride can improve social function but again there is little comparative work to demonstrate any particular advantages. Regarding the current conventional versus atypical antipsychotic controversy, amisulpride did better in switching studies and meta-analyses than in the single large pragmatic randomized trial reported to date. It is a versatile drug, and may offer advantages over other atypical antipsychotic drugs in the treatment of negative and depressive symptoms, and tolerability advantages such as the avoidance of weight gain. Essentially it rests with the treating clinician to employ a rational psychopharmacological approach towards the individual patient: there will be few circumstances in which amisulpride will not be a likely contender as a treatment choice.Keywords: amisulpride, negative symptoms, clozapine, depression 

  13. Differential Impact of Two Risk Communications on Antipsychotic Prescribing to People with Dementia in Scotland: Segmented Regression Time Series Analysis 2001–2011

    Science.gov (United States)

    Guthrie, Bruce; Clark, Stella A.; Reynish, Emma L.; McCowan, Colin; Morales, Daniel R.

    2013-01-01

    Background Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact. Methods Segmented regression time-series analysis 2001–2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing. Results The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI −6.6 to −5.2) and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs. Conclusions The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and

  14. Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects

    NARCIS (Netherlands)

    Girault, Elodie M.; Guigas, Bruno; Alkemade, Anneke; Foppen, Ewout; Ackermans, Mariëtte T.; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

    2014-01-01

    Atypical antipsychotic drugs such as olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these metabolic side-effects are unknown at the moment. In this study, we investigated the metabolic changes induced by a chronic

  15. Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects

    NARCIS (Netherlands)

    Girault, Elodie M; Guigas, Bruno; Alkemade, Anneke; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, A.

    Atypical antipsychotic drugs such as olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these metabolic side-effects are unknown at the moment. In this study, we investigated the metabolic changes induced by a chronic

  16. Olanzapine causes hypothermia, inactivity, a deranged feeding pattern and weight gain in female Wistar rats

    NARCIS (Netherlands)

    Evers, S. S.; Calcagnoli, F.; van Dijk, G.; Scheurink, A. J. W.

    2010-01-01

    Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine but also histamine muscarin and a adrenergic receptors In humans Olanzapine induces weight gain and increases the risk of type 2 diabetes The underlying mechanisms of Olanzapine-induced weight gain are unclear

  17. Risperidone versus typical antipsychotic medication for schizophrenia.

    Science.gov (United States)

    Hunter, R H; Joy, C B; Kennedy, E; Gilbody, S M; Song, F

    2003-01-01

    Risperidone is one of the 'new generation' antipsychotics. As well as its reputed tendency to cause fewer movement disorders than the older drugs such as chlorpromazine and haloperidol, it is claimed that risperidone may improve negative symptoms. To evaluate the effects of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. The original electronic searches of Biological Abstracts (1980-1997), Cochrane Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue 1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were updated with a new electronic search of the same databases in 2002. The search term used in the update was identical to that used in 1997. Any new studies or relevant references were added to the review. In addition, references of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were also contacted. All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for people with schizophrenia or other similar serious mental illnesses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Where possible, sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) were calculated on an intention-to-treat basis. In the short-term, risperidone was more likely to produce an improvement in the Positive and Negative Syndrome Scale (PANSS) when compared with haloperidol (n=2368, 9 RCTs, RR not 20% improved 0.72 CI 0.59 to 0.88 NNT 8). A similar, favourable outcome for risperidone was

  18. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  19. Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

    Science.gov (United States)

    Shin, Hyewon; Song, Jin-Ho

    2014-09-05

    Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: Do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

    Science.gov (United States)

    O’Callaghan, Matthew J; Bay-Richter, Cecilie; O’Tuathaigh, Colm MP; Heery, David M; Waddington, John L; Moran, Paula M

    2014-01-01

    Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner’s ‘two-headed’ model indicates that antipsychotics not only reverse LI disruption, ‘disrupted LI’, but also potentiate LI when low/absent in controls, ‘persistent’ LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2-/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1-/- and wild-type mice, indicating no such moderation in Drd1-/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis. PMID:25122042

  1. Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy

    Directory of Open Access Journals (Sweden)

    Keefe Richard SE

    2009-07-01

    Full Text Available Abstract Background Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs. Methods Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159, risperidone (n = 158, or haloperidol (n = 97. Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms. Results At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied. Conclusion Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and

  2. [Augmented antipsychotic therapy with pantogam active in patients with schizophrenia].

    Science.gov (United States)

    Medvedev, V E; Frolova, V I; Gushanskaya, E V; Ter-Israelyan, A U

    2015-01-01

    to study the efficacy of the GABA-ergic drug pantogam active (D-, L-gopantenic acid) in patients with schizophrenia treated with typical neuroleptics and to assess the rate of treatment response and tolerability of the drug. A sample consisted of 70 patients with schizophrenia stratified into main (n=35) and control (n=35) groups. All patients received one of typical antipsychotics (haloperidol, zuclopenthixol, promazine or perphenazine). Patients of the main group received in addition pantogam active in dose of 1200-1800 mg daily. The maximum allowed dose of 1800 mg daily was used in 62.9% of the patients. The long-term combined therapy with the addition of D-, L-gopantenic acid (pantogam activ) allowed to achieve clinical improvement earlier (on 8th week in the main group versus 16th week in the control group). The frequency and severity of secondary negative symptoms associated with antipsychotic therapy were decreased as well. The high efficacy and tolerability of the combined therapy allow to improve quality of life in patients with schizophrenia and their compliance to treatment as well as to reduce costs of medical care.

  3. Augmenting Clozapine With Sertindole

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Emborg, Charlotte; Gydesen, Susanne

    2012-01-01

    Clozapine augmentation with antipsychotic drugs is widely used despite sparse evidence supporting this strategy. Sertindole is a nonsedating atypical antipsychotic drug with low affinity for cholinergic receptors, which makes it potentially suitable for augmentation of clozapine. The study design...... glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude Inventory....... No increased adverse effects compared with placebo were found. Four patients randomized to sertindole experienced a significant worsening of psychosis, and 2 of them required psychiatric admission. Metabolic parameters were unchanged during the study, but augmentation of clozapine with sertindole...

  4. La valutazione economica del trattamento farmacologico con antipsicotici nella schizofrenia: una revisione sistematica della letteratura

    Directory of Open Access Journals (Sweden)

    R. Ravasio

    2005-03-01

    Full Text Available Schizophrenia is a chronic, severe, and disabling brain disease. Approximately 1 percent of the population develops schizophrenia during their lifetime. Available treatments can relieve many symptoms, but most people with schizophrenia continue to suffer some symptoms throughout their lives; it has been estimated that no more than one in five individuals recovers completely. The introduction of second-generation antipsychotics, also defined as atypicals, has increased the therapeutic options available for individuals with schizophrenia. Potential benefits of these agents include a more favourable profile in terms of positive and negative symptoms, less adverse effects and better cognitive functioning than first-generation antipsychotics. It is uncertain whether atypical antipsychotic agents, as prescribed in ordinary practice, are a cost-effective alternative to conventional agents. This study examined the financial and clinical implications of using atypical antipsychotics in the treatment of schizophrenia, considering both related costs and consequences. To elaborate the paper, we reviewed 8 economical studies regarding the comparison between atypical and typical antipsychotics, published in the years 1998-2004. In 5 studies atypical antipsychotics were cost-saving compared to typical, in 2 studies they were cost-neutral and in one study they resulted cost-effective. Consequently typical antipsychotics were cost-saving just in one study.

  5. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  6. Conspicuous by Their Absence: Studies Comparing and Combining Risperidone and Applied Behavior Analysis to Reduce Challenging Behavior in Children with Autism

    Science.gov (United States)

    Weeden, Marc; Ehrhardt, Kristal; Poling, Alan

    2009-01-01

    Both risperidone, an atypical antipsychotic drug, and function-based behavior-analytic interventions are popular and empirically validated treatments for reducing challenging behavior in children with autism. The kind of research that supports their effectiveness differs, however, and no published study has directly compared their effects or…

  7. [Pharmacotherapy in the treatment of borderline personality disorder].

    Science.gov (United States)

    Alliani, Daniela; Tarantelli, Silvia

    2009-01-01

    The aim of this study is to bring together the previous studies on pharmacotherapy of borderline disorder from the oldest to the recent ones, mainly focusing on atypical antipsychotic, whose success has been underlined in recent medical literature with peculiar reference to olanzapine. Since the '80 the pharmacotherapy in borderline personality disorder has been playing an increasing role in the interest of scientific community and in the medical practice as indicated by APA guidelines (2000). Nowadays the pharmacological approach, supported by some experimental outcomes, follow a so called "dimensional" standard. The targets of this standard drug approach are specific psychopathological "dimensions" of the disorder and related neurotransmitters' changes in particular linked to serotoninergic and dopaminergic systems, both supported by experimental outcomes. The psychopathological dimensions to which pharmacological approach is more suitable are: impulsiveness and emotional dysregulation. During the last past years, effectiveness of atypical antipsychotic drugs became of major interest in medical treatment of borderline disorder, mainly related to their action toward the serotoninergic and dopaminergic systems.

  8. Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study in patients with schizophrenia.

    Science.gov (United States)

    Biedermann, Falko; Fleischhacker, W Wolfgang; Kemmler, Georg; Ebenbichler, Christoph F; Lechleitner, Monika; Hofer, Alex

    2014-05-01

    Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

  9. Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study.

    Science.gov (United States)

    Rajkumar, Anto P; Horsdal, Henriette Thisted; Wimberley, Theresa; Cohen, Dan; Mors, Ole; Børglum, Anders D; Gasse, Christiane

    2017-07-01

    . Early detection and effective treatment of diabetes should be an integral part of multidisciplinary management of schizophrenia regardless of antipsychotic drug exposure.

  10. Atypical antipsychotics as add-on treatment in late-life depression

    Directory of Open Access Journals (Sweden)

    Cakir S

    2016-09-01

    Full Text Available Sibel Cakir,1 Zeynep Senkal2 1Department of Psychiatry, Mood Disorders, Geriatric Psychiatry Unit, Istanbul Medical School, Istanbul University, 2Department of Psychiatry, Marmara University, Istanbul, Turkey Background: Second-generation antipsychotics (SGAs have been used in the augmentation of treatment-resistant depression. However, little is known about their effectiveness, tolerability, and adverse events in the treatment of late-life depression, which were the aim of this study.Methods: The retrospective data of patients aged >65 years who had a major depressive episode with inadequate response to antidepressant treatment and had adjuvant SGA treatment were analyzed. The outcome measures were the number of the patients who continued to use SGAs in the fourth and twelfth weeks, adverse events, and changes in symptoms of depression. Results: Thirty-five patients were screened: 21 (60% had quetiapine, twelve (34.28% had aripiprazole, and two (5.71% had olanzapine adjuvant treatment. The mean age was 72.17±5.02 years, and 65.7% of the patients were women. The mean daily dose was 85.71±47.80 mg for quetiapine, 3.33±1.23 mg for aripiprazole, and 3.75±1.76 mg for olanzapine. The Geriatric Depression Scale scores of all patients were significantly decreased in the fourth week and were significant in the aripiprazole group (P=0.02. Of the 35 patients, 23 (65.7% patients discontinued the study within 12 weeks. The frequency of adverse events was similar in all SGAs, and the most common were sedation, dizziness, constipation, and orthostatic hypotension with quetiapine, and akathisia and headache because of aripiprazole. Conclusion: This study indicates that dropout ratio of patients with SGAs is high, and a subgroup of patients with late-life depression may benefit from SGAs. Effectiveness is significant in aripiprazole, and adverse events of SGAs were not serious but common in elderly patients. Keywords: treatment resistance, aripiprazole

  11. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agnoist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study - the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

    with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Materials and methods: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs...

  12. Il trattamento dei disturbi psicotici con olanzapina, risperidone e neurolettici tipici: una valutazione comparativa di costo/efficacia in una realtà psichiatrica locale

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    Egidio Filippelli

    2005-09-01

    Full Text Available BACKGROUND: Several clinical trials demonstrated that atypical antipsychotics are more effective but also more expensive (as drug cost compared with the typical neuroleptics by treating psychotic disorders. The present study aimed to evaluate this result using an observational approach which better reflects the real clinical practice. OBJECTIVE: To evaluate clinical effectiveness (including work and social functioning and overall direct costs in a group of patients affected by psychotic disorders (schizophrenia and bipolar and treated with typical and atypical (olanzapine and risperidone antipsychotics. METHODS: With a multicentre observational design - two years long - 89 patients (in charge by Psychiatric Centers of Regione Campania - Italy were assessed using CGI (Clinical Global Impression and GAF (Global Assessment of Functioning scales. Moreover economic data were collected with reference to pharmacological and non-pharmacological (hospitalization, medical/nurse visits, etc. resources consumption. The pharmacoeconomic analysis were conducted choosing the perspective of the local Psychiatric Services for costs attribution. RESULTS: Considering the treatment outcomes, the use of the atypical drugs provided better performances with reference to the patients quality of life. The results in terms of work and social functioning indicated an advantage in the olanzapine group of patients. Overall direct costs of treatment (drugs and healthcare resources didn’t generate significant differences among the groups of therapy despite the pharmacological cost evidentiated an economic advantage (p<0,05 in the typical group due to the cheaper cost of these drugs. The use of olanzapine was associated to a lower number of hospitalizations and showed a general reduction (- 16% of total treatment costs between 1st and 2nd year of observation. CONCLUSIONS: The lack of side effects, the improvement in work and social functioning, associated to a more efficient

  13. Crosstalk between insulin and dopamine signaling: A basis for the metabolic effects of antipsychotic drugs.

    Science.gov (United States)

    Nash, Abigail I

    2017-10-01

    In the setting of rising rates of obesity and metabolic syndrome, characterized in part by hyperinsulinemia, it is increasingly important to understand the mechanisms that contribute to insulin dysregulation. The higher risk for metabolic syndrome imparted by antipsychotic medication use highlights one such mechanism. Though there is great variation in the number and types of signaling pathways targeted by these medications, the one common mechanism of action is through dopamine. Dopamine's effects on insulin signaling begin at the level of insulin secretion from the pancreas and continue through the central nervous system. In a reciprocal fashion, insulin also affects dopamine signaling, with specific effects on dopamine reuptake from the synapse. This review probes the dopamine-insulin connection to provide a comprehensive examination of how antipsychotics may contribute towards insulin resistance. Published by Elsevier B.V.

  14. Can authorities appreciably enhance the prescribing of oral generic risperidone to conserve resources? Findings from across Europe and their implications.

    Science.gov (United States)

    Godman, Brian; Petzold, Max; Bennett, Kathleen; Bennie, Marion; Bucsics, Anna; Finlayson, Alexander E; Martin, Andrew; Persson, Marie; Piessnegger, Jutta; Raschi, Emanuel; Simoens, Steven; Zara, Corinne; Barbui, Corrado

    2014-06-13

    Generic atypical antipsychotic drugs offer health authorities opportunities for considerable savings. However, schizophrenia and bipolar disorders are complex diseases that require tailored treatments. Consequently, generally there have been limited demand-side measures by health authorities to encourage the preferential prescribing of generics. This is unlike the situation with hypertension, hypercholaesterolaemia or acid-related stomach disorders.The objectives of this study were to compare the effect of the limited demand-side measures in Western European countries and regions on the subsequent prescribing of risperidone following generics; to utilise the findings to provide future guidance to health authorities; and where possible, to investigate the utilisation of generic versus originator risperidone and the prices for generic risperidone. Principally, this was a segmented regression analysis of retrospective time-series data of the effect of the various initiatives in Belgium, Ireland, Scotland and Sweden following the introduction of generic risperidone. The study included patients prescribed at least one atypical antipsychotic drug up to 20 months before and up to 20 months after generic risperidone. In addition, retrospective observational studies were carried out in Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary care organisation (Bury Primary Care Trust (PCT)). There was a consistent steady reduction in risperidone as a percentage of total selected atypical antipsychotic utilisation following generics. A similar pattern was seen in Austria and Spain, with stable utilisation in one English PCT. However, there was considerable variation in the utilisation of generic risperidone, ranging from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the price of generic risperidone varied considerably. In Scotland, generic risperidone was only 16% of pre-patent loss prices versus 72% in Ireland. Consistent

  15. Schizophrenia, antipsychotics and risk of hip fracture

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Jensen, Signe O W; Nielsen, Jimmi

    2013-01-01

    In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co......-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture...... (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics...

  16. Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life: Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012

    Directory of Open Access Journals (Sweden)

    Yu-Xi Wang

    2015-01-01

    Conclusions: Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients′ and relatives′ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.

  17. Can melatonin prevent or improve metabolic side effects during antipsychotic treatments?

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    Porfirio MC

    2017-08-01

    Full Text Available Maria-Cristina Porfirio,1 Juliana Paula Gomes de Almeida,2 Maddalena Stornelli,1 Silvia Giovinazzo,1 Diane Purper-Ouakil,3 Gabriele Masi4 1Unit of Child Neurology and Psychiatry, “Tor Vergata” University of Rome, Italy; 2Unit of Child Neurology, Irmandade Santa Casa de Misericordia Hospital São Paulo, Brazil; 3Unit of Child and Adolescent Psychiatry, Saint Eloi Hospital, Montpellier, France; 4IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy Abstract: In the last two decades, second-generation antipsychotics (SGAs were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs can cause

  18. Molindone for schizophrenia and severe mental illness.

    Science.gov (United States)

    Bagnall, A; Fenton, M; Kleijnen, J; Lewis, R

    2007-01-24

    Antipsychotic therapy is the mainstay of treatment for people with schizophrenia. In recent years new or atypical antipsychotics have been introduced. These are less likely to produce movement disorders and raise serum prolactin. Researchers have suggested that molindone should be classified as an atypical antipsychotic. To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. For the original search we searched the following databases: Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999). We also searched pharmaceutical databases on the Dialog Corporation Datastar and Dialog and the references of all identified studies for further trials. Finally, we contacted the manufacturer of molindone and the authors of any relevant trials. For the update of this review, we searched The Cochrane Schizophrenia Group's Trials Register (August 2005). We included all randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses. We extracted data independently and analysed on an intention to treat basis calculating, for binary data, the fixed effect relative risk (RR), their 95% confidence intervals (CI), and the number needed to treat or harm (NNT or NNH). We excluded data if loss to follow up was greater than 50%. We included fourteen studies. Duration ranged from very short (10 days) studies of the intramuscular preparation, to trials lasting over three months. For measures of global assessment, available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics we found no evidence of a difference in effectiveness (doctors' 4 RCTs n=150

  19. Effect of GLP-1 Receptor Agonist Treatment on Body weight in Obese Antipsychotic-treated Patients with Schizophrenia

    DEFF Research Database (Denmark)

    Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V

    2017-01-01

    AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like obesity...... and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia. MATERIAL AND METHODS......: Antipsychotic-treated, obese, non-diabetic, schizophrenia spectrum patients were randomized to double-blinded adjunctive treatment with once-weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for three months. The primary outcome was body weight loss after treatment and repeated measures...

  20. Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients.

    Science.gov (United States)

    Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna; Mortensen, Henrik B; Søgaard, Birgitte; Holst, Jens J; Szecsi, Pal B; Lublin, Henrik

    2014-09-01

    Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice. ClinicalTrials.gov identifier NCT00627757. © Copyright 2014 Physicians Postgraduate Press, Inc.

  1. Attitudes toward antipsychotic treatment among patients with bipolar disorders and their clinicians: a systematic review

    Directory of Open Access Journals (Sweden)

    Sajatovic M

    2017-08-01

    may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder. Conclusion: Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted. Keywords: bipolar disorder, antipsychotics, systematic review, attitudes

  2. Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter; Lublin, H

    2010-01-01

    polypharmacy, socioeconomic status and functional level of patients. The intervention was aimed at psychiatric healthcare providers and consisted of 1 day of didactic lectures, six 3-h educational outreach visits and an electronic reminder during drug prescribing. RESULTS: Between-group use of antipsychotic...

  3. Fluvoxamine monotherapy for psychotic depression: the potential role of sigma-1 receptors

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    Hashimoto Kenji

    2009-12-01

    Full Text Available Abstract Background Psychotic depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI and an atypical antipsychotic or electroconvulsive therapy in treating psychotic depression. In some cases, the clinician or patient may prefer to avoid antipsychotic drugs altogether because of the risk of extrapyramidal side effects (EPS in patients with psychotic depression treated with these drugs. Methods We report five cases where fluvoxamine monotherapy was effective in the patients with psychotic depression. Results The scores on the Hamilton Depression (HAM-D scale and the Brief Psychiatric Rating Scale (BPRS in the five patients with psychotic depression were reduced after fluvoxamine monotherapy. Conclusion Doctors should consider fluvoxamine monotherapy as an alternative approach in treating psychotic depression because it avoids the risk of EPS from antipsychotic drugs.

  4. What is the role of sedating antidepressants, antipsychotics, and anticonvulsants in the management of insomnia?

    Science.gov (United States)

    McCall, Catherine; McCall, W Vaughn

    2012-10-01

    Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.

  5. Impact of Paliperidone Palmitate Versus Oral Atypical Antipsychotics on Health Care Resource Use and Costs in Veterans With Schizophrenia and Comorbid Substance Abuse.

    Science.gov (United States)

    Lefebvre, Patrick; Muser, Erik; Joshi, Kruti; DerSarkissian, Maral; Bhak, Rachel H; Duh, Mei Sheng; Shiner, Brian; Young-Xu, Yinong

    2017-07-01

    Almost half of all patients diagnosed with schizophrenia have a history of substance abuse (SA). However, data on treatment of schizophrenia with paliperidone palmitate (PP) among patients with comorbid SA are limited. The objective of this study was to compare all-cause and SA-related health care resource utilization and costs in veterans with schizophrenia and co-occurring SA who were treated with PP versus oral atypical antipsychotics (OAAs). Veterans Health Administration electronic health record data were used to conduct a retrospective longitudinal study in veterans with schizophrenia who initiated PP or OAA between January 1, 2010 and June 30, 2016, had ≥12 months of enrollment before treatment initiation (baseline), were diagnosed with SA, and had ≥1 Global Assessment of Functioning score during baseline. Differences in baseline characteristics were adjusted for using inverse probability of treatment weighting. Adjusted cost differences and incidence rate ratios (IRR) for the association between PP versus OAA and all-cause and SA-related health care costs and health care resource utilization in the 12 months after treatment initiation were estimated with corresponding 95% CIs using weighted linear and Poisson regression models, respectively. Of 6872 veterans in the study, 1684 (25%) and 5188 (75%) were treated with PP and OAA, respectively. After adjustment, PP was associated with fewer all-cause inpatient (IRR = 0.88; 95% CI, 0.85 to 0.90), mental health-related inpatient (IRR = 0.88; 95% CI, 0.85 to 0.91), and long-term care stays (IRR = 0.53; 95% CI, 0.44 to 0.64), but more frequent mental health intensive case management visits (IRR = 1.51; 95% CI, 1.49 to 1.53) compared with OAA (all P schizophrenia and comorbid SA. Thus, PP appears to be a valuable treatment option for patients in this subpopulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H MRS) study.

    Science.gov (United States)

    Szulc, Agata; Galińska, Beata; Tarasów, Eugeniusz; Kubas, Bozena; Dzienis, Wojciech; Konarzewska, Beata; Poplawska, Regina; Tomczak, Anna A; Czernikiewicz, Andrzej; Walecki, Jerzy

    2007-05-01

    NAA, marker of neurons integrity and viability, is one of the most important brain metabolites visible in 1H MRS. In most studies of schizophrenia, the decrease of NAA level was observed in the temporal, frontal lobes and in the thalamus. This finding was observed more often among chronic patients, what suggests the influence of disease duration or the effect of neuroleptic treatment. The aim of the present study was the comparison of NAA levels in brain of schizophrenic patients taking typical and atypical neuroleptics. We analyzed the NAA levels in selected brain areas in 58 schizophrenic patients and 21 healthy controls. 10 patients were treated with typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 - risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels of 2x2x2 cm were localized in the left frontal, left temporal lobe and left thalamus. There were no differences in NAA levels between patients on typical and atypical medications analyzed together and separately (olanzapine, clozapine and risperidone groups). We also did not find any differences between patients taking selected atypical neuroleptics and controls. The NAA level in the thalamus in the group of patients receiving typical antipsychotics was the lowest among all groups and differed significantly from healthy controls. The results of our study suggest that atypical neuroleptics may have favorable effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA level in patients taking typical medication may be caused by the progression of the disease or by the direct action of these drugs.

  7. Translational PKPD modeling in schizophrenia: linking receptor occupancy of antipsychotics to efficacy and safety

    NARCIS (Netherlands)

    Pilla Reddy, Venkatesh; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2012-01-01

    Objectives: To link the brain dopamine D2 receptor occupancy (D2RO) of antipsychotic drugs with clinical endpoints of efficacy and safety to assess the therapeutic window of D2RO. Methods: Pharmacokinetic-Pharmacodynamic (PK-PD) models were developed to predict the D2 receptor occupancy of

  8. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

    with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...

  9. Concomitant NSAID use during antipsychotic treatment and risk of 2-year relapse - a population-based study of 16,253 incident patients with schizophrenia

    DEFF Research Database (Denmark)

    Köhler, Karl Ole; Petersen, Liselotte; Benros, Michael Eriksen

    2016-01-01

    OBJECTIVE: Clinical trials have indicated antipsychotic effects of non-steroidal anti-inflammatory drugs (NSAIDs) among incident patients with schizophrenia. We aimed to study, in a population-based setting, whether concomitant use of NSAIDs or paracetamol, changed 2-year relapse risk...... for schizophrenia. METHODS: We identified all incident patients with schizophrenia in Denmark diagnosed 1996-2012 initiating antipsychotic treatment within the year after diagnosis. We calculated concomitant treatment intervals for antipsychotic and NSAID or paracetamol use. Hazard rate ratios (HRR) were estimated...... using Cox regression adjusted for important covariates. MAIN OUTCOME MEASURES: 2-year relapse, i.e. (re)-hospitalizations with schizophrenia. RESULTS: Among 16,235 incident patients with schizophrenia using antipsychotics, 1480 (9.1%) used NSAIDs and 767 (4.7%) paracetamol. Concomitant use of NSAIDs...

  10. Effects of Antipsychotics on Dentate Gyrus Stem Cell Proliferation and Survival in Animal Models: A Critical Update

    Directory of Open Access Journals (Sweden)

    Gerburg Keilhoff

    2012-01-01

    Full Text Available Schizophrenia is a complex psychiatric disorder. Although a number of different hypotheses have been developed to explain its aetiopathogenesis, we are far from understanding it. There is clinical and experimental evidence indicating that neurodevelopmental factors play a major role. Disturbances in neurodevelopment might result in alterations of neuroanatomy and neurochemistry, leading to the typical symptoms observed in schizophrenia. The present paper will critically address the neurodevelopmental models underlying schizophrenia by discussing the effects of typical and atypical antipsychotics in animal models. We will specifically discuss the vitamin D deficiency model, the poly I:C model, the ketamine model, and the postnatal ventral hippocampal lesion model, all of which reflect core neurodevelopmental issues underlying schizophrenia onset.

  11. Effect of second-generation antipsychotics on employment and productivity in individuals with schizophrenia: an economic perspective.

    Science.gov (United States)

    Percudani, Mauro; Barbui, Corrado; Tansella, Michele

    2004-01-01

    Schizophrenia is a serious mental illness that imposes a considerable burden not only on those who are ill, but also on their families, neighbours and the wider society. Costs associated with treating people with schizophrenia are those derived from the use of a wide range of services provided by public psychiatric facilities and/or by voluntary and private agencies. In addition, a large part of the economic impact of schizophrenia is related to the difficulties that patients encounter in finding and keeping paid employment. The introduction of second-generation antipsychotics (SGAs), also defined as atypicals, has increased the therapeutic options available for individuals with schizophrenia. Potential benefits of these agents include a more favourable profile in terms of positive and negative symptoms, less adverse effects and better cognitive functioning than first-generation antipsychotics (FGAs). As a consequence, SGAs might favourably affect the capacity, seriously impaired in schizophrenia, of finding and keeping paid employment. To date, only 13 published studies have investigated the effect of SGA agents on employment and work productivity. Clozapine was studied in eight studies, while both olanzapine and risperidone were studied in three. Clozapine emerged as the SGA with at least some effect on work status. However, all but one clozapine study enrolled only a few individuals and did not adopt an experimental design, making it very difficult to judge the validity and generalisability of findings. Taken together, studies found little benefit, in terms of employment and work productivity, for the use of SGAs compared with FGAs. The evidence available suggests that until data demonstrate a robust effect of newer agents on employment, it remains mandatory for mental health professionals to use the most effective drug treatment together with non-pharmacological interventions, such as vocational rehabilitative programmes nested into models of community

  12. [Eating disorders in psychiatric patients during treatment with second generation antipsychotics].

    Science.gov (United States)

    Vasilenko, L M; Gorobets, L N; Bulanov, V S; Litvinov, A V; Ivanova, G P; Tsarenko, M A; Polyakovskaya, T P

    2015-01-01

    To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMIobesity grade 2-3 in 38 patients (BMI>30 kg/m²). Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these we developed recommendations for management of patients treated with second generation antipsychotics.

  13. [Maintenance Treatment With Antipsychotics for Adult Patients Diagnosed With Schizophrenia].

    Science.gov (United States)

    Gómez-Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; de la Hoz Bradford, Ana María; Tamayo Martínez, Nathalie; García Valencia, Jenny; Jaramillo González, Luis Eduardo

    2014-01-01

    To determine the effectiveness and security of the antipsychotics available for the management of adult patients with schizophrenia in the maintenance phase. To develop recommendations of treatment for the maintenance phase of the disease. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. 18 studies were included to evaluate the effectiveness and / or safety of different antipsychotic drugs first and second generation. Overall, antipsychotics (AP) showed superiority over placebo in relapse rate over 12 months (RR 0.59 95% CI 0.42, 0.82) and hospitalization rate over 24 months of follow-up (RR 0.38 95% 0.27, 0.55); its use is associated with increased risk of treatment dropout (RR 0.53 95% CI 0.46, 0.61) and adverse events such as weight gain, dystonia, extrapyramidal symptoms and sedation. There was no difference in the outcome of re hospitalizations, comparisons on quality of life, negative symptoms or weight gain between AP first and second generation. Continuous or standard dose regimens appear to be superior to intermittent or low doses in reducing the risk of abandonment of treatment regimes. Adult patients diagnosed with schizophrenia should receive maintenance treatment with antipsychotics. The medication of choice will depend on the management of the acute phase, the patient's tolerance to it and the presentation of adverse events. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  14. Antipsychotic activity of aqueous ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model

    Directory of Open Access Journals (Sweden)

    Bindu nee Giri Jain

    2010-01-01

    Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO. The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD2 receptor binding in a dose dependent manner in treated mice compared to the control group.

  15. Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates.

    Directory of Open Access Journals (Sweden)

    Maibritt B Andersen

    Full Text Available Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R-6-(3-butylthio-1,2,5-thiadiazol-4-yl-1-azabicyclo[3.2.1]octane (BuTAC exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects of BuTAC in primates. To this end, we investigated the effects of BuTAC on d-amphetamine-induced behaviour in antipsychotic-naive Cebus paella monkeys. Possible adverse events of BuTAC, were evaluated in the same monkeys as well as in monkeys sensitized to antipsychotic-induced extrapyramidal side effects. The present data suggests that, the muscarinic receptor ligand BuTAC exhibits antipsychotic-like behaviour in primates. The behavioural data of BuTAC as well as the new biochemical data further substantiate the rationale for the use of muscarinic M1/M2/M4-preferring receptor agonists as novel pharmacological tools in the treatment of schizophrenia.

  16. Multiple Antipsychotic Medication Use in Autism Spectrum Disorder.

    Science.gov (United States)

    Wink, Logan K; Pedapati, Ernest V; Horn, Paul S; McDougle, Christopher J; Erickson, Craig A

    2017-02-01

    The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well

  17. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States.

    Science.gov (United States)

    Sun, Shawn X; Liu, Gordon G; Christensen, Dale B; Fu, Alex Z

    2007-10-01

    To review the literature addressing the economic outcomes of nonadherence in the treatment of schizophrenia, and to utilize the review results to provide an update on the economic impact of hospitalizations among schizophrenia patients related to antipsychotic nonadherence. A structured search of EMBASE, Ovid MEDLINE, PubMed and PsycINFO for years 1995-2007 was conducted to identify published English-language articles addressing the economic impact of antipsychotic nonadherence in schizophrenia. The following key words were used in the search: compliance, noncompliance, adherence, nonadherence, relapse, economic, cost, and schizophrenia. A bibliographic search of retrieved articles was performed to identify additional studies. For a study to be included, the date of publication had to be from 1/1/1995 to 6/1/2007, and the impact of nonadherence had to be measured in terms of direct healthcare costs or inpatient days. Subsequently, an estimate of incremental hospitalization costs related to antipsychotic non adherence was extrapolated at the US national level based on the reviewed studies (nonadherence rate and hospitalization rate) and the National Inpatient Sample of Healthcare Cost and Utilization Project (average daily hospitalization costs). Seven studies were identified and reviewed based on the study design, measurement of medication nonadherence, study setting, and cost outcome results. Despite the varied adherence measures across studies, all articles reviewed showed that antipsychotic nonadherence was related to an increase in hospitalization rate, hospital days or hospital costs. We also estimated that the national rehospitalization costs related to antipsychotic nonadherence was $1479 million, ranging from $1392 million to $1826 million in the US in 2005. The estimate of rehospitalization costs was restricted to schizophrenia patients from the Medicaid program. Additionally, the studies we reviewed did not capture the newer antipsychotic drugs

  18. Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian

    2017-01-01

    to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population...

  19. Atypical subtrochanteric and diaphyseal femoral fractures

    DEFF Research Database (Denmark)

    Shane, Elizabeth; Burr, David; Abrahamsen, Bo

    2014-01-01

    Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exp......Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients...... with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features...... a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant...

  20. Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia

    DEFF Research Database (Denmark)

    Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V

    2017-01-01

    and placebo groups experienced significant ( P  = .004), however similar ( P  = .98), weight losses of 2.24 ± 3.3 and 2.23 ± 4.4 kg, respectively, after 3 months of treatment. CONCLUSIONS: Treatment with exenatide once-weekly did not promote weight loss in obese, antipsychotic-treated patients......AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects...... such as obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia. MATERIAL...

  1. Use of Fixed Dose Combination (FDC) Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Metformin, or Psychotropic Drugs

    Science.gov (United States)

    McGettigan, Patricia; Roderick, Peter; Mahajan, Rushikesh; Kadam, Abhay; Pollock, Allyson M.

    2015-01-01

    Background In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC) drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO) in violation of rules, and considered that some ambiguity until 1 May 2002 about states’ powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin), depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti-psychotics). Methods and Findings This was an ecologic study with a time-trend analysis of FDC sales volumes (2007–2012) and a cross-sectional examination of 2011–2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval (“approved” and “unapproved”), their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011–2012) arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK), and United States of America (US) were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%) approved, 13 (81%) unapproved

  2. Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

    Science.gov (United States)

    Szkultecka-Dębek, Monika; Miernik, Katarzyna; Stelmachowski, Jarosław; Jakovljević, Miro; Jukić, Vlado; Aadamsoo, Kaire; Janno, Sven; Bitter, István; Tolna, Judit; Jarema, Marek; Jankovic, Slobodan; Pecenak, Jan; Vavrusova, Livia; Tavčar, Rok; Walczak, Jacek; Talbot, Darren; Augustyńska, Joanna

    2016-09-01

    The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries

  3. Metabolic effects of Olanzapine versus Iloperidone: A 24 weeks ...

    African Journals Online (AJOL)

    Atypical antipsychotics have become the mainstay of therapy for psychosis. Though extrapyramidal side effects have been reduced with atypical antipsychotics, yet there are increased concerns over metabolic effects. The present study is aimed to comparatively evaluate the metabolic profile of olanzapine and iloperidone ...

  4. Reporting sexual function disorders caused by antipsychotic drugs : is there a role for the community pharmacy?

    NARCIS (Netherlands)

    Rijcken, CAW; Dekens-Konter, JAM; Knegtering, H; de Jong-van den Berg, LTW

    2001-01-01

    Sexual function disorders are frequent adverse effects of antipsychotic use. These effects can lead to non-compliance to medication, which dramatically worsen the outcome of the psychotic disease. Detecting sexual dysfunction by the carers may be difficult, since feelings of embarrassment may occur

  5. Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity.

    Directory of Open Access Journals (Sweden)

    Hassan Nehme

    Full Text Available Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio, the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.

  6. New users of antipsychotic medication

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy. METHODS: Register-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare...... payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. RESULTS: The majority of new antipsychotic users...

  7. Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: a chart review study.

    Science.gov (United States)

    Adler, Benjamin A; Wink, Logan K; Early, Maureen; Shaffer, Rebecca; Minshawi, Noha; McDougle, Christopher J; Erickson, Craig A

    2015-01-01

    Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain. © The Author(s) 2014.

  8. Sex differences in concomitant medication with benzodiazepines or antidepressants in first-break schizophrenic patients treated with antipsychotic medication

    NARCIS (Netherlands)

    Rijcken, C.A.W.; Knegtering, H; Bruggeman, R; Tobi, H; de Jong-van den Berg, Lolkje Theodora Wilhelmina

    2005-01-01

    During a first episode of psychosis, treatment with antipsychotic drugs can improve both positive and negative symptoms. If sufficient amelioration does not occur, adding psychotropic comedication may result in a favorable outcome. To establish sex differences in psychotropic comedication use, we

  9. Schizophrenia as a disconnection syndrome. Studies with functional magnetic resonance imaging and structural equation modeling; Schizophrenie als Diskonnektionssyndrom. Studien mit funktioneller Magnetresonanztomographie und Strukturgleichungsmodellen

    Energy Technology Data Exchange (ETDEWEB)

    Schloesser, R. [Universitaet Jena, Psychiatrische Klinik (Germany); Universitaet Jena, Psychiatrische Klinik, Jena (Germany); Wagner, G.; Koehler, S.; Sauer, H. [Universitaet Jena, Psychiatrische Klinik (Germany)

    2005-02-01

    Aside from characteristic psychopathological symptoms, cognitive deficits are a core feature of schizophrenia. These deficits can only be addressed within the context of widespread functional interactions among different brain areas. To examine these interactions, structural equation modeling (SEM) was used for the analysis of fMRI datasets. In a series of studies, both in antipsychotic-treated and drug-free schizophrenic patients, a pattern of enhanced thalamocortical functional connectivity could be observed as an indicator for possible disruptions of frontostriatal thalamocortical circuitry. Moreover, drug-free patients and those receiving typical antipsychotic drugs were characterized by reduced interhemispheric corticocortical connectivity. This difference relative to normal controls was less in patients under atypical antipsychotic drugs. The results could be interpreted as a beneficial effect of atypical antipsychotic drugs on information processing in schizophrenic patients. The present findings are consistent with the model of schizophrenia as a disconnection syndrome and earlier concepts of ''cognitive dysmetria'' in schizophrenia. (orig.) [German] Neben der charakteristischen psychopathologischen Symptomatik stellen kognitive Defizite ein zentrales Merkmal der Schizophrenie dar. Diese Defizite koennen nur im Kontext miteinander interagierender Hirnareale verstanden werden. Zur Untersuchung dieser funktionellen Wechselbeziehungen wurden Strukturgleichungsmodelle (''structural equation modeling'', SEM) zur Auswertung von fMRT-Datensaetzen verwendet. In einer Untersuchungsreihe bei schizophrenen Patienten ergab sich sowohl bei antipsychotisch behandelten als auch bei unbehandelten Patienten ein Muster gesteigerter thalamokortikaler funktioneller Konnektivitaet als Hinweis auf eine moegliche Stoerung fronto-striato-thalamo-kortikaler Regelkreise. Unbehandelte Patienten und Patienten unter typischen Antipsychotika

  10. The expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders. Introduction: methods, commentary, and summary.

    Science.gov (United States)

    Kane, John M; Leucht, Stefan; Carpenter, Daniel; Docherty, John P

    2003-01-01

    (when available)were other high second line options for multi-episode patients. The expert's dosing recommendations agreed closely with the package inserts for the drugs, and their estimates of dose equivalence among the antipsychotics followed a linear pattern. The experts considered 3-6 weeks an adequate antipsychotic trial, but would wait a little longer (4-10 weeks) before making a major change in treatment regimen if there is a partial response. The experts recommended trying to improve response by increasing the dose of atypical and depot antipsychotics before switching to a different agent; there was less agreement about increasing the dose of conventional antipsychotics before switching, probably because of concern about side effects at higher doses. If it is decided to switch because of inadequate response, risperidone was the expert's first choice to switch to, no matter what drug was initially tried. Although there was some disparity in the expert's recommendations concerning how many agents to try before switching to clozapine, the expert's responses suggest that switching to clozapine should be Clozapine was also the antipsychotic of choice for patients with suicidal behavior. When switching oral antipsychotics,the experts considered cross-titration the preferred strategy. When switching to an injectable antipsychotic, the experts stressed the importance of continuing the oral antipsychotic until therapeutic levels of the injectable agent are achieved. The experts considered psychosocial interventions the first choice strategy for partially compliant patients, with pharmacologic interventions the first choice for patients with clear evidence of noncompliance. However, because it can be difficult to distinguish partially compliant from noncompliant patients, the editors recommended combining psychosocial and pharmacologic interventions to improve compliance whenever possible. When patients relapse because of compliance problems or if there is any doubt about

  11. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

    Science.gov (United States)

    Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

    2017-01-01

    Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk

  12. Mania associated with paliperidone treatment in schizophrenia: A case report

    Directory of Open Access Journals (Sweden)

    Süleyman Demir

    2015-09-01

    Full Text Available Paliperidone is an atypical antipsychotic drug used to treat schizophrenia. Paliperidone can cause some rare side effects during treatment. Despite many publications of mania and hypomania induced by antipsychotics, mania cases induced by paliperidone are few in the literature. In this case a schizophrenia patient showing symptoms of mania during usage of paliperidone with a dose of 9 mg/day in which the symptoms rapidly disappeared after discontinuation of paliperidone and initiation of aripiprazole was reported. Clinicians should be aware of that Paliperidone treatment may trigger mania symptoms. J Clin Exp Invest 2015; 6 (3: 321-323

  13. The availability of essential medicines for mental healthcare in Sofala, Mozambique

    Science.gov (United States)

    Wagenaar, Bradley H.; Stergachis, Andy; Rao, Deepa; Hoek, Roxanne; Cumbe, Vasco; Napúa, Manuel; Sherr, Kenneth

    2015-01-01

    Objective We assessed the availability of essential medicines for mental healthcare (MH) across levels of the public healthcare system to aid in future systems planning. Design Non-expired MH medications were assessed in 24 public health facilities and 13 district warehouses across Sofala Province, Mozambique, from July to August 2014. Medication categories included: antipsychotics, antidepressants, benzodiazepines, antiepileptics and mood stabilizers, and anticholinergics and antihistamines. Results Only 7 of 12 (58.3%) district warehouses, 11 of 24 (45.8%) of all health facilities, and 10 of 12 (83.3%) of facilities with trained MH staff had availability of at least one medication of each category. Thioridazine was the most commonly available antipsychotic across all facilities (9 of 24, 37.5%), while chlorpromazine and thioridazine were most common at facilities providing MH care (8 of 12, 66.7%). The atypical antipsychotic risperidone was not available at any facility or district warehouse. Amitriptyline was the most commonly available antidepressant (10 of 12 districts; 12 of 24 overall facilities; 9 or 12 MH facilities). Despite being on the national essential drug list, fluoxetine was only available at one quaternary-level facility and no district warehouses. Conclusions Essential psychotropic medicines are routinely unavailable at public health facilities. Current essential drug lists include six typical but no atypical antipsychotics, which is concerning given the side-effect profiles of typical antipsychotics. Ensuring consistent availability of at least one selective serotonin reuptake inhibitor should also be a priority, as they are essential for the treatment of individuals with underlying cardiovascular disease and/or suicidal ideation. Similar to successful task-sharing approaches used for HIV/AIDS, mid-level providers could be retrained and certified to prescribe and monitor first-line psychotropic regimens. PMID:26081970

  14. Oral health impacts of medications used to treat mental illness.

    Science.gov (United States)

    Cockburn, N; Pradhan, A; Taing, M W; Kisely, S; Ford, P J

    2017-12-01

    Many psychotropic medications affect oral health. This review identified oral side effects for antidepressant, antipsychotic, anticonvulsant, antianxiety and sedative drugs that are recommended in Australia for the management of common mental illnesses and provides recommendations to manage these side-effects. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat common mental health conditions. For each medication, the generic name, class, and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (eMIMs) and UpToDate databases. Meyler's Side Effect of Drugs Encyclopaedia was used to identify additional oral adverse reactions to these medications. Fifty-seven drugs were identified: 23 antidepressants, 22 antipsychotics or mood stabilisers, and 12 anxiolytic or sedative medications. Xerostomia (91%) the most commonly reported side effect among all classes of medications of the 28 identified symptoms. Other commonly reported adverse effects included dysguesia (65%) for antidepressants, and tardive dyskinesia (94%) or increased salivation (78%) for antipsychotic medications. While xerostomia has often been reported as a common adverse effect of psychotropic drugs, this review has identified additional side effects including dysguesia from antidepressants and tardive dyskinesia and increased salivation from antipsychotics. Clinicians should consider oral consequences of psychotropic medication in addition to other side-effects when prescribing. For antidepressants, this would mean choosing duloxetine, agomelatine and any of the serotonin re-uptake inhibitors except sertraline. In the case of antipsychotics and mood stabilisers, atypical agents have less oral side effects than older alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Prescription pattern and cost analysis of antipsychotics in a tertiary ...

    African Journals Online (AJOL)

    Our study revealed that the prescription patterns at the hospital studied were not in conformity with the WHO guidelines. Atypicals, are very expensive and unaffordable to the majority of patients in the study setting. This indicates the need for measures to reduce cost of newer psychotropic drugs, to increase their availability ...

  16. Propensity score estimation to address calendar time-specific channeling in comparative effectiveness research of second generation antipsychotics.

    Directory of Open Access Journals (Sweden)

    Stacie B Dusetzina

    Full Text Available Channeling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies.To demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time.Florida Medicaid data from 2001-2006.Retrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk.Increased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81-3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77-3.04.Changes in channeling over time was evident for several covariates but had limited impact on cardiovascular risk

  17. Managing cardiovascular disease risk in patients treated with antipsychotics: a multidisciplinary approach

    Directory of Open Access Journals (Sweden)

    Shulman M

    2014-10-01

    Full Text Available Matisyahu Shulman,1 Avraham Miller,2 Jason Misher,3 Aleksey Tentler4 1Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, NY, USA; 2The Ruth and Bruce Rappaport Faculty of Medicine, The Technion Israel Institute of Technology, Haifa, Israel; 3Department of Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA; 4Department of Internal Medicine, Rutgers New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA Background: The use of antipsychotic medication in the United States and throughout the world has greatly increased over the last fifteen years. These drugs have significant side effect burdens, many of them relating to cardiovascular health. Objective: To review the available evidence on the major cardiovascular issues that arise in patients taking antipsychotic medication. Method: A PubMed literature review was performed to identify recent meta-analyses, review articles, and large studies. Further articles were identified through cited papers and based on expert consultation when necessary. Results: Clinical guidance on the following adverse effects and antipsychotics was reviewed: electrocardiogram (ECG changes, (specifically, prolonged QT and risk of torsades de pointes, weight gain, dyslipidemia, metabolic syndrome, and myocarditis. Specific attention was paid to monitoring guidelines and treatment options in the event of adverse events, including dose change, medication switch, or adjuvant therapy. Keywords: schizophrenia, prolonged QT, increased mortality, weight gain, myocarditis

  18. Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Ricardo Alberto Moreno

    2004-10-01

    Full Text Available O transtorno bipolar é uma condição médica complexa e até o momento não há um tratamento único comprovadamente eficaz no controle de todos aspectos da doença. Foram revisadas a literatura disponível sobre o uso de anticonvulsivantes (valproato, carbamazepina, oxcarbazepina, lamotrigina, gabapentina, topiramato, clonazepam e antipsicóticos atípicos (clozapina, risperidona, olanzapina, quetiapina, ziprasidona e aripiprazole no tratamento agudo e profilático do transtorno bipolar. Existe um acúmulo de evidências acerca da eficácia do lítio na profilaxia e de ser melhor no tratamento da mania aguda do que nos episódios depressivos. Outros dados indicam que a carbamazepina e o valproato são eficazes na mania aguda. A lamotrigina parece reduzir ciclagem e ser eficaz em episódios depressivos. Baseado nas informações disponíveis, as evidências apontam a olanzapina como o antipsicótico atípico mais apropriado no tratamento de pacientes bipolares em mania, embora existam estudos sugerindo a eficácia da risperidona, aripiprazol e da clozapina. Resultados preliminares avaliando a eficácia de ziprasidona e quetiapina no transtorno bipolar ainda são bastante limitadas. Não há dados consistentes apoiando o uso profilático dos novos antipsicóticos.Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are

  19. Antipsychotics and the risk of sudden cardiac death

    NARCIS (Netherlands)

    Straus, S.M.J.M.; Bleumink, G.S.; Dieleman, J.P.; van der Lei, J.; 't Jong, G.W.; Kingma, J. Herre; Sturkenboom, M.C J M; Stricker, B.H C

    2004-01-01

    Background Antipsychotics have been associated with prolongation of the corrected QT interval and sudden cardiac death. Only a few epidemiological studies have investigated this association. We performed a case-control study to investigate the association between use of antipsychotics and sudden

  20. Patient perspectives on antipsychotic treatments and their association with clinical outcomes

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    2010-09-01

    Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

  1. The evolution of antipsychotic switch and polypharmacy in natural practice--a longitudinal perspective.

    Science.gov (United States)

    Tsutsumi, Chisa; Uchida, Hiroyuki; Suzuki, Takefumi; Watanabe, Koichiro; Takeuchi, Hiroyoshi; Nakajima, Shinichiro; Kimura, Yoshie; Tsutsumi, Yuichiro; Ishii, Koichi; Imasaka, Yasushi; Kapur, Shitij

    2011-08-01

    Most patients with schizophrenia first start with a single antipsychotic, and yet most finally end up 'switching' or using 'polypharmacy'. The objective of this study was to examine the evolution of antipsychotic switch and polypharmacy in the real-world from a longitudinal perspective. A systematic review of longitudinal antipsychotic prescriptions in 300 patients with schizophrenia (ICD-10) for up to 2 years after their first visit to one of the 4 participating psychiatric clinics in Tokyo, Japan between January, 2007 and June, 2008, was conducted. Reasons for prescription change were also examined. The evolution of switching and polypharmacy was studied, and prescribed doses were compared to suggested dose ranges by the Texas Medication Algorithm Project (TMAP). 208 patients started their antipsychotic treatment with monotherapy. 34.1% of the patients gave up monotherapy with an initial antipsychotic to move to antipsychotic switch (27.4%) and/or polypharmacy (17.8%) within 2 years. The main reason for antipsychotic switch was 'ineffectiveness'; interestingly, this happened despite the fact that the monotherapy dose was below the recommended range in 47.4% of the antipsychotic switch. In a subgroup of 100 patients who started as antipsychotic-free, 2-year prevalence rates of switching and antipsychotic polypharmacy were 27.0% and 18.0%, respectively, and polypharmacy was resorted to after a median of 1 antipsychotic had been tried for 84 days (median). These findings raise a concern that physicians may perform an antipsychotic switch without exploring the entire dose range and resort to antipsychotic polypharmacy without trying an adequate number of antipsychotics. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs).

    Science.gov (United States)

    Brugnoli, Roberto; Rapinesi, Chiara; Kotzalidis, Georgios D; Marcellusi, Andrea; Mennini, Francesco S; De Filippis, Sergio; Carrus, Dario; Ballerini, Andrea; Francomano, Antonio; Ducci, Giuseppe; Del Casale, Antonio; Girardi, Paolo

    2016-01-01

    Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. The

  3. Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

    Science.gov (United States)

    Newman-Tancredi, A; Rivet, J-M; Cussac, D; Touzard, M; Chaput, C; Marini, L; Millan, M J

    2003-09-01

    This study employed [(35)S]guanosine 5'- O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT(1A) receptors with those of reference agonists at postsynaptic 5-HT(1A) receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E(max), values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC(50)) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT(1A) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT(1A) receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding, consistent with partial agonist properties. In [(35)S]GTPgammaS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT(1A) receptors, was more potent in the septum (pEC(50) approximately 6.5) than in the dentate gyrus of the hippocampus (pEC(50) approximately 5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 microM) did not enhance [(35)S]GTPgammaS labelling in any structure, S16924 (10 micro M) modestly increased [(35)S]GTPgammaS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 microM)-stimulated [(35)S]GTPgammaS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G

  4. Treatment of Young People With Antipsychotic Medications in the United States.

    Science.gov (United States)

    Olfson, Mark; King, Marissa; Schoenbaum, Michael

    2015-09-01

    Despite concerns about rising treatment of young people with antipsychotic medications, little is known about trends and patterns of their use in the United States. To describe antipsychotic prescription patterns among young people in the United States, focusing on age and sex. A retrospective descriptive analysis of antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 (n = 765,829), 2008 (n = 858,216), and 2010 (n = 851,874), including a subset from calendar year 2009 with service claims data (n = 53,896). Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. The percentage of young people filling 1 or more antipsychotic prescriptions during the study year by sex and age group (younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years) was calculated. Among young people with antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined. The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%). Approximately 29.3% of

  5. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

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    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  6. Changes in antipsychotics and other psychotropic drugs during a 30-month lifestyle intervention among outpatients with schizophrenia

    DEFF Research Database (Denmark)

    Hojlund, Mikkel; Elliott, Anja Friis; Madsen, Nikolaj Juul

    2017-01-01

    BACKGROUND: Patients with schizophrenia have high risk of early death from diabetes and cardiovascular diseases, partly because of poor lifestyle and partly because of long-lasting exposure to antipsychotic treatment. AIMS: To investigate the influence of a lifestyle intervention program on chang...

  7. Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark.

    Science.gov (United States)

    Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian; Kørup, Alex Kappel; Søndergaard, Jens; Thygesen, Lau Caspar

    2017-10-01

    Earlier it has been found that female Seventh-day Adventists (SDA) and Baptists have an increased incidence of psychiatric affective disorders, in contrast to findings that religious practice is associated with better health. In this study, we examined whether the increase in incidence is due to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population between 1995 and 2010 in the Danish Prescription Register and compared the prevalence and incidence of use of antidepressants, sedatives and antipsychotics. The prevalence of antidepressant use by women was lower in 1998 but no different from that in controls in 2003 and 2008; the prevalence of antidepressant use by men was higher in both 1998 and 2008 than in the Danish population. The incidence of antidepressant use was lower for female members in 1996-2000, but no difference was observed in the other periods. The prevalence and incidence of use of sedatives and antipsychotics did not consistently differ from those of the general population. The prevalence and incidence of use of antidepressants, sedatives and antipsychotics by female SDA and Baptists were not consistently lower than in the general Danish population. Our findings hence do not explain the increased incidence of psychiatric disorders among female members of these Danish religious societies.

  8. Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter type-1 inhibitor Org-24461 and risperidone.

    Science.gov (United States)

    Nagy, Katalin; Marko, Bernadett; Zsilla, Gabriella; Matyus, Peter; Pallagi, Katalin; Szabo, Geza; Juranyi, Zsolt; Barkoczy, Jozsef; Levay, Gyorgy; Harsing, Laszlo G

    2010-12-01

    The most dominant hypotheses for the pathogenesis of schizophrenia have focused primarily upon hyperfunctional dopaminergic and hypofunctional glutamatergic neurotransmission in the central nervous system. The therapeutic efficacy of all atypical antipsychotics is explained in part by antagonism of the dopaminergic neurotransmission, mainly by blockade of D(2) dopamine receptors. N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia can be reversed by glycine transporter type-1 (GlyT-1) inhibitors, which regulate glycine concentrations at the vicinity of NMDA receptors. Combined drug administration with D(2) dopamine receptor blockade and activation of hypofunctional NMDA receptors may be needed for a more effective treatment of positive and negative symptoms and the accompanied cognitive deficit in schizophrenia. To investigate this type of combined drug administration, rats were treated with the atypical antipsychotic risperidone together with the GlyT-1 inhibitor Org-24461. Brain microdialysis was applied in the striatum of conscious rats and determinations of extracellular dopamine, DOPAC, HVA, glycine, glutamate, and serine concentrations were carried out using HPLC/electrochemistry. Risperidone increased extracellular concentrations of dopamine but failed to influence those of glycine or glutamate measured in microdialysis samples. Org-24461 injection reduced extracellular dopamine concentrations and elevated extracellular glycine levels but the concentrations of serine and glutamate were not changed. When risperidone and Org-24461 were added in combination, a decrease in extracellular dopamine concentrations was accompanied with sustained elevation of extracellular glycine levels. Interestingly, the extracellular concentrations of glutamate were also enhanced. Our data indicate that coadministration of an antipsychotic with a GlyT-1 inhibitor may normalize hypofunctional NMDA receptor-mediated glutamatergic neurotransmission with reduced

  9. Effect of olanzapine treatment on INR of a patient receiving warfarin therapy

    Directory of Open Access Journals (Sweden)

    Derya Arslan

    2016-06-01

    Full Text Available Olanzapine is an atypical antipsychotic drug, commonly used in the management of psychotic symptoms in patients with schizoprenia and bipolar affective disorder. Deep venous thrombosis is a manifestation of venous thromboembolism. It is very well known that use of antipsychotic drugs increase the risk of thrombosis in a patient with schizophrenia. It has been reported in many studies the effects of olanzapine on thrombosis but there isn't any report about the effect of olanzapine on international normalized ratio (INR. in the medical literature. In this paper, a patient with schizophrenia and also family history of deep venous thrombosis who emerged deep venous thrombosis after being started on olanzapine treatment and effect of olanzapine treatment on INR has been reported. [Cukurova Med J 2016; 41(2.000: 370-373

  10. Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

  11. Cost-effectiveness Analysis of Antipsychotic Combination Therapy in Schizophrenia Inpatients

    Directory of Open Access Journals (Sweden)

    Rizky Abdulah

    2017-03-01

    Full Text Available Schizophrenia is one of mental disorders with high cost and lifetime morbidity risk. Hence, it is necessary to analyze the cost-effectiveness of various combinations of antipsychotics. The aim of this study was to analyze the most cost-effective group of antipsychotic combinations in schizophrenia inpatients in West Java Psychiatric Hospital during 2012–2013. Data were collected retrospectively from medical record of patients who used antipsychotics clozapine-haloperidol or clozapine-risperidone therapy. Direct medical costs were obtained from antipsychotics costs, costs of medical treatment, medical expenses, hospitalization costs, and administrative costs. The results showed that the average cost-effectiveness ratio of antipsychotic clozapine-haloperidol was Rp126.898/day and Rp132.781/day for the combination of clozapine-haloperidol and clozapine-risperidone, respectively. Considering length of stay as the therapy effectiveness, it can be concluded that the combination of clozapine-haloperidol is more cost-effective than clozapine-risperidone.

  12. Neurological Adverse Effects of Antipsychotics in Children and Adolescents.

    Science.gov (United States)

    Garcia-Amador, Margarita; Merchán-Naranjo, Jessica; Tapia, Cecilia; Moreno, Carmen; Castro-Fornieles, Josefina; Baeza, Inmaculada; de la Serna, Elena; Alda, José A; Muñoz, Daniel; Andrés Nestares, Patricia; Cantarero, Carmen Martínez; Arango, Celso

    2015-12-01

    The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and

  13. Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Young Kyoung Sa

    2013-03-01

    Full Text Available Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS. However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA. In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

  14. [Psychoactive drugs and costs in the Madrid III (Valdemoro) prison].

    Science.gov (United States)

    Algora-Donoso, I; Varela-González, O

    2008-01-01

    Annual pharmaceutical expenditures in prisons increases dramatically and the rising costs of psychoactive drugs have especially contributed to this. These drugs are often prescribed in order to find therapeutic uses in the field of personality disorders, addictions, and dysfunctional behaviours that are not included in the authorized indications (compassionate use). This study has enabled a detailed description of the use of psychoactive drugs at the Madrid III prison, a centre with one of the lowest levels of pharmaceutical expenditure in this autonomous community. During a two-week period, all prescriptions of psychoactive drugs were collected and registered along with data of several possible conditioning factors. 20.5% of the population was receiving some kind of psychoactive drug; 76% of those inmates undergoing treatment were receiving one or two substances; 65% were taking anxiolytics, 38% antidepressants and 27% antipsychotics. The total amount of psychoactive drugs consumed was 9,840 defined daily doses, 46% of which were anxiolytics, 17% antidepressants and 14% antipsychotics. The total cost of the fortnight's treatment was euros 5,379 with a saving of euro 611 due to requesting and selecting offers carried out by the pharmacist. 72% of the costs were spent on anti-psychotics and the newer psychoactive drugs, representing 66% of the prescriptions, accounted for 98% of expenditure. The prescriber was one of the key influential factors over the amount, type and cost of the treatments. There are signs that compassionate use of current antipsychotics and antiepileptics, and newer antidepressants are a main cause of the dramatic increase in the costs, with cost-efficiency not always clearly demonstrated. These results are not an isolated fact restricted only to prisons, as demonstrated by consumption data published by the National Health System in the same year.

  15. Biological treatment of acute agitation or aggression with schizophrenia or bipolar disorder in the inpatient setting.

    Science.gov (United States)

    Correll, Christoph U; Yu, Xin; Xiang, Yutao; Kane, John M; Masand, Prakash

    2017-05-01

    Schizophrenia and bipolar disorders are chronic illnesses that commonly present with symptoms of acute agitation and aggression. These symptoms must be managed rapidly to prevent potential harm to the patient and others, including their caregivers, peers, and health care workers. A number of treatment options are available to clinicians to manage acute agitation and aggression, including non-pharmacologic behavioral and environmental de-escalation strategies, as well as biological treatment options such as pharmacologic agents and electroconvulsive therapy. We summarize the available biological treatment options for patients with schizophrenia or bipolar disorder presenting with acute agitation or aggression in the inpatient setting, focusing on antipsychotics. The following searches were used in PubMed to obtain the most relevant advances in treating schizophrenia or bipolar disorder with acute agitation and aggression: (agitation, agitated, aggression, aggressive, hostile, hostility, violent, or violence) and (schizophr*, psychosis, psychot*, psychos*, mania, manic, or bipolar) and (*pharmacologic, antipsychotic*, neuroleptic*, antiepileptic*, anti-seizure*, mood stabilizer*, lithium, benzodiazepine*, beta blocker, beta-blocker, alpha2, alpha-2, *histamine*, electroconvulsive, ECT, shock, or transcranial). Individual searches were performed for each drug class. The studies were limited to peer-reviewed, English-language, and human studies. Most were placebo-controlled randomized controlled trials (RCTs) or meta-analyses. Among pharmacologic agents, antipsychotics, benzodiazepines, anticonvulsants, and lithium have been studied in randomized trials. Some typical and, more recently, atypical antipsychotics are available as both oral and short-acting intramuscular (IM) formulations, with 1 typical antipsychotic also available as an inhalable formulation. Among the pharmacologic agents studied in RCTs, atypical antipsychotics have the best evidence to support

  16. Maintenance Electroconvulsive Therapy in a Patient with Treatment-Resistant Paranoid Schizophrenia and Comorbid Epilepsy

    Directory of Open Access Journals (Sweden)

    Beppe Micallef-Trigona

    2012-01-01

    Full Text Available The treatment of choice for acute schizophrenia is antipsychotic drug treatment and electroconvulsive therapy (ECT and should only be considered as an option for treatment-resistant schizophrenia, where treatment with clozapine has already proven ineffective or intolerable. The use of ECT as a maintenance treatment for patients with schizophrenia and comorbid epilepsy is uncommon as scant evidence exists to support this. We describe a patient with a serious case of paranoid schizophrenia and comorbid epilepsy who had not responded to typical and atypical antipsychotic medication, but responded remarkably to acute ECT and required maintenance ECT to sustain a positive therapeutic response.

  17. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE....... Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829....... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...

  18. Drug: D07623 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 01942 ... Iminobenzyl antipsychotic Chemical group: DG01312 ... Tricyclic antidepressant, Iminodibenzyl derivativ... D07623 Drug Carpipramine (INN) ... C28H38N4O D07623.gif ... Neuropsychiatric agent ... DG

  19. Atypical femoral fractures related to bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Tarun Pankaj Jain

    2012-01-01

    Full Text Available Bisphosphonates (BP are a commonly prescribed class of drugs for the prevention of osteoporosis-related fractures. Paradoxically, however, they have recently been linked to atypical fractures in the shaft of the femur. Since many physicians including radiologists, are not aware of this entity, the incidence is likely underreported. These fractures usually occur in the sub-trochanteric region of the femur in the setting of low-energy trauma. It starts as a fracture line involving the lateral cortex and then progresses medially to give rise to a complete fracture. The fracture line is usually transverse, and there is a medial spike associated with a complete fracture. These fractures can be bilateral. Awareness of these atypical fractures and their radiological appearance should enable their early and accurate detection and thus lead to specific treatment.

  20. Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum.

    Science.gov (United States)

    Garver, D L; Holcomb, J A; Christensen, J D

    2000-12-01

    Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good-prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent

  1. Patient compliance with drug therapy in schizophrenia. Economic and clinical issues.

    Science.gov (United States)

    Lindström, E; Bingefors, K

    2000-08-01

    The effectiveness of drug treatment in clinical practice is considerably lower than the efficacy shown in controlled studies. The lower effectiveness in practice presumably leads to lower cost effectiveness of drug treatment in real-life situations compared with that demonstrated by studies based on results from controlled trials. Improved cost effectiveness in routine clinical practice would be a significant advantage in the treatment of schizophrenia, one of the most costly diseases in society. The aetiology of schizophrenia is unknown, and there is no cure. The main aims of therapy with antipsychotic medication include the effective relief of symptoms without the introduction of adverse effects or serious adverse events, improved quality of life, cost effectiveness and a positive long term outcome. The older classical antipsychotic drugs do not always meet these requirements because of their well-known limitations, such as a lack of response in a subgroup of individuals with schizophrenia and intolerable adverse effects. There has long been a need for new antipsychotics that can ameliorate more symptoms and have no or few adverse effects. Some of the recently introduced antipsychotics have been shown to be more effective in certain clinical situations and to have a more favourable adverse effect profile than the classical antipsychotics. A major factor contributing to the lower effectiveness of drug treatment is noncompliance, which may be very high in schizophrenia. There are several factors influencing compliance, including drug type and formulation, patient, disease status, physician, health care system, community care and family. There have been very few studies of compliance improvement strategies in schizophrenia or, indeed, in medicine in general. Current methods are relatively complex and there are differing opinions on their effectiveness. There are several ways to increase compliance in schizophrenia--the evidence is strongest for psychoeducative

  2. Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Laura R. Magni

    2017-03-01

    Full Text Available Objective: To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program on weight gain compared with a treatment-as-usual (TAU approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI variation and clinical variables. Method: Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59 and control (n=26. The Superwellness Program (experimental group consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks, and after 6 months. Results: BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021. Duration of illness moderated the effect of treatment on BMI (p = 0.026. No significant (p = 0.499 effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024 reduction in metabolic risk by reducing BMI. Conclusion: A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

  3. [Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

    Science.gov (United States)

    Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

    2016-01-01

    Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  4. Patient satisfaction with psychotropic drugs: sensitivity to change and relationship to clinical status, quality-of-life, compliance and effectiveness of treatment. Results from a nation-wide 6-month prospective study.

    Science.gov (United States)

    Gasquet, Isabelle; Tcherny-Lessenot, Stéphanie; Lépine, Jean-Pierre; Falissard, Bruno

    2006-12-01

    To see if patient satisfaction with psychotropics (PSP) could be used as a patient-oriented outcome variable in the evaluation of PSP drugs in clinical epidemiological studies, relationships between PSP, clinical status, QoL, compliance and the type of antipsychotic were analyzed. Elements of validation of PSP were also assessed. In a 6-month prospective study, 933 schizophrenic outpatients with initiation or change to their antipsychotic treatment were enrolled. Psychiatrists completed five CGI-SCH scales (positive, negative, cognitive, depressive and global), hospitalization, compliance, and prescription variables. Patients completed PSP, EuroQoL scales, sexual function and compliance variables. A satisfactory structural equation model was obtained showing significant relationships PSP/compliance (coef.=0.16), QoL/PSP (coef.=0.37), clinical status/QoL (coef.=0.61), clinical status/compliance (coef.=0.09). Patients receiving olanzapine were more satisfied than patients receiving other atypicals (coef.=012) and had better clinical status than patients treated with typicals (coef.=0.08). Evolution of PSP was related to clinical status, QoL, and continuation of treatment (all Pmeasure was not sufficiently sensitive to change. Multi-item questionnaires evaluating different dimensions are needed.

  5. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  6. In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug.

    Directory of Open Access Journals (Sweden)

    Xi-Nan Shi

    Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg. Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history

  7. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    Science.gov (United States)

    Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

    2017-01-01

    Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

  8. Efeitos adversos metabólicos de antipsicóticos e estabilizadores de humor Metabolic side effects of antipsychotics and mood stabilizers

    Directory of Open Access Journals (Sweden)

    Paulo José Ribeiro Teixeira

    2006-08-01

    Full Text Available INTRODUÇÃO: Um aumento na incidência de obesidade e diabetes melito entre pacientes psiquiátricos foi observado ainda na década de 60, como resultado indesejável do uso de antipsicóticos. Nos anos 80 e 90, a reabilitação da clozapina, a síntese dos demais antipsicóticos atípicos e a disseminação do uso do lítio e do ácido valpróico chamaram novamente a atenção para os efeitos metabólicos desses medicamentos. Este estudo tem por objetivo revisar a literatura médica a respeito dos efeitos adversos metabólicos associados ao uso de antipsicóticos e estabilizadores de humor. MÉTODO: Foi realizada uma extensa pesquisa nas bases de dados MEDLINE e LILACS até outubro de 2005. CONCLUSÃO: Os efeitos adversos metabólicos permanecem como problemas importantes da psicofarmacologia. Ganho de peso clinicamente relevante ocorre com freqüência em pacientes em uso de antipsicóticos e estabilizadores de humor, principalmente naqueles em uso de clozapina, olanzapina, lítio e ácido valpróico. A clozapina e a olanzapina associam-se também a uma maior incidência de diabetes melito e dislipidemias, seja devido ao ganho de peso, seja por ação deletéria direta sobre o metabolismo da glicose. A incidência de obesidade e outros distúrbios metabólicos é menor com a risperidona, se comparada à olanzapina ou à clozapina. Carbamazepina associa-se a menor ganho de peso, se comparada ao lítio ou ao ácido valpróico. Drogas como o haloperidol, a ziprasidona, o aripiprazol e a lamotrigina não estão associadas a ganho importante de peso ou a maior incidência de diabetes melito e são alternativas para pacientes mais propensos a desenvolver tais efeitos adversos.BACKGROUND: An increase in the incidence of obesity and diabetes mellitus in psychiatric patients using antipsychotic drugs was observed as early as the 1960's. In the 1980's and 1990's, rehabilitation of clozapine, synthesis of other atypical antipsychotics, and spread of the

  9. Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response-a prospective open-label study.

    Science.gov (United States)

    Hashimoto, Naoki; Toyomaki, Atsuhito; Honda, Minoru; Miyano, Satoru; Nitta, Nobuyuki; Sawayama, Hiroyuki; Sugawara, Yasufumi; Uemura, Keiichi; Tsukamoto, Noriko; Koyama, Tsukasa; Kusumi, Ichiro

    2015-01-01

    While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the Schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and

  10. The ticking of the epigenetic clock: antipsychotic drugs in old age

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    Adonis Sfera

    2016-08-01

    Full Text Available AbstractBackground: Exposed to antipsychotic drugs (APDs, older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE, including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs, however they seldom progresses to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear.CNS small vessel disease (SVD is a well-known age-related risk factor for strokes, dementia and sudden death, which may constitute the initial CVAE-predisposing pathology. We therefore propose a two strike CVAE paradigm in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities (WMH may be directly proportional with the CVAE risk.To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4. Since microRNA-29 has shown efficacy against the same malignancies, and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 up-regulation, which in turn facilitates the development of SVD. Aim: to assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.Method: we conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity, and may be relevant for CVAE

  11. The effect of federal and state off-label marketing investigations on drug prescribing: The case of olanzapine.

    Science.gov (United States)

    Wang, Bo; Studdert, David M; Sarpatwari, Ameet; Franklin, Jessica M; Landon, Joan; Kesselheim, Aaron S

    2017-01-01

    In the past decade, the federal government has frequently investigated and prosecuted pharmaceutical manufacturers for illegal promotion of drugs for indications not approved by the Food and Drug Administration (FDA) ("off-label" uses). State governments can choose to coordinate with the federal investigation, or pursue their own independent state investigations. One of the largest-ever off-label prosecutions relates to the atypical antipsychotic drug olanzapine (Zyprexa). In a series of settlements between 2008 and 2010, Eli Lilly paid $1.4 billion to the federal government and over $290 million to state governments. We examined the effect of these settlements on off-label prescribing of this medication, taking advantage of geographical differences in states' involvement in the investigations and the timing of the settlements. However, we did not find a reduction in off-label prescribing; rather, there were no prescribing changes among states that joined the federal investigation, those that pursued independent state investigations, and states that pursued no investigations at all. Since the settlements of state investigations of off-label prescribing do not appear to significantly impact prescribing rates, policymakers should consider alternate ways of reducing the prevalence of non-evidence-based off-label use to complement their ongoing investigations.

  12. [Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

    Science.gov (United States)

    Jaramillo González, Luis Eduardo; Gómez Restrepo, Carlos; García Valencia, Jenny; de la Hoz Bradford, Ana María; Ávila-Guerra, Mauricio; Bohórquez Peñaranda, Adriana

    2014-01-01

    To determine the indications of long-acting antipsychotic injection and what its effectiveness and safety in adult patients with schizophrenia during the treatment maintenance phase. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The literature review shows that the evidence has moderate to low quality. 8 articles were used. The risk of relapse was lower with depot risperidone and paliperidone palmitate when compared with placebo. For the risk of hospitalizations comparing depot antipsychotics (APD) versus oral AP, the result is inconclusive. Globally the second-generation APD had a lower risk of discontinuation when compared with placebo. The second generation AP had higher risk of extrapyramidal syndromes than placebo, as in the use of antiparkinsonian. The comparison of second-generation AP injections versus placebo showed an increased risk of early weight gain. The use of depot antipsychotics in the maintenance phase of adult patients diagnosed with schizophrenia is recommended if there is no adherence to oral antipsychotics as the patient's preference. It is not recommended depot antipsychotics in the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  13. Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology survey

    Directory of Open Access Journals (Sweden)

    Russo Federico

    2007-11-01

    Full Text Available Abstract Background The PERSEO study (psychiatric emergency study and epidemiology is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management. The aims of this paper are: (i to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46% showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%, than in aggression toward other people (20%. A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%, followed by depression (16% and personality disorders (14%, and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge, while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge and depression (41 vs 32% during stay and 44 vs 25% at discharge. Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%. Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self

  14. Use of second-generation antipsychotic agents for sleep and sedation: a provider survey.

    Science.gov (United States)

    Hermes, Eric D A; Sernyak, Michael; Rosenheck, Robert

    2013-04-01

    Anecdotal evidence suggests that second-generation antipsychotic agents are increasingly used to treat sleep problems. This study sought to quantify the proportion of new prescriptions for second-generation antipsychotic agents started for sleep/sedation and the correlates of such use. A cross-sectional survey of provider decision making at the time second-generation antipsychotic agents were prescribed, documenting the reasons for the medication, patient demographics, psychiatric and medical diagnoses, patient health characteristics, and provider background. A single Veterans Affairs Medical Center over a 20-month period. Prescribers of second-generation antipsychotic agents. N/A. Seven hundred seven (32.2%) of 2,613 surveys indicated sleep/sedation was at least one reason for using a second-generation anti-psychotic agent, whereas for 266 (12.1%) it was the only reason. Quetiapine was most frequently prescribed overall as well as for sleep/sedation (47.0% and 73.6% respectively). Second-generation antipsychotic agent use for sleep/sedation was unrelated to sociodemographic characteristics, least likely in patients with schizophrenia or bipolar disorder, and most likely as a newly started second-generation antipsychotic agent. Sleep/sedation is a common reason given for new prescriptions of second-generation antipsychotic agents. Quetiapine is most frequently used for this purpose. A greater understanding of why providers use second-generation antipsychotic agents rather than safer and less costly alternatives for sleep problems may advance the development of interventions to reduce adverse effects.

  15. Gamma-aminobutyric acid agonists for antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    Alabed, Samer; Latifeh, Youssef; Mohammad, Husam Aldeen; Bergman, Hanna

    2018-04-17

    Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. 1. Primary objectiveThe primary objective was to determine whether using non-benzodiazepine GABA agonist drugs for at least six weeks was clinically effective for the treatment of antipsychotic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.2. Secondary objectivesThe secondary objectives were as follows.To examine whether any improvement occurred with short periods of intervention (less than six weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.To examine whether there was a differential effect between the various compounds.To test the hypothesis that GABA agonist drugs are most effective for a younger age group (less than 40 years old). We searched the Cochrane Schizophrenia Group Trials Register (last searched April 2017), inspected references of all identified studies for further trials, and, when necessary, contacted authors of trials for additional information. We included randomised controlled trials of non-benzodiazepine GABA agonist drugs in people with antipsychotic-induced TD and schizophrenia or other chronic mental illness. Two review authors independently selected and critically appraised studies, extracted and analysed data on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous data we calculated mean differences (MD). We assumed that people who left early had no improvement. We contacted investigators to obtain missing information. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We included 11 studies that randomised 343 people. Overall, the risk of bias

  16. Metabolic Syndrome in Schizophrenia: A Non‑systematic Review

    Directory of Open Access Journals (Sweden)

    Marta Nascimento

    2012-12-01

    Full Text Available Background: The link between mental illness and metabolic disturbances has been recognized since the beginning of the last century. The debate concerning medical morbidity in schizophrenia intensified during the last twenty years, especially after the introduction of atypical antipsychotics. Aims: To highlight some features of the metabolic syndrome in this population, specifically epidemiological data, underlying mechanisms and antipsychotic therapy. Methods: Non‑systematic review of literature. Results and Conclusions: Despite the different criteria used for the definition of metabolic syndrome, it is clear today that the schizophrenic population has the highest rate of metabolic syndrome. Additionally, the prevalence of the metabolic syndrome in this population demonstrates a geographical distribution similar to the general population. Although it hasn’t been recognized for years, schizophrenic patients’ vulnerability to develop metabolic disturbances isn’t entirely related to antipsychotic therapy. Actually, it results from an interaction of multiple factors, including hereditary, genetic, biochemical and environmental ones (which include antipsychotic therapy. Moreover, they are not exclusively explained by weight gain. Metabolic disturbances are one of the main concerns related to general psychopharmacology. The differences between typical and atypical antipsychotics in terms of metabolic syndrome are not completely established. However, clozapine and olanzapine are recognized to have the worst metabolic profile, amongst all atypical antipsychotics.

  17. Metabolic Syndrome in Schizophrenia: A Non‑systematic Review

    Directory of Open Access Journals (Sweden)

    Marta Nascimento

    2013-11-01

    Full Text Available Background: The link between mental illness and metabolic disturbances has been recognized since the beginning of the last century. The debate concerning medical morbidity in schizophrenia intensified during the last twenty years, especially after the introduction of atypical antipsychotics. Aims: To highlight some features of the metabolic syndrome in this population, specifically epidemiological data, underlying mechanisms and antipsychotic therapy. Methods: Non‑systematic review of literature. Results and Conclusions: Despite the different criteria used for the definition of metabolic syndrome, it is clear today that the schizophrenic population has the highest rate of metabolic syndrome. Additionally, the prevalence of the metabolic syndrome in this population demonstrates a geographical distribution similar to the general population. Although it hasn’t been recognized for years, schizophrenic patients’ vulnerability to develop metabolic disturbances isn’t entirely related to antipsychotic therapy. Actually, it results from an interaction of multiple factors, including hereditary, genetic, biochemical and environmental ones (which include antipsychotic therapy. Moreover, they are not exclusively explained by weight gain. Metabolic disturbances are one of the main concerns related to general psychopharmacology. The differences between typical and atypical antipsychotics in terms of metabolic syndrome are not completely established. However, clozapine and olanzapine are recognized to have the worst metabolic profile, amongst all atypical antipsychotics.

  18. Comparison of patients undergoing switching versus augmentation of antipsychotic medications during treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2012-03-01

    Full Text Available Haya Ascher-Svanum, Alan JM Brnabic, Anthony H Lawson, Bruce J Kinon, Virginia L Stauffer, Peter D Feldman, Katarina KelinLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USAAbstract: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients’ clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0–14 days prior and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%. Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions–Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient’s worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians’ stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research

  19. Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Knop, Filip Krag; Madsen, Anna

    2014-01-01

    levels, non-diabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite regulating hormones, GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight...

  20. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    Science.gov (United States)

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Drug: D02682 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01941 ... Benzamide antipsychotic ... DG01478 ... Dopamine antagonist ... DG01474 ... Dopamine D2-receptor antagonist A... D02682 Drug Remoxipride (USAN) ... C16H23BrN2O3 D02682.gif ... Neuropsychiatric agent

  2. Use of Academic Detailing With Audit and Feedback to Improve Antipsychotic Pharmacotherapy.

    Science.gov (United States)

    Brunette, Mary F; Cotes, Robert O; de Nesnera, Alexander; McHugo, Gregory; Dzebisashvili, Nino; Xie, Haiyi; Bartels, Stephen J

    2018-06-08

    Second-generation antipsychotics vary in their propensity to cause serious cardiometabolic side effects. In addition, use of two or more antipsychotics (polypharmacy) may lead to additive side effects and has not been shown to be consistently more effective than monotherapy. This study examined the use of academic detailing with audit and feedback to improve antipsychotic prescribing practices, including antipsychotic polypharmacy and utilization of medication with high or low risk of cardiometabolic side effects ("high risk" or "low risk," respectively). Four intervention sessions were provided over two years to psychiatric care providers at community mental health centers. Segmented regression within the general estimating equation model framework used Medicaid pharmacy claims to examine prescribing patterns before and after the intervention among all beneficiaries (67,721 person-months) over a five-year period. After the intervention, 10.9% of beneficiaries with antipsychotic claims were on polypharmacy, compared with 13.1% before the invention. Use of high-risk and low-risk antipsychotics did not change. The final adjusted polypharmacy model showed that antipsychotic polypharmacy decreased among young adults and adults ages 40 or older compared with beneficiaries ages 30-39 (β=-.02, p=.04, and β=-.02, p=.007, respectively). The raw proportion of beneficiaries on high- and low-risk agents did not change, although final adjusted models demonstrated changes in use of high- and low-risk agents by diagnosis and risk group. Polypharmacy decreased among young and older adults after academic detailing with audit and feedback. Although further research is needed, this low-intensity intervention may help mental health systems reduce antipsychotic polypharmacy.

  3. Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Azekawa T

    2011-11-01

    Full Text Available Takaharu Azekawa, Shizuko Ohashi, Akira ItamiShioiri Mental Clinic, Yokosuka-shi, Kanagawa-ken, JapanBackground: Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting.Methods: Using a retrospective cohort study design, we screened all outpatients (n = 7936 who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703 diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic.Results: Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant.Conclusion: Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.Keywords: retrospective study, second-generation antipsychotics, effectiveness, treatment continuation, schizophrenia, aripiprazole

  4. Association between unemployment rates and prescription drug utilization in the United States, 2007–2010

    Science.gov (United States)

    2012-01-01

    Background While extensive evidence suggests that the economic recession has had far reaching effects on many economic sectors, little is known regarding its impact on prescription drug utilization. The purpose of this study is to describe the association between state-level unemployment rates and retail sales of seven therapeutic classes (statins, antidepressants, antipsychotics, angiotensin-converting enzyme [ACE] inhibitors, opiates, phosphodiesterase [PDE] inhibitors and oral contraceptives) in the United States. Methods Using a retrospective mixed ecological design, we examined retail prescription sales using IMS Health Xponent™ from September 2007 through July 2010, and we used the Bureau of Labor Statistics to derive population-based rates and mixed-effects modeling with state-level controls to examine the association between unemployment and utilization. Our main outcome measure was state-level utilization per 100,000 people for each class. Results Monthly unemployment levels and rates of use of each class varied substantially across the states. There were no statistically significant associations between use of ACE inhibitors or SSRIs/SNRIs and average unemployment in analyses across states, while for opioids and PDE inhibitors there were small statistically significant direct associations, and for the remaining classes inverse associations. Analyses using each state as its own control collectively exhibited statistically significant positive associations between increases in unemployment and prescription drug utilization for five of seven areas examined. This relationship was greatest for statins (on average, a 4% increase in utilization per 1% increased unemployment) and PDE inhibitors (3% increase in utilization per 1% increased unemployment), and lower for oral contraceptives and atypical antipsychotics. Conclusion We found no evidence of an association between increasing unemployment and decreasing prescription utilization, suggesting that any

  5. Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

    Science.gov (United States)

    Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

    2003-01-01

    Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment ( 12 weeks) are lacking. Our results suggest that none of the atypical

  6. New users of antipsychotic medication: A population-based cohort study of occupational outcome measures in relation to antipsychotic on-label and off-label prescribing practices

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    BACKGROUND: Treatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing ...

  7. Glutamatergic and GABAergic disturbances as markers of choice-of-treatment – part of Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II)

    DEFF Research Database (Denmark)

    Bojesen, Kirsten Borup; Jessen, Kasper; Rostrup, Egill

    Background Insufficient response to antipsychotic drugs constitutes a major challenge in the treatment of patients with schizophrenia and other targets than the dopamine D2 receptors are highly warranted. Twenty to thirty % of patients do not respond sufficiently to antipsychotic medication, whic...... Inclusion started the 1st of January 2014 and is expected to continue until December 2018. So far 3 patients have been included. Analysis of data has not yet taken place. For more information about the project or referral of patients, please contact: Kirsten Borup Bojesen at Kirsten...

  8. Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline.

    Science.gov (United States)

    Hellings, Jessica A; Arnold, L Eugene; Han, Joan C

    2017-04-01

    Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. Areas covered: We review dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD. The older antipsychotic loxapine is discussed in terms of preliminary albeit limited evidence in ASD. Emerging promise of amitriptyline in ASD is discussed, together with promising BDNF effects of loxapine and amitriptyline. Expert opinion: In ASD, pharmacotherapy and specifically dopamine antagonist drugs are often prescribed for challenging behaviors including aggression. The novel antipsychotics risperidone and aripiprazole have received most study in ASD and are FDA-approved for irritability in children with ASD over age 5 years; individuals with ASD are prone to weight gain, Type II diabetes and associated side effects. Low dose loxapine has properties of classical and novel antipsychotics but importantly appears more weight neutral, and with promising use in adolescents and adults with ASD. Amitriptyline appears effective in ASD for irritability, aggression, gastrointestinal problems, and insomnia, in children, adolescents and adults however our adult data on amitriptyline in ASD is still in preparation for publication. Both loxapine and amitriptyline may stimulate BDNF; further studies are warranted.

  9. Antipsychotics, brain morphology and duration of untreated illness in schizophrenia

    NARCIS (Netherlands)

    Boonstra, G.

    2011-01-01

    Aims: This thesis addresses the necessity of prophylactic antipsychotic treatment in first-episode schizophrenia patients and the effect of discontinuation of antipsychotics on brain volume and side-effects as well as the usage of these medications in general practice. Furthermore, the influence of

  10. Efficacy of antipsychotic agents at human 5-HT(1A) receptors determined by [3H]WAY100,635 binding affinity ratios: relationship to efficacy for G-protein activation.

    Science.gov (United States)

    Newman-Tancredi, A; Verrièle, L; Touzard, M; Millan, M J

    2001-10-05

    5-HT(1A) receptors are implicated in the aetiology of schizophrenia. Herein, the influence of 15 antipsychotics on the binding of the selective 'neutral' antagonist, [3H]WAY100,635 ([3H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)-cyclo-hexanecarboxamide), was examined at human 5-HT(1A) receptors expressed in Chinese Hamster Ovary cells. In competition binding experiments, 5-HT displayed biphasic isotherms which were shifted to the right in the presence of the G-protein uncoupling agent, GTPgammaS (100 microM). In analogy, the isotherms of ziprasidone, quetiapine and S16924 (((R-2-[1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yloxy)-ethyl]-pyrrolidin-3yl]-1-(4-fluoro-phenyl)-ethanone), were displaced to the right by GTPgammaS, consistent with agonist actions. Binding of several other antipsychotics, such as ocaperidone, olanzapine and risperidone, was little influenced by GTPgammaS. Isotherms of the neuroleptics, haloperidol, chlorpromazine and thioridazine were shifted to the left in the presence of GTPgammaS, suggesting inverse agonist properties. For most ligands, the magnitude of affinity changes induced by GTPgammaS (alteration in pK(i) values) correlated well with their previously determined efficacies in [35S]GTPgammaS binding studies [Eur. J. Pharmacol. 355 (1998) 245]. In contrast, the affinity of the 'atypical' antipsychotic agent, clozapine, which is a known partial agonist at 5-HT(1A) receptors, was less influenced by GTPgammaS. When the ratio of high-/low-affinity values was plotted against efficacy, hyperbolic isotherms were obtained, consistent with a modified ternary complex model which assumes that receptors can adopt active conformations in the absence of agonist. In conclusion, modulation of [3H]-WAY100,635 binding by GTPgammaS differentiated agonist vs. inverse agonist properties of antipsychotics at 5-HT(1A) receptors. These may contribute to differing profiles of antipsychotic activity.

  11. Decreased left middle temporal gyrus volume in antipsychotic drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.

    Science.gov (United States)

    Hu, Maorong; Li, Jun; Eyler, Lisa; Guo, Xiaofeng; Wei, Qingling; Tang, Jingsong; Liu, Feng; He, Zhong; Li, Lihua; Jin, Hua; Liu, Zhening; Wang, Juan; Liu, Fang; Chen, Huafu; Zhao, Jingping

    2013-03-01

    The shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover gray matter volume differences in patients with schizophrenia and their unaffected siblings with voxel-based morphometry (VBM). We recruited antipsychotic drug-naive, first-episode schizophrenia (FES) patients, their unaffected siblings and age-, sex- and handedness-matched healthy controls. We used VBM to investigate differences in gray matter volume among the 3 groups. There were significant gray matter volumetric differences among the 3 groups in bilateral hippocampal and parahippocampal gyri, bilateral middle temporal gyri, and superior temporal gyri (FDR ptemporal gyrus, and volume of this region was not different between siblings and patients. Our findings confirm and extend previous VBM analyses in schizophrenia and it indicate that schizophrenia may be characterized by an abnormal development of cerebral lateralization. Furthermore, these data argue that patients and their unaffected siblings might share decreases in the gray matter volume of the left middle temporal gyrus, and this regional reduction might be a potential endophenotype for schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Foster care, externalizing disorders, and antipsychotic use among Medicaid-enrolled youths.

    Science.gov (United States)

    Vanderwerker, Lauren; Akincigil, Ayse; Olfson, Mark; Gerhard, Tobias; Neese-Todd, Sheree; Crystal, Stephen

    2014-10-01

    The authors investigated the extent to which clinical diagnoses of externalizing disorders explain higher rates of antipsychotic use by foster care youths. Medicaid claims data from 44 states for 2009 for youths in foster care (N=301,894) and those not in foster care (N=5,092,574) were analyzed, excluding those with schizophrenia, bipolar disorder, autism, and major depressive disorder. Logistic regressions assessed the relationship between foster care, externalizing disorders, and antipsychotic use. Foster care youths had higher rates of externalizing disorders than the comparison group (attention-deficit hyperactivity disorder, 17.3% versus 6.5%; disruptive behavior disorder, 7.2% versus 2.5%; conduct disorder, 2.3% versus .5%) and greater antipsychotic use (7.4% versus 1.4%). Foster care remained a significant predictor of antipsychotic use after control for demographic and diagnostic covariates, including externalizing disorders (adjusted odds ratio=2.59, 95% confidence interval=2.54-2.63). High rates of externalizing disorder diagnoses only partially explained elevated levels of antipsychotic use in this vulnerable population.

  13. Effects of Psychosocial Interventions for Behavioral and Psychological Symptoms in Dementia on the Prescription of Psychotropic Drugs: A Systematic Review and Meta-Analyses.

    Science.gov (United States)

    Birkenhäger-Gillesse, Elizabeth G; Kollen, Boudewijn J; Achterberg, Wilco P; Boersma, Froukje; Jongman, Lydia; Zuidema, Sytse U

    2018-03-01

    Dementia is often accompanied by neuropsychiatric symptoms. Psychotropic drugs for the treatment of neuropsychiatric symptoms are frequently used to manage these problems, but they are of limited effectiveness and can have serious side effects. Psychosocial interventions are advocated as first line treatment and may help to reduce psychotropic drug use. To assess the effect of multidisciplinary psychosocial interventions in nursing homes on the psychotropic drug prescription rate. Literature obtained from searches in 9 electronic databases was systematically reviewed. In addition, the pooled effects of specific psychosocial interventions in homogenous subgroups were analyzed (meta-analysis). Eleven randomized controlled studies that investigated multiple psychotropic drugs interventions (psychotropic drugs in 3, antipsychotics in 9, and antidepressants in 5 studies) as well as different types of psychosocial interventions were included. We separately analyzed interventions directed at the care staff level (educational programs in 3, in-reach services or consultation in 1, cultural or process change in 6 studies) and the individual resident level in 1 study. In 7 out of 9 studies reporting on antipsychotic drug use, the physician was actively involved. Nine studies in which antipsychotic drug use was specified reported a significant decrease in prescription rate as a result of psychosocial interventions [relative risk (RR) 0.71, 95% confidence interval (CI) 0.59-0.88], whereas meta-analysis of 5 studies investigating antidepressant drug use failed to show a significant effect (RR 0.82, 95% CI 0.64-1.02). Pooled effect sizes of 6 studies investigating cultural change, showed a significant decrease in antipsychotic drug use (RR 0.65, 95% CI 0.57-0.73). Effect sizes of 2 studies on educational programs on antipsychotic use were nonsignificant (RR 1.50, 95% CI 0.49-4.64). Sensitivity analysis of 7 studies reporting on antipsychotic drug use involving prescribing

  14. A Study of the Impact of Cannabis on Doses of Discharge Antipsychotic Medication in Individuals with Schizophrenia or Schizoaffective Disorder.

    Science.gov (United States)

    Babatope, Taiwo; Chotalia, Jigar; Elkhatib, Rania; Mohite, Satyajit; Shah, Joel; Goddu, Sumana; Patel, Ruchir Arvind; Aimienwanu, Osarhiemen Ruth; Patel, Devanshu; Makanjuola, Titilayo; Okusaga, Olaoluwa O

    2016-12-01

    Patients with schizophrenia or schizoaffective disorder have a high prevalence of comorbid cannabis use disorder (CUD). CUD has been associated with poorer outcomes in patients. We compared doses of antipsychotic medications at the time of discharge from hospital among inpatients with schizophrenia or schizoaffective disorder with or without concurrent cannabis use. We reviewed the medical records of patients (N = 8157) with schizophrenia or schizoaffective disorder discharged from the hospital between 2008 and 2012. The patients were divided into two groups; those with urine drug tests positive for cannabis and those negative for cannabis. Doses of antipsychotic medications were converted to chlorpromazine equivalents. Bivariate analyses were done with Student's t test for continuous variables and χ 2 test for categorical variables. Linear regression was carried out to adjust for potential confounders. Unadjusted analysis revealed that the cannabis positive group was discharged on lower doses of antipsychotic medication compared with the cannabis negative group (geometric mean chlorpromazine equivalent doses 431.22 ± 2.20 vs 485.18 ± 2.21; P schizoaffective disorder.

  15. Aripiprazole in schizophrenia and schizoaffective disorder: A review.

    Science.gov (United States)

    Stip, Emmanuel; Tourjman, Valérie

    2010-01-01

    During the past decade, there has been some progress in the pharmacotherapy of schizophrenia and schizoaffective disorder. Current evidence supports the use of various second-generation, or atypical, antipsychotic medications, although few of these agents have been associated with long-term efficacy and tolerability. Aripiprazole is an atypical antipsychotic that has been found to improve positive and negative symptoms of schizophrenia with a favorable adverse-effect profile. This article reviews the efficacy and tolerability of aripiprazole in the context of recommended management strategies for schizophrenia and schizoaffective disorder, and in comparison with first-generation and other second-generation antipsychotics. A search of MEDLINE (1999-May 2009) was conducted for reports of short- and long-term clinical studies of atypical antipsychotics (including aripiprazole) and meta-analyses of randomized controlled trials comparing first- and second-generation antipsychotics (including aripiprazole) in the treatment of schizophrenia or schizoaffective disorder. The search terms were schizophrenia; schizoaffective disorder; pharmacogenetics; adverse effects; tardive dyskinesia AND atypical antipsychotics; aripiprazole; aripiprazole, schizophrenia, AND double-blind studies; and atypical antipsychotics AND adverse effects. The reference lists of identified articles were reviewed for additional relevant publications. Only full study publications were included. Based on the clinical evidence, including data from short-term (4-8 weeks) and long-term (26-52 weeks) randomized, double-blind clinical trials, aripiprazole has been associated with improvements in positive, negative, cognitive, and affective symptoms of schizophrenia and schizoaffective disorder. It has been associated with long-term (up to 52 weeks) symptom control in schizophrenia, as well as with efficacy in treatment-resistant schizophrenia. Common adverse effects associated with aripiprazole were nausea

  16. Proline-induced changes in acetylcholinesterase activity and gene expression in zebrafish brain: reversal by antipsychotic drugs.

    Science.gov (United States)

    Savio, L E B; Vuaden, F C; Kist, L W; Pereira, T C; Rosemberg, D B; Bogo, M R; Bonan, C D; Wyse, A T S

    2013-10-10

    Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0mM) during 1h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 μM) were tested. Long-term proline exposures significantly increased AChE activity for both treated groups when compared to the control (34% and 39%). Moreover, the proline-induced increase on AChE activity was completely reverted by acute administration of antipsychotic drugs (haloperidol and sulpiride), as well as the changes induced in ache expression. When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Second-generation antipsychotic and diabetes mellitus in children and adolescents

    Directory of Open Access Journals (Sweden)

    Carlo Ripoli

    2017-12-01

    Full Text Available Second generation antipsychotics (SGA are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before, clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety.

  18. The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

    Science.gov (United States)

    Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus

    2015-01-01

    Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle

  19. Antipsychotic Selection for Acute Agitation and Time to Repeat Use in a Psychiatric Emergency Department.

    Science.gov (United States)

    Gomez, Seth; Dopheide, Julie

    2016-11-01

    Early recognition and treatment of agitated patients is essential to avoid violence in the psychiatric emergency department (ED). Antipsychotics have established efficacy in managing agitation, yet little is known about how the choice of initial antipsychotic impacts time to repeat use and length of stay (LOS) in the psychiatric ED. To describe the impact of initial antipsychotic selection on time to repeat use and LOS in the psychiatric ED. A chart review identified 388 cases in which patients were administered an antipsychotic for agitation in the psychiatric ED between July 1 and August 31, 2014. Time to repeat use and LOS were compared for intramuscular (IM) haloperidol, other IM antipsychotics, and oral second-generation antipsychotics (SGAs) using the Kruskal-Wallis or Wilcoxon-Mann-Whitney test. Of the 388 cases, 31% (n=122) required repeat medications. Mean time to repeat use for IM haloperidol was 20.1±18.4 hours, which was not significantly different from mean time to repeat use in the groups receiving other IM antipsychotics or oral SGAs (P=0.35). The mean LOS was 29.7±28.7 hours for IM haloperidol, 30.3±36.9 hours for other IM antipsychotics, and 22.6±28.0 hours for oral SGAs. Significant differences in LOS between repeat and nonrepeat users of IM haloperidol and other IM antipsychotics were observed, but not among those who received oral SGAs. Mean time to repeat use ranged from 14 to 20 hours with IM haloperidol, other IM antipsychotics, and oral SGAs without significant differences in time to repeat use in the 3 different groups. Repeat users of IM antipsychotics had a significantly longer LOS in the ED compared with nonrepeat users of IM antipsychotics. However, patients who were initially administered oral SGAs did not have longer LOS in the ED even if a repeat dose was given.

  20. Extrastriatal dopamine D-2/3 receptors and cortical grey matter volumes in antipsychotic-naive schizophrenia patients before and after initial antipsychotic treatment

    DEFF Research Database (Denmark)

    Nørbak-Emig, Henrik; Pinborg, Lars H.; Raghava, Jayachandra M.

    2017-01-01

    OBJECTIVES: Long-term dopamine D2/3 receptor blockade, common to all antipsychotics, may underlie progressive brain volume changes observed in patients with chronic schizophrenia. In the present study, we examined associations between cortical volume changes and extrastriatal dopamine D2/3 recept...... binding potentials (BPND) in first-episode schizophrenia patents at baseline and after antipsychotic treatment. METHODS: Twenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [(123)I]epidepride single-photon emission computerised tomography (SPECT......), and psychopathology assessments before and after 3 months of treatment with either risperidone (N = 13) or zuclopenthixol (N = 9). Twenty healthy controls matched on age, gender and parental socioeconomic status underwent baseline MRI and SPECT. RESULTS: Neither extrastriatal D2/3 receptor BPND at baseline, nor...