Animal behavior models of the mechanisms underlying antipsychotic atypicality.

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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

Dislipidemias e antipsicóticos atípicos Dyslipidemias and atypical antipsychotics

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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

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.

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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.

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

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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

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

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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

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.

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

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

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

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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

Atypical antipsychotic usage among Asian Americans and Pacific Islanders.

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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.

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

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

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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)

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…

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

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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.

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

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

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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.

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

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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

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

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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.

THE ROLE OF ATYPICAL ANTIPSYCHOTIC DECREASING AGGRESIVENESS IN SCHIZOPHRENIA

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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.

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

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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.

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

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

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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

Atypical antipsychotics in the treatment of early-onset schizophrenia

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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

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

Stimulant and Atypical Antipsychotic Medications For Children Placed in Foster Homes

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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

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.

Aripiprazole versus other atypical antipsychotics for schizophrenia

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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

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

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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.

Antipsychotic prescribing in older people.

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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

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

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

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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.

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

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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

Amisulpride versus other atypical antipsychotics for schizophrenia

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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

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

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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.

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.

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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

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

Current status of atypical antipsychotics for the treatment of fibromyalgia.

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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.

Atypical antipsychotics for disruptive behaviour disorders in children and youths.

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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

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

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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.

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

Use of second-generation antipsychotic agents for sleep and sedation: a provider survey.

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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.

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.

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

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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.

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.

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

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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.

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

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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

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

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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.

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

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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.

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

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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…

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

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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.

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

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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.

Sertindole versus other atypical antipsychotics for schizophrenia

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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

Antipsychotic agents: efficacy and safety in schizophrenia

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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

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

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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.

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.

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

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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.

Diabetic control and atypical antipsychotics: a case report

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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.

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

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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.

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

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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.

Measurement of treatment adherence with antipsychotic agents in patients with schizophrenia

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Xinhua S Ren

2009-09-01

Full Text Available Xinhua S Ren1,2,3, Lawrence Herz4,5, Shirley Qian1,2,3, Eric Smith3,4, Lewis E Kazis1,2,31The Center for the Assessment of Pharmaceutical Practices (CAPP, Boston University School of Public Health, Boston, MA, USA; 2Department of Health Policy and Management, Boston University School of Public Health, Boston, MA, USA; 3Center for Health Quality, Outcomes, and Economic Research, Bedford Veterans Affairs Medical Center, Bedford, MA, USA; 4Division of Psychiatry, Boston University School of Medicine, Boston, MA, USA; 5Mental Health Service Line, Bedford VA Medical Center, Bedford, MA, USAAbstract: The importance of medication adherence in sustaining control of schizophrenic symptoms has generated a great deal of interest in comparing levels of treatment adherence with different antipsychotic agents. However, the bulk of the research has yielded results that are often inconsistent. In this prospective, observational study, we assessed the measurement properties of 3 commonly used, pharmacy-based measures of treatment adherence with antipsychotic agents in schizophrenia using data from the Veterans Health Administration during 2000 to 2005. Patients were selected if they were on antipsychotics and diagnosed with schizophrenia (N = 18,425. A gap of ≥30 days (with no filled index medication was used to define discontinuation of treatment as well as medication “episodes,” or the number of times a patient returned to the same index agent after discontinuation of treatment within a 1-year period. The study found that the 3 existing measures differed in their approaches in measuring treatment adherence, suggesting that studies using these different measures would generate different levels of treatment adherence across antipsychotic agents. Considering the measurement problems associated with each existing approach, we offered a new, medication episode-specific approach, which would provide a fairer comparison of the levels of treatment adherence

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.

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

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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

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

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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...

First Episode Schizophrenia Regional Cerebral Blood Flow Assessment after Atypical Antipsychotics

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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)

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.

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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.

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.

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.

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.

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...

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

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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…

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

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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.

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

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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.

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

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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

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

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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.

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

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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)

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

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.

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

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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.

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...

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.

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

Science.gov (United States)

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.

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).

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

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

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.

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...

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

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

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Acioly LT Lacerda

2002-03-01

disorder, especially in the acute manic phase. Recently new alternatives have become available with the development of newer atypical antipsychotic agents. A comprehensive Medline search was conducted, and all available literature concerning the role of atypical antipsychotics in the treatment of bipolar patients was retrieved. Olanzapine showed to be quite effective in the treatment of acute mania, and it was found that an average of 63.5% of the patients had a significant improvement in double blind controlled studies, with weight gain as the major side effect. Data was less robust for clozapine and risperidone, mainly due to methodological limitations of the few available studies. It was also found a considerable interest in future investigating the efficacy of these pharmacological agents in refractory cases and in the treatment of the disorder's depressive phase. Additionally, there has been extensive interest in evaluating their potential action as mood stabilizers, for which there will be a need of longer-term longitudinal studies.

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

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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.

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

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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.

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

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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

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

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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...

The Seropositivity Rate of Atypical Agents in Patients with Community-Acquired Pneumonia

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Ruhan Karakoc Gunes

2007-08-01

Full Text Available The aim of this study was to investigate the IgM antibody positivities of atypical pneumonia agents in patients with community-acquired pneumonia (CAP, and to compare the results with controls. The serum samples which were collected from 87 adult patients and 21 healthy controls have been investigated by a commercial ELISA (Pneumobact ELISA IgM, Vircell, Spain in which four different atypical pneumonia agents were fixed onto a slide. In the patients group, IgM positivity rates for the agents were as follows, respectively; 2.3% for Legionella pneumophila, 56.3% Chlamydia pneumoniae, 33.3% for Mycoplasma pneumoniae, 9.2% for Coxiella burnetii. The rates of IgM positivities in the control group varied 7% for all of the agents except M. Pneumoniae and C. Pneumoniae and 2 of these controls were positive for L. Pneumophila IgM, one was positive for C. Burnetii IgM. According to the statistical evaluation, there were significant differences for IgM seropositivities to Mycoplasma pneumoniae and Chlamydia Pneumoniae,between the patient and the control groups (p0.05. We showed that the seropositivity rate of atypical agents in patients with CAP was significantly higher when compared to healthy control group. This result suggests us, atypical agents might be responsible in CAP patients in a great amount. Furthermore, our study also suggests that clinical and radiological findings are not useful for discriminating atypical from typical pneumonia. [TAF Prev Med Bull 2007; 6(4.000: 279-284

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

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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

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

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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.

Relationship between antipsychotic medication, obesity and cognitive functions

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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.

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

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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.

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 ...

Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

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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.

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

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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.

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.

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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.

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

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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

Antipsychotic prescription patterns and treatment costs of ...

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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.

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

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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

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

Risperidone versus other atypical antipsychotics for schizophrenia

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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

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

La valutazione economica del trattamento farmacologico con antipsicotici nella schizofrenia: una revisione sistematica della letteratura

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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.

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

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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

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

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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

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

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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.

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.

Novel versus conventional antipsychotic drugs.

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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.

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

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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

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

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

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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.

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

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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

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

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.

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.

Movement disorders in elderly users of risperidone and first generation antipsychotic agents: a Canadian population-based study.

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Irina Vasilyeva

Full Text Available Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines, particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results.A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS in new users of risperidone compared to new users of FGAs.After controlling for potential confounders (demographics, comorbidity and medication use, risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22-0.67; 0.45, 95% CI: 0.28-0.73; 0.50, 95% CI: 0.33-0.77; 0.65, 95% CI: 0.45-0.94, respectively. At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54-1.05.In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

Metabolic Signature of Antipsychotics Used in the Treatment of Autism

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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

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

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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.

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

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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.

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

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.

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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.

Manual or automated measuring of antipsychotics' chemical oxygen demand.

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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.

Quetiapine versus other atypical antipsychotics for schizophrenia

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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

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

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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.

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

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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.

Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

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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

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

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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....

Metabolic Signature of Antipsychotics used in the Treatment of Autism

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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

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.

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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.

Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

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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.

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.)

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

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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....

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

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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...

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

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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

Models of treatment with antipsychotics of the schizophrenic patients

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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

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

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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.

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

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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.

Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

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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.

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

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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.

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

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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

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

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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.

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

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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

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

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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

Use of Academic Detailing With Audit and Feedback to Improve Antipsychotic Pharmacotherapy.

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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.

Body weight gain induced by a newer antipsychotic agent reversed as negative symptoms improved.

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Koga, M; Nakayama, K

2005-07-01

We describe a patient in whom improvement in negative symptoms contributed to early weight loss and subsequent long-term improvement in weight management. Case report. A 26-year-old woman with schizophrenia gained 7 kg over the course of 1 year after starting treatment with olanzapine. However, as negative symptoms gradually improved with treatment, she became motivated to diet and exercise regularly. She quickly lost 9 kg and subsequently maintained optimal weight (55 kg; body mass index, 24.1 kg/m(2) ). Important strategies for minimizing weight gain in patients taking antipsychotic agents include improving negative symptoms of avolition and apathy, regular monitoring of body weight and potential medical consequences of overweight and obesity, and educating the patient about the importance of diet and regular exercise.

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

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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.)

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

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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.

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

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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.

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

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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.

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

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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

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

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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

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

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.

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

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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.

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...

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.

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

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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

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.

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

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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.

Effect of second-generation antipsychotics on employment and productivity in individuals with schizophrenia: an economic perspective.

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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

METHODS ELABORATION ON DETECTION OF SOME ATYPICAL NEUROLYTIC AGENTS FOR CHEMICAL AND TOXICOLOGICAL ANALYSIS

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I. P. Remezova

2014-01-01

Full Text Available It is necessary to elaborate methods of atypical neuroleptic agents detection as individual substances and in different combinations as well for diagnosis of poisoning by some of them: clozapine, risperidone, sertindole, olanzapine, aripiprazole. The purpose of this work is methods elaboration of detection of clozapine, risperidone, sertindole, olanzapine, aripiprazole, haloperidol, oxazepam, carbamazapine using TLC, HPLC and UV spectrophotometry methods. During this work we used tablet forms of clozapine, risperidone, sertindole, olanzapine, aripiprazole. It is possible to use solution systems like ethanol-water-25% ammonia solution (8:1:1, toluolacetone-ethanol-25% ammonia solution (45:45:7.5:2.5, dioxan-chloroform-acetone-25% ammonia solution (47.5:45:5:2.5 for preliminary examination of atypical neuroleptic agents under study in combination with typical neuroleptics and tranquilizers with undirected analysis (general screening. System of solvents ethyl-acetate-chloroform-25% ammonia solution (85:10:5 is recommended to use for individual screening of risperidone, sertindole, olanzapine, haloperidol, benzol-ethanol-25% ammonia solution (50:10:0.5 system to use for clozapine, sertindole, olanzapine. Ethanol-25% ammonia solution (100:1.5 system is reasonable to use for chromatographic clearance of extracts from biological substances under study. We recommend using HPLC method and UV spectrophotometry for carrying out of a principal examination of clozapine, risperidone, sertindole, olanzapine and aripiprazole in case one of the substances under study is determined in the object.

Schizophrenia: a review of neuropharmacology.

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Lyne, J; Kelly, B D; O'Connor, W T

2004-01-01

The last few decades have seen significant advances in our understanding of the neurochemical basis of schizophrenia. To describe the neurotransmitter systems and nerve circuits implicated in schizophrenia; to compare the neuropharmacology of typical and atypical anti-psychotic agents; and to describe recent developments in the pharmacological treatment of schizophrenia. Relevant pharmacological, neurophysiological and psychiatric literature was examined and reviewed. Schizophrenia is associated with abnormalities of multiple neurotransmitter systems, including dopamine, serotonin, gamma-aminobutyric acid and glutamate. Typical and atypical antipsychotic agents differ in their receptor-binding affinities, which are related to their differing side-effect profiles. Novel therapeutic strategies include normalisation of synaptic dopamine or serotonin levels, serotonin receptor antagonism and modulation of cerebral protein synthesis. The ideal treatment for schizophrenia may not be a single pharmacological agent but several agents that match the different expressions of the illness, in combination with psycho-social interventions.

Doubtful association of antipsychotic polypharmacy and high dosage with cognition in chronic schizophrenia.

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Kontis, Dimitrios; Theochari, Eirini; Kleisas, Spyridon; Kalogerakou, Stamatina; Andreopoulou, Angeliki; Psaras, Rafael; Makris, Yannis; Karouzos, Charalambos; Tsaltas, Eleftheria

2010-10-01

Despite consistent recommendations for antipsychotic monotherapy, antipsychotic polypharmacy (the use of two or more antipsychotic agents) and the administration of excessive doses (higher than 1000 mgr/day of chloropromazine equivalents) is a common practice in schizophrenia. The therapeutic and adverse effects of this practice are poorly studied, in particular with regards to the cognitive symptoms of the disease. In this cross-sectional study we investigated the cognitive effects of antipsychotic polypharmacy and excessive doses in 53 patients with chronic schizophrenia using non-verbal cognitive tasks involving speed of movement, memory and executive functions. No significant difference in performance scores was found between the groups under polypharmacy and monotherapy, or the groups receiving either excessive or normal doses of antipsychotics. Since these groups did not also differ in demographic, clinical, other pharmacologic parameters, in the relative anticholinergic potency of antipsychotics, or in intelligence scores, we raise doubts about the association of polypharmacy and excessive doses with non-verbal cognitive performance in chronic schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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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.

Side effects as influencers of treatment outcome.

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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.

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

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

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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.

Design, synthesis, spectroscopic characterization and anti-psychotic investigation of some novel Azo dye/Schiff base/Chalcone derivatives

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Chandravadivelu Gopi

2017-12-01

Full Text Available The purpose of the study is to design, synthesise and assess the antipsychotic activity of a set of the novel (5-(10-(3-N, N-Dimethylamino propyl-10H-phenothiazine-3-yl-1,3,4-thiadiazo-2-yl Azodye/Schiff base/Chalcone derivatives. The newly synthesised compound structure was characterised by FT-IR, 1H NMR, Mass spectroscopy and elemental analysis. Each compound has been shown an excellent anti-psychotic activity in a haloperidol-induced catalepsy metallic bar test. The results found are firmly similar to docking study. Among the synthesised derivatives, compound 2-Amino-6-(3-hydroxy-4-methylphenyl pyrimidine-4-yl (7-chloro-10-(3-(N, N-dimethylamino propyl-10H-phenothiazine-3-yl methanone (GC8 exhibiting high potency of catalepsy induction. Therefore, the derivative of GC8 has been considered that a potent anti-psychotic agent among the synthesised compounds. Keywords: Design, MVD, Catalepsy, Antipsychotic agent, X-ray crystallography

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

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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.

Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

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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

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

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

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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.

Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

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Ricardo Alberto Moreno

2004-10-01

effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics.

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

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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

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

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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.

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

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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.

[Study of Flexible Doses of Paliperidone ER in Pacients with Schizophrenia who Have Undergone Inefficient Treatment with other Antipsychotics].

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Córdoba, Rodrigo; Cano, Juan Fernando; Arango-Dávila, César Augusto; Miranda, Carlos; Holguín, Jorge; Fernández, Darío; Márquez, Miguel; Lupo, Christian; Gargoloff, Pedro; Petracca, Gustavo; Lucchetti, César

2012-06-01

Extended-release (ER) paliperidone is an innovative atypical antipsychotic that allows minimal peak-to-through fluctuations with once-daily dosing. To evaluate effectiveness, safety and tolerability of flexible, once-daily doses of paliperidone ER (3-12 mg/day) in patients with schizophrenia from Argentina and Colombia who had previously failed treatment with other antipsychotic agents. The authors conducted a 6-month, open-label, prospective and multicentric study. Effectiveness was assessed with Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Other measures of effectiveness, safety and tolerability, were also conducted. Paliperidone ER 3-12 mg/day improved Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint) from baseline to study end (p < 0,001). In the PANSS total score, the mean change from baseline (83, 9 units) to end point (53,7 units) was significant (p < 0,001). Flexible doses of paliperidone ER demonstrated a ≥20% reduction in the PANSS total score (p<0.001) in almost two-thirds of patients. PSP mean change from baseline (52 units) to end point (85 units) was significant (p < 0,001). Secondary effectiveness assessments, as well as safety and tolerability measures, demonstrated favourable results throughout the study. Flexible doses of paliperidone ER over 6 months were effective, safe and well tolerated in patients with schizophrenia from Argentina and Colombia. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

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

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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.

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

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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.

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

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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.

Biological treatment of acute agitation or aggression with schizophrenia or bipolar disorder in the inpatient setting.

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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

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

Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior.

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Tang, Yan; Chang, Chung-Chou H; Lave, Judith R; Gellad, Walid F; Huskamp, Haiden A; Donohue, Julie M

2016-03-01

regularly prescribing a therapeutic category, some physicians rely heavily on a small number of agents. Health systems may need to offer educational interventions to clinicians in order to improve their ability to tailor treatment decisions to the needs of individual patients. Future studies should examine the impact of the diversity of antipsychotic prescribing to determine whether more diversified prescribing improves patient adherence and outcomes.

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

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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.

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

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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.

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

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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.

Aripiprazole in schizophrenia and schizoaffective disorder: A review.

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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

[Neurotensin-like oligopeptides as potential antipsychotics: effect on dopamine system].

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Kost, N V; Meshavkin, V K; Batishcheva, E Iu; Sokolov, O Iu; Andreeva, L A; Miasoedov, N F

2011-01-01

According to published data, peptide neurotensin is considered as endogenous antipsychotic agent. A series of oligopeptides have been synthesized based on the proposed active center of neurotensin. These oligopeptides (called neurotensin-like peptides, NLPs) have been studied on behavioral models, in which the functional state of the dopamine system of animals was modified by apomorphine injections. The results of verticalization, stereotypy, and yawning tests revealed NLPs that behave as antagonists of dopamine receptors. Radioligand analysis showed that these peptides compete for specific binding to these receptors with sulpiride, which is a D2-type selective antagonist of dopamine receptors. The high degree of NLPs efficiency manifested in the behavioral tests and radioligand analysis suggests that the their antipsychotic action can be mediated by dopamine receptors.

MANAGEMENT OF DELIRIUM

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Helena Korošec Jagodič

2009-09-01

Conclusions Most recommendations for management of delirium are based on the nonpharmacological supportive care and prevention of delirium. It is also necessary to identify and treat the underlying causes. Antipsychotics are the mainstay of symptomatic pharmacological treatment and have been shown to be effective in treating symptoms of both hyperactive and hypoactive delirium. Although efficacy rates between typical and atypical antipsychotic agents are similar, the later are associated with fewer extrapyramidal side effects. Benzodiazepines are usually preferred for withdrawal delirium or as an alternative or adjuvant to antipsychotics when these are ineffective or cause unacceptable side effects.

Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity.

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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.

Treatment patterns and clinical characteristics prior to initiating depot typical antipsychotics for nonadherent schizophrenia patients

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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

Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on Agitation in Nursing Home Residents With Alzheimer Dementia.

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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.

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

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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.

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.

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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.

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

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

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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

Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists' survey in India.

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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.

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...

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

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

Bitropic D3 Dopamine Receptor Selective Compounds as Potential Antipsychotics.

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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

Clozapine-induced rabbit syndrome: a case report

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Cicek Hocaoglu

2009-10-01

Full Text Available Rabbit syndrome (RS is an antipsychoticinduced rhythmic motion of the mouth/lips resembling the chewing movements of a rabbit. The movement consists of a vertical-only motion, at about 5 Hz, with no involvement of the tongue. Long-term exposure to typical antipsychotics has clearly been associated with RS, but little is known of the risk of RS due to exposure to newer atypical antipsychotics. There have been isolated reports of RS in patients treated with the atypical agents risperidone, aripiprazole, olanzapine, and clozapine. We present the case history of a 44-year old female patient treated for paranoid schizophrenia for 22 years and RS during her last 10-month clozapine treatment. Background information from the literature is also discussed.

Antipsychotic Management of Schizoaffective Disorder: A Review.

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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

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

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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.

Evaluation and treatment of acute psychosis in children with Systemic Lupus Erythematosus (SLE): consultation-liaison service experiences at a tertiary-care pediatric institution.

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Muscal, Eyal; Nadeem, Tania; Li, Xiofan; Mian, Ayesha; Harris, Toi Blakley

2010-01-01

Neurological and psychiatric manifestations of systemic lupus erythematosus (SLE) are prevalent in children with SLE. There are few data on the evaluation and management of psychotic features in children with this systemic autoimmune disorder. The authors describe contemporary Child and Adolescent Psychiatry Consultation and Liaison service management of acute psychosis in children with lupus. The authors reviewed the records (2003-2008) of all pediatric SLE inpatients who were administered a traditional or atypical antipsychotic agent. They describe clinical features, initial and discharge mental status examinations, and inpatient psychotropic medication usage. Ten pediatric SLE patients (age 10-19 years) required psychiatric management for psychosis during the review period. Paranoid delusions (70%), visual hallucinations (60%), and auditory hallucinations (60%) were the most common psychotic symptoms documented. All children were initially treated with an antipsychotic medication. Seven children were maintained on an atypical antipsychotic during their hospitalization. Two children had extrapyramidal signs, but no other adverse events were documented. All children were improved at discharge, and 40% had complete resolution of psychosis; 8 of the 10 patients were discharged on a psychotropic medication. Psychotic manifestations associated with severe disease presentations were successfully treated by child psychiatrists. Atypical antipsychotics were well-tolerated and used as an adjunct to immunosuppressive regimens in these patients. Prospective studies are necessary to improve the care of children and adolescents with SLE and severe psychiatric manifestations.

Incident users of antipsychotics

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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...

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

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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.

Dyslipidaemia and Medical Outcome (Health Related Quality of Life in Patients with Schizophrenia Taking Antipsychotics in Enugu, Nigeria

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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.

Antipsychotic treatment among youth in foster care.

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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.

Antipsychotics and physical attractiveness.

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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.

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.

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

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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.

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

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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.

[Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

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Watanabe, Ken

2009-01-01

The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation

Antipsychotic-induced somnolence in mothers with schizophrenia.

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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.

Atypical manifestations of early syphilis

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R V Koranne

1990-01-01

Full Text Available A study of 36 untreated patients with early syphilis revealed atypical variations namely; long incubation period of 101 days in I patient, more than 3 chancres in 1, undermined margin of the chancre along with tenderness in 1 and moderate to severe tenderness of the ulcers in 2 cases. In 3 patients there was no indurations of the ulcers. Three patients with primary syphilis had unilateral lymphadenitis, and in I case the lymph nodes were not only tender but showed tendency towardsmatingawell. Insecondarysyphilis, 11 out of 16 patients having condylomata lata had no other muco-cutaneous lesions. Concomitant presence of other venereal disease to account for the atypical manifestations was discounted- by appropriate laboratory tests, response to therapeutic agents and follow up.

Atypical antipsychotics as add-on treatment in late-life depression

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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

Antipsychotic interventions in prodromal psychosis: safety issues.

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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

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...

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

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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.

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

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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.

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

Synthesis of {sup 13}C- and {sup 14}C-labeled 1192U90, an ortho-amino benzamide with a preclinical atypical antipsychotic profile

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Norman, M.H.; Gabriel, S.D. [Glaxo Wellcome Inc., Research Triangle Park, NC (United States)

1996-03-01

Three isotopic forms of potential antipsychotic agent 1192U90 (2-amino-N-(4-(4-(1,2-benzisthiazol-3-yl)-piperazinyl)butyl)benzam ide) were synthesized: one containing {sup 13}C-isotopes and two containing {sup 14}C-isotopes. The compound in which the ortho-amino benzamide ring is completely {sup 13}C-labeled was prepared in a four-step sequence starting from [{sup 13}C{sub 6}]aniline. The {sup 14}C-labeled compounds were prepared by methods analogous to those previously described for the unlabeled material. The key step involved the condensation of 3-(4-(4aminobutyl)-1-piperazinyl)-1,2-benzisothiazole with isatoic anhydride. The first {sup 14}C-labeled compound (3) was prepared from {sup 14}C-labeled 3-(4-(4-aminobutyl)-1-piperazinyl)-1,2-benzisothiazole, while the second compound (4) derived its isotopic label from [{sup 14}C]isatoic anhydride. Compound 3 had a specific activity of 26.55 mCi/mmol, a radiochemical purity of 99.3%, and a radiochemical yield of 3.4%. Compound 4 had a specific activity of 22.67 mCi/mmol and a radiochemical purity of 99.2%. (author).

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

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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.

Impact of Paliperidone Palmitate Versus Oral Atypical Antipsychotics on Health Care Resource Use and Costs in Veterans With Schizophrenia and Comorbid Substance Abuse.

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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.

Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal naturalistic approach.

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Castro-Fornieles, Josefina; Parellada, Mara; Soutullo, César A; Baeza, Immaculada; Gonzalez-Pinto, Ana; Graell, Montserrat; Paya, Beatriz; Moreno, Dolores; de la Serna, Elena; Arango, Celso

2008-08-01

The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months. Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months. Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.

Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study

DEFF Research Database (Denmark)

Baandrup, Lone; Gasse, Christiane; Jensen, Vibeke

2010-01-01

OBJECTIVE: Concomitant prescription of more than 1 antipsychotic agent (antipsychotic polypharmacy) in the treatment of schizophrenia is prevalent, although monotherapy is generally recommended. Mortality from natural causes is markedly increased in schizophrenia, and the role of polypharmacy...... remains controversial. The objective was to investigate if antipsychotic polypharmacy is associated with the excess mortality from natural causes among patients with schizophrenia. METHOD: A population-based nested case-control study was conducted using patient data from January 1, 1996, to December 31......, 2005, obtained from central Danish registers. From the study population of 27,633 patients with ICD-8- and ICD-10-diagnosed schizophrenia or other mainly nonaffective psychoses, aged 18-53 years, we identified 193 cases who died of natural causes within a 2-year period and 1,937 age- and sex...

Effects of Antipsychotics on Dentate Gyrus Stem Cell Proliferation and Survival in Animal Models: A Critical Update

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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.

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

Multiple Antipsychotic Medication Use in Autism Spectrum Disorder.

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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

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...

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.

Patient perspectives on antipsychotic treatments and their association with clinical outcomes

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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

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.

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 ...

Experimental transmission of atypical scrapie to sheep

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Spiropoulos John

2007-08-01

Full Text Available Abstract Background Active surveillance for transmissible spongiform encephalopathies in small ruminants has been an EU regulatory requirement since 2002. A number of European countries have subsequently reported cases of atypical scrapie, similar to previously published cases from Norway, which have pathological and molecular features distinct from classical scrapie. Most cases have occurred singly in flocks, associated with genotypes considered to be more resistant to classical disease. Experimental transmissibility of such isolates has been reported in certain ovinised transgenic mice, but has not previously been reported in the natural host. Information on the transmissibility of this agent is vital to ensuring that disease control measures are effective and proportionate. Results This report presents the successful experimental transmission, in 378 days, of atypical scrapie to a recipient sheep of homologous genotype with preservation of the pathological and molecular characteristics of the donor. This isolate also transmitted to ovinised transgenic mice (Tg338 with a murine phenotype indistinguishable from that of Nor 98. Conclusion This result strengthens the opinion that these cases result from a distinct strain of scrapie agent, which is potentially transmissible in the natural host under field conditions.

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...

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.

The Complex Relationship between Antipsychotic-Induced Weight Gain and Therapeutic Benefits: A Systematic Review and Implications for Treatment

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Alex T. Raben

2018-01-01

Full Text Available Background: Antipsychotic-induced weight gain (AIWG and other adverse metabolic effects represent serious side effects faced by many patients with psychosis that can lead to numerous comorbidities and which reduce the lifespan. While the pathophysiology of AIWG remains poorly understood, numerous studies have reported a positive association between AIWG and the therapeutic benefit of antipsychotic medications.Objectives: To review the literature to (1 determine if AIWG is consistently associated with therapeutic benefit and (2 investigate which variables may mediate such an association.Data Sources: MEDLINE, Google Scholar, Cochrane Database and PsycINFO databases were searched for articles containing all the following exploded MESH terms: schizophrenia [AND] antipsychotic agents/neuroleptics [AND] (weight gain [OR] lipids [OR] insulin [OR] leptin [AND] treatment outcome. Results were limited to full-text, English journal articles.Results: Our literature search uncovered 31 independent studies which investigated an AIWG-therapeutic benefit association with a total of 6063 enrolled individuals diagnosed with schizophrenia or another serious mental illness receiving antipsychotic medications. Twenty-two studies found a positive association while, 10 studies found no association and one study reported a negative association. Study variables including medication compliance, sex, ethnicity, or prior antipsychotic exposure did not appear to consistently affect the AIWG-therapeutic benefit relationship. In contrast, there was some evidence that controlling for baseline BMI/psychopathology, duration of treatment and specific agent studied [i.e., olanzapine (OLZ or clozapine (CLZ] strengthened the relationship between AIWG and therapeutic benefit.Limitations: There were limitations of the reviewed studies in that many had small sample sizes, and/or were retrospective. The heterogeneity of the studies also made comparisons difficult and publication bias

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

Antipsychotic Prescriptions for Children Aged 5 Years or Younger

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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.

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.

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

Atypical antipsychotics as augmentation therapy in anorexia nervosa.

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Enrica Marzola

Full Text Available Anorexia nervosa (AN is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings.

Isolation of Chlamydia abortus from a laboratory worker diagnosed with atypical pneumonia.

Science.gov (United States)

Ortega, Nieves; Caro, M Rosa; Gallego, M Carmen; Murcia-Belmonte, Antonio; Álvarez, Daniel; Del Río, Laura; Cuello, Francisco; Buendía, Antonio J; Salinas, Jesús

2015-01-01

Identifying the aetiological agent of atypical pneumonia in human can sometimes be a tedious process, especially in cases where Mycoplasma pneumoniae, Legionella species and Chlamydia pneumoniae are ruled out. In such cases, a correct anamnesis of the patient is basic to clarify which pathogens might have produced the infection. For this reason, health professionals including veterinarians and laboratory personnel working with zoonotic pathogens should keep their doctors informed. A human case of atypical pneumonia linked to Chlamydia abortus is reported. A 47-year-old male, a veterinarian researcher into chlamydiae, developed respiratory symptoms, breathing problems and high fever. Serological analyses ruled out the involvement of several respiratory pathogens, such as M. pneumoniae, Legionella pneumophila, Rickettsia conorii and C. pneumoniae, and Chlamydia abortus was identified as the possible aetiological agent of the infection. The isolation of C. abortus from the patient's sputum and subsequent molecular analysis confirmed the presence of this microorganism. As far as we know, although C. abortus has not been previously described as capable of causing pneumonia in humans, this is the first reported case of atypical pneumonia in which C. abortus is thought to have played an aetiological role.

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

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....

Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study.

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Hsing-Cheng Liu

Full Text Available This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients.A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147 were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association.We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27-10.64, p<0.05 and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40-6.24, p<0.001 were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20-3.44, p<0.01, there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis.Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy.

Risperidone, quetiapine, and olanzapine adjunctive treatments in major depression with psychotic features: a comparative study

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Gabriel A

2013-04-01

Full Text Available A Gabriel Departments of Psychiatry and Community Health Sciences, University of Calgary, Calgary, AB, Canada Objectives: The purpose of this study was to compare the effectiveness of novel antipsychotics in the treatment of psychotic depression. Method: Consecutive patients who were admitted (n = 51 with a confirmed diagnosis of major depression with psychotic features (delusions or hallucinations or both participated in this open-label, naturalistic study. All patients were treated with selective serotonin reuptake inhibitors (SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs (citalopram or venlafaxine extended release [XR], and atypical antipsychotic agents were added, as tolerated, during the first week of initiating the citalopram or venlafaxine. There were patients (n = 16 who received risperidone, who received quetiapine (n = 20, and who received olanzapine (n = 15, as an adjunctive treatment to either citalopram or venlafaxine for at least 8 weeks. Outcome measures included the Clinical Global Impression-Severity subscale (CGI-S, as the primary outcome measure, as well as the Hamilton Rating Scale for Depression-21 item (HAM-D21 and the Brief Psychiatric Rating Scale (BPRS. Tolerance to treatments and weight changes were monitored over the period of the trial. Results: All patients completed the trial with no drop outs. At 8 weeks, there was a statistically significant (P 0.01 in the olanzapine group. Conclusion: Quetiapine, risperidone, and olanzapine, given as adjunctive treatment with SSRIS or SNRIs can significantly and equally improve depressive and psychotic symptoms, in the short-term treatment of major depression with psychotic features. The author recommends that large controlled trials be conducted to examine the differences in long-term efficacy and tolerance between the atypical antipsychotic agents, in the treatment of major depression with or without psychotic features. Keywords: depression, novels

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.

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

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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

Cost-effectiveness Analysis of Antipsychotic Combination Therapy in Schizophrenia Inpatients

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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.

Neurological Adverse Effects of Antipsychotics in Children and Adolescents.

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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

Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

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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.

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

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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

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...

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:

Antipsychotic medication for early episode schizophrenia

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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

[Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

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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.

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

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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

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

[Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

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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.

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

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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

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

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.  ...

Metabolic Syndrome in Schizophrenia: A Non‑systematic Review

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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.

Metabolic Syndrome in Schizophrenia: A Non‑systematic Review

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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.

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...

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 ...

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.

Pancreatitis following Olanzapine Therapy: A Report of Three Cases

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Thomas A. Kerr

2007-06-01

Full Text Available Context: Atypical antipsychotic agents (clozapine, olanzapine have been linked to metabolic effects and acute pancreatitis. Case Report: We reviewed the inpatient and outpatient records of three patients who developed acute pancreatitis while being treated with olanzapine. The mean age of the patients was 37.7 years (range 18–54 years, 2 female, 1 male. No alternative cause of acute pancreatitis was found in two of the three patients. In the remaining patient, olanzapine may have contributed to acute pancreatitis in the setting of hypertriglyceridemia. Olanzapine was discontinued in all instances. Over a mean follow-up of 14 months, one patient has had a relapsing course, but the remaining two patients have been symptom free without recurrence of acute pancreatitis. Conclusions: Our case series adds further support to the potential link between olanzapine use and acute pancreatitis. Close monitoring of metabolic parameters is suggested in patients treated with olanzapine. Alternative antipsychotic agents should be considered in patients at high risk for pancreatitis.

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

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.

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

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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.

The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

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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

Antipsychotic Selection for Acute Agitation and Time to Repeat Use in a Psychiatric Emergency Department.

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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.

Extrastriatal dopamine D-2/3 receptors and cortical grey matter volumes in antipsychotic-naive schizophrenia patients before and after initial antipsychotic treatment

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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...

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

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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

Acute Antipsychotic Treatment of Children and Adolescents With Schizophrenia-Spectrum Disorders

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Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, Dorte

2017-01-01

. Serious adverse events, discontinuation of treatment, sedation, insomnia, or change in triglycerides did not differ among antipsychotics. CONCLUSION: This network meta-analysis showed comparable efficacy among antipsychotics for early-onset schizophrenia, except that efficacy appeared inferior...

Frequency and correlates of anticholinergic use among patients with schizophrenia in Denmark

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Pristed, S G; Correll, C U; Nielsen, Jimmi

2017-01-01

Anticholinergic medications are used to treat extrapyramidal adverse effects induced by antipsychotics. Anticholinergics are associated with adverse effects: constipation, dry mouth and worsening of cognitive function. Anticholinergics have potential for abuse and are not recommended for long term...... Region. Long-term use of anticholinergics was predicted by older age, age at debut of schizophrenia, receiving early retirement pension, typical antipsychotic use, antipsychotic polypharmacy, typical + atypical antipsychotics, antidepressant treatment, high doses of antipsychotics measured in defined...

Could Reward-disturbances caused by antipsychotic medication lead to weight gain?

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Nielsen, Mette Ødegaard; Rostrup, Egill; Nørbak-Emig, Henrik

2014-01-01

BACKGROUND The reward system is known to be central to the regulation of appetite. Further, disturbances of the brain reward system are suggested to play an important role in the development of central psychopathological symptoms in schizophrenia. Antipsychotic medication partly acts by modulating...... the reward system and most antipsychotics cause some degree of weight gain. Recently, a relation between weight gain caused by one week of olanzapine treatment and change in reward signalling was found in healthy volunteers1. To our knowledge there are no previous studies examining how the effect...... of antipsychotic treatment on the reward system relate to weight gain in patients. METHODS 50 antipsychotic-naïve first-episode patients with schizophrenia and 40 healthy controls were included in the study at baseline. 38 patients and 31 healthy controls were re-examined after six weeks where patients were...

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...

Safety evaluation of zotepine for the treatment of schizophrenia.

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Riedel, Michael; Musil, Richard; Seemüller, Florian; Spellmann, Ilja; Möller, Hans-Jürgen; Schennach-Wolff, Rebecca

2010-07-01

Atypical antipsychotics have become the first-line treatment for patients suffering from schizophrenia in the industrialized world. Given the frequent necessity of a life-long enduring antipsychotic treatment, the compounds' safety profile is of great importance for patients and caregivers. Zotepine is an antipsychotic with atypical properties and previous data have suggested a very favorable side effect profile. The aim of this review is to provide a broad knowledge base on the safety profile of zotepine deriving from currently available research results published in English medical databases. The focus of this research reports starts in the 1990s with zotepine's approval in Europe. This paper incorporates data on placebo-controlled studies of zotepine as well as studies with comparator compounds also beyond the diagnostic boarder of schizophrenia regarding zotepine's safety. The take home message of this safety evaluation of zotepine is that compared to typical compounds zotepine induces less extrapyramidal side effects; however, in terms of comparing zotepine's safety with other atypical antipsychotics more studies are needed to draw final conclusions.

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

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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.

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

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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.

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

Antipsychotic Medication Prescription Patterns in Adults with Developmental Disabilities Who Have Experienced Psychiatric Crisis

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Lunsky, Yona; Elserafi, Jonny

2012-01-01

Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…

Emerging role of sertindole in the management of schizophrenia

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Stephanie L Cincotta

2010-07-01

Full Text Available Stephanie L Cincotta1, Joshua S Rodefer21Georgetown University School of Medicine, Washington DC, USA; 2Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida, USAAbstract: The atypical antipsychotic sertindole is a phenylindole-derived compound that has affinity for and functions as an antagonist at a number of receptor systems, including dopamine D2 receptors, 5-HT2A and 5-HT2C receptors, and a-1-noradrenergic receptors. Although previous data suggested that sertindole was well tolerated and had good efficacy against both positive and negative symptom clusters, reports of QT prolongation with sertindole prompted its voluntary removal from the market in 1998. After further safety analyses, it recently regained approval and was reintroduced to the European market for the treatment of schizophrenia, where its role in therapy among available atypicals remains unclear. This article evaluates the preclinical and clinical data regarding sertindole’s effectiveness and concludes that sertindole continues to demonstrate a number of strengths, including effective management of both positive and negative symptoms, well-tolerated side effects (including little or no sedation, weight gain, and extrapyramidal side effects, and a superior procognitive profile that is unique among atypical antipsychotics. However, minor concerns regarding its sexual side effects and the major consideration of QT prolongation suggest that additional comparative effectiveness studies are needed to determine the superiority of sertindole vs other atypical antipsychotics recently introduced.Keywords: atypical, antipsychotic, cognition, psychosis, 5-HT2, 5-HT6

Successful Management of Psychotropics Induced Stuttering Priapism with Pseudoephedrine in a Patient with Schizophrenia.

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Thippaiah, Srinagesh Mannekote; Nagaraja, Soumya; Birur, Badari; Pandurangi, Ananda

2018-02-05

Stuttering Priapism is a recurrent, persistent penile erection in the absence of sexual desire due to altered genital hemodynamics, affecting the arterial component (high flow, non-ischemic) or the veno-occlusive mechanism (low flow, ischemic). Both typical and atypical antipsychotics increase the risk for priapism with greater implications in typicals than atypicals. Prompt recognition and treatment are important as 40% to 50% of patients with stuttering priapism may develop an erectile dysfunction if left untreated. There are several case reports in the literature about the association between psychotropic agents and priapism. However, there are no reports of successfully treating stuttering priapism using pseudoephedrine (sudafed) in the adult population. Here we present successful management of psychotropics induced stuttering priapism with pseudoephedrine in a male patient with schizophrenia.

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

Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

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Hu, Kai-Fang; Chou, Yu-Hsiang; Wen, Yen-Hsia; Hsieh, Kun-Pin; Tsai, Jui-Hsiu; Yang, Pinchen; Yang, Yi-Hsin; Lin, Chun-Hung Richard

2016-11-30

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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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.

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

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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.

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

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... 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 ...

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

OpenAIRE

Reeves, Gloria M; Keeton, Courtney; Correll, Christoph U; Johnson, Jacqueline L; Hamer, Robert M; Sikich, Linmarie; Hazzard, Lindsey; Alderman, Cheryl; Scheer, Abigail; Mabe, Micah; Kapoor, Sandeep; Sheridan, Eva; Borner, Irmgard; Bussell, Kristin; Pirmohamed, Sara

2013-01-01

Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) stu...

Update on quetiapine in the treatment of bipolar disorder: results from the BOLDER studies

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Prashant Gajwani

2007-01-01

Full Text Available Prashant Gajwani1, David J Muzina2, David E Kemp3, Keming Gao1, Joseph R Calabrese11Case Western Reserve University (CWRU School of Medicine, 2Cleveland Clinic Lerner College of Medicine of CWRU, 3Case Western Reserve University, Cleveland OH, USAAbstract: The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same.Keywords: bipolar disorder, quetiapine, BOLDER studies

Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

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Ludovic Samalin

2016-11-01

Full Text Available The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg. Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs, and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

Aripiprazole-associated tic in a schizophrenia patient

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Guo X

2015-03-01

Full Text Available Xieli Guo,1,2,* Dali Lu,3,* Yugang Jiang1 1Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Neurosurgery, Jinjiang Hospital of Quanzhou Medical College, Jinjiang, Fujian, People’s Republic of China; 3Department of Psychiatry, Xiamen Xianyue Hospital, Xiamen, Fujian, People’s Republic of China *These authors contributed equally to this work Abstract: Tic disorder, characterized by the presence of both motor and vocal tics is common in adolescents and adults. Antipsychotics including typical antipsychotics and atypical antipsychotics are generally recognized by experts as the most effective pharmacological treatment for tics. However, previous studies suggest that tic-like symptoms might manifest during treatment with atypical antipsychotics such as clo­zapine, quetiapine, but not aripiprazole. We present the first case, to our knowledge, of an adult schizophrenia patient who developed tics during treatment with aripiprazole. Keywords: aripiprazole, antipsychotics, tic, schizophrenia, side effect

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

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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…

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

Lean Methodology Reduces Inappropriate Use of Antipsychotics for Agitation at a Psychiatric Hospital.

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Goga, Joshana K; Depaolo, Antonio; Khushalani, Sunil; Walters, J Ken; Roca, Robert; Zisselman, Marc; Borleis, Christopher

2017-01-01

To Evaluate the Effects of Applying Lean Methodology-Improving Quality Increasing Efficiency by Eliminating Waste and Reducing Costs-An Approach To Decrease the Prescribing Frequency of Antipsychotics for The Indication of Agitation. Historically Controlled Study. Bheppard Pratt Health System is the Largest Private Provider of Psychiatric Care in Maryland With a Total Bed Capacity of 300. There Were 4 337 Patient Days From November 1 2012 to October 31 2013 on the Dementia Unit. All Patients Admitted on the Dementia Unit Were 65 Years of Age and Older with a Primary Diagnosis of Dementia. our Multidisciplinary Team Used Lean Methodology to Identify the Root Causes and Interventions Necessary to Reduce Inappropriate Antipsychotic Use. The Primary Outcome Was Rate of Inappropriately Indicating Agitation as the Rationale When Prescribing Antipsychotic Medications. There Was a 90% (P Agitation. The Lean Methodology Interventions Led To A 90% (P Agitation and a 10% Rate Reduction in Overall Antipsychotic Prescribing. Key Words: Agitation Alzheimer's Antipsychotics Behavioral and Psychological Symptoms of Dementia Centers For Medicare & Medicaid Services Dementia Root-cause Analysis. BPSD = Behavioral and Psychological Symptoms of Dementia CATIE-AD = Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease EMR = Electronic Medical Records GAO = Government Accountability Office GNCIS = Geriatric Neuropsychiatric Clinical Indicator Scale.

A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality.

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Sahin, Aynur; Cicek, Mustafa; Gonenc Cekic, Ozgen; Gunaydin, Mucahit; Aykut, Demet Saglam; Tatli, Ozgur; Karaca, Yunus; Arici, Mualla Aylin

2017-12-01

Neuroleptic malignant syndrome (NMS) is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. The mean age of the 18 patients diagnosed with NMS was 46.9 ± 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN), creatine kinase (CK) and mean platelet volume (MPV) values (p ≤ 0.05). In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS.

Olanzapine-induced ischemic colitis

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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.

Aripiprazole in pediatric psychosis and bipolar disorder: a clinical review.

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Doey, Tamison

2012-01-01

Aripiprazole is an atypical antipsychotic with unique pharmacological properties, used for a variety of indications, including psychotic and mood disorders in youth. Existing literature was reviewed to summarize experience with this agent in that population. A review of relevant literature using the key words aripiprazole, children, pediatric, all child, schizophrenia, bipolar disorder, and atypical antipsychotics was conducted. A total of 140 articles and book chapters were identified, of which 7 reported double-blind controlled trials with aripiprazole, 5 were meta-analyses of pooled data, 11 were open label trials, 10 were chart reviews, and 17 were case reports or case series. Although every effort was made to locate all available data, some information from posters or researchers was not available. Publication bias tends to report positive outcomes with a treatment, while negative studies are less likely to be reported. Most trials are of short duration. Treatment with aripiprazole is associated with significant reduction of the Positive and Negative Symptom Scale (PANSS) scores in youth with schizophrenia, and reductions in items in the negative symptom scores at higher doses (30 mg/day). Significant reductions in the Young Mania Rating Scale (YMRS) have been demonstrated in youth with bipolar disorder. In mixed populations, reductions in the Clinical Global Impressions Scale (CGI-S) have also been demonstrated when compared with treatment with placebo. Head-to-head comparisons are fewer in number, and overall aripiprazole compares favorably with other atypical antipsychotics (ATAs) in the populations studied. Treatment with aripiprazole is reported to have a lower incidence of weight gain, and less elevation of prolactin. At higher doses, it appears more likely to result in extrapyramidal symptoms (EPS) and tremor. Copyright © 2012. Published by Elsevier B.V.

The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey

DEFF Research Database (Denmark)

Deurell, Maria; Weischer, Merete; Pagsberg, Anne Katrine

2008-01-01

for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244......The number of children and adolescents with psychiatric disorders being treated with antipsychotic medication is increasing significantly; however, only a limited evidence-base is available on this topic, especially when children are concerned. This study reports and discusses the use...... patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail....

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

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain

DEFF Research Database (Denmark)

Ebdrup, Bjørn H; Knop, Filip K; Ishøy, Pelle L

2012-01-01

between schizophrenia and overweight patients. DISCUSSION: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogues used in the treatment of type 2 diabetes are associated with significant and sustained weight loss...... are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes...... in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogues are discussed. CONCLUSIONS: We propose that adjunctive treatment with GLP-1 analogues may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies...

[Lithium and anticonvulsants in the treatment of mania and in the prophylaxis of recurrences].

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Salvi, Virginio; Cat Berro, Alberto; Bechon, Elisa; Bogetto, Filippo; Maina, Giuseppe

2011-01-01

A mood stabilizer is an agent effective in treating both poles of the illness and at the same time being able to prevent both manic and depressive episodes in bipolar disorder. According to a broader definition, a mood stabilizer should be effective in decreasing the frequency or severity of any type of episode in bipolar disorder, without worsening the frequency or severity of episodes of opposite polarity. According to this, anticonvulsants and atypical antipsychotics can be considered as mood stabilizers. In this paper we review the use of lithium and other anticonvulsants that have proved effective in randomized controlled trials of the treatment of manic episodes and prevention of recurrences of bipolar disorder. Lithium and valproate are considered as first-line treatment options for acute mania while evidence regarding carbamazepine is insufficient to consider it as a first-line agent. Patients who fail to respond to first-line treatments may benefit from the adjunct of an atypical antipsychotic such as olanzapine, quetiapine, risperidone or aripiprazole. Lithium retains the strongest evidence of efficacy in the prophylaxis of manic episodes, lamotrigine in the prevention of depressive episodes. Valproate and carbamazepine have no indication for long-term treatment of bipolar disorder. Lithium can still be considered a gold standard in the treatment of manic episodes as well as in the prophylaxis of recurrences. Other anticonvulsants should be employed in particular situations, such as valproic acid in the treatment of mania and lamotrigine in the prevention of depressive recurrences.

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

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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.

Olanzapine-Induced Neuroleptic Malignant Syndrome

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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.

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

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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.

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

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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

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

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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.

Time course of lung function changes in atypical pneumonia.

Science.gov (United States)

Benusiglio, L N; Stalder, H; Junod, A F

1980-01-01

We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825

A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia.

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Harrow, Martin; Jobe, Thomas H; Faull, Robert N; Yang, Jie

2017-10-01

To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multifollowup research on 139 initially psychotic patients. The 70 patients with schizophrenia and 69 initially psychotic mood disordered control patients were followed up 6 times over 20 years. We compared the influence on work functioning of patients with schizophrenia continuously prescribed antipsychotics with patients with schizophrenia not prescribed antipsychotics, using statistical controls for inter-subject differences. While antipsychotics reduce or eliminate flagrant psychosis for most patients with schizophrenia at acute hospitalizations, four years later and continually until the 20 year followups, patients with schizophrenia not prescribed antipsychotics had significantly better work functioning. The work performance of the patients who were continuously prescribed antipsychotics was at a low rate and did not improve over time. Multiple other factors also interfere with work functioning. The data suggest that some patients with schizophrenia not prescribed antipsychotics for prolonged periods can function relatively well. Multiple other factors are associated with poor post-hospital work performance. The longitudinal data raise questions about prolonged treatment of schizophrenia with antipsychotic medications. Copyright © 2017 Elsevier B.V. All rights reserved.

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 ...

Role of 5-HT2C receptor gene variants in antipsychotic-induced weight gain

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Brandl EJ

2011-08-01

Full Text Available Tessa JM Wallace, Clement C Zai, Eva J Brandl, Daniel J MüllerNeurogenetics Section, Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, CanadaAbstract: Antipsychotic-induced weight gain is a serious side effect of antipsychotic medication that can lead to increased morbidity, mortality, and non-compliance in patients. Numerous single nucleotide polymorphisms have been studied for association with antipsychotic-induced weight gain in an attempt to find genetic predictors of this side effect. An ability to predict this side effect could lead to personalized treatment plans for predisposed individuals, which could significantly decrease the prevalence and severity of weight gain. Variations in the serotonin receptor 2c gene (HTR2C have emerged as promising candidates for prediction of antipsychotic-induced weight gain. Specifically, the well-studied -759C/T promoter polymorphism has been associated with weight gain in diverse populations, although some studies have reported no association. This discrepancy is likely due to heterogeneity in study design with respect to ethnicity, treatment duration, and other variables. Notably, the association between HTR2C and antipsychotic-induced weight gain appears strongest in short-term studies on patients with limited or no previous antipsychotic treatment. Other, less extensively studied promoter polymorphisms (-697C/G, -997G/A, and -1165A/G have also emerged as potential predictors of antipsychotic-induced weight gain. Conversely, the well-studied intronic polymorphism Cys23Ser does not appear to be associated. With further research on both HTR2C and other genetic and environmental predictors of antipsychotic-induced weight gain, a predictive test could one day be created to screen patients and provide preventative or alternative treatment for those who are predisposed to this serious side effect.Keywords: HTR2C, pharmacogenomics, promoter polymorphism

Antipsychotics and dementia in Canada: a retrospective cross-sectional study of four health sectors.

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Rios, Sebastian; Perlman, Christopher M; Costa, Andrew; Heckman, George; Hirdes, John P; Mitchell, Lori

2017-10-23

Antipsychotic medications are not recommended for the management of symptoms of dementia, particularly among persons with no behavioral or psychological symptoms. We examine patterns of antipsychotic medication use among persons with dementia across health sectors in Canada, with a focus on factors related to use among those without behavioral or psychotic symptoms. Using a retrospective cross-sectional design, this study examines antipsychotic use among adults aged 65 or older with dementia in home care (HC), complex continuing care (CCC), long-term care (LTC), and among alternate level care patients in acute hospitals (ALC). Using clinical data from January 1, 2009 to December 31, 2014, the prevalence of antipsychotic medication use was estimated by the presence of behavioral and psychotic symptoms. Logistic regression was used to identify sector specific factors associated with antipsychotic use in the absence of behavioral and psychotic symptoms. The total prevalence of antipsychotic use among older adults with dementia was 26% in HC, 54% in ALC, 41% in CCC, and 48% in LTC. This prevalence ranged from 38% (HC) to 73% (ALC) for those with both behavioral and psychotic symptoms and from 15% (HC) to 31% (ALC) among those with no symptoms. The regression models identified a number of variables were related to antipsychotic use in the absence of behavior or psychotic symptoms, such as bipolar disorder (OR = 6.63 in CCC; OR = 5.52 in LTC), anxious complaints (OR = 1.54 in LTC to 2.01 in CCC), and wandering (OR = 1.83 in ALC). Potentially inappropriate use of antipsychotic medications is prevalent among older adults with dementia across health sectors. The variations in prevalence observed from community to facility based care suggests that system issues may exist in appropriately managing persons with dementia.

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.

ANTIPSYCHOTICS REVERSE P-GLYCOPROTEIN-MEDIATED DOXORUBICIN RESISTANCE IN HUMAN UTERINE SARCOMA MES-SA/Dx5 CELLS: A NOVEL APPROACH TO CANCER CHEMOTHERAPY.

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Angelini, A; Ciofani, G; Conti, P

2015-01-01

Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains one of the major obstacles to effective cancer chemotherapy. Several chemosensitizers have been used in vivo and in vitro to reverse MDR but have exhibited several unwanted side effects. Antipsychotics are often administered to treat psychiatric disorders such as delirium, anxiety and sleep disorders in cancer patients during chemotherapy. The present in vitro study, examined the effects of two common antipsychotic compounds, haloperidol and risperidone, and a natural compound such as theobromine on reversing MDR Pgp-mediated, to evaluate their potential use as chemosensitizing agents. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp (100-fold), were treated with the antipsychotic alone (1, 10 and 20 μM) or in combination with different concentrations of doxo (2, 4 and 8 μM). The accumulation and cytotoxicity of doxo (MTT assay) and cellular GSH content (GSH assay) in comparison with verapamil, a well-known Pgp inhibitor, used as reference molecule were examined. It was found that the three compounds significantly enhanced the intracellular accumulation of doxo in resistant cancer cells, when compared with cells receiving doxo alone (p 30%) in resistant cells, when compared to untreated control cells (ptheobromine showed to be an effective Pgp inhibitor with the lowest toxicity.

Pharmacogenetics and outcome with antipsychotic drugs.

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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.

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

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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.

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.

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

Science.gov (United States)

2012-01-01

Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. PMID:22891821

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

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Ebdrup Bjørn H

2012-08-01

Full Text Available Abstract Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1. Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted.

Emerging role of aripiprazole for treatment of irritability associated with autistic disorder in children and adolescents.

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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.

Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?

DEFF Research Database (Denmark)

Murray, Robin M; Quattrone, Diego; Natesan, Sridhar

2016-01-01

over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss...... of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should...

Isolation of Chlamydia abortus from a laboratory worker diagnosed with atypical pneumonia

OpenAIRE

Ortega, Nieves; Caro, M. Rosa; Gallego, M. Carmen; Murcia-Belmonte, Antonio; ?lvarez, Daniel; del R?o, Laura; Cuello, Francisco; Buend?a, Antonio J.; Salinas, Jes?s

2016-01-01

Background Identifying the aetiological agent of atypical pneumonia in human can sometimes be a tedious process, especially in cases where Mycoplasma pneumoniae, Legionella species and Chlamydia pneumoniae are ruled out. In such cases, a correct anamnesis of the patient is basic to clarify which pathogens might have produced the infection. For this reason, health professionals including veterinarians and laboratory personnel working with zoonotic pathogens should keep their doctors informed. ...

Biases in medication prescribing: the case of second-generation antipsychotics.

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Makhinson, Michael

2010-01-01

The shift from first-generation antipsychotic medications to second-generation antipsychotic medications initially caused a wave of excitement about the potential for improved and broader efficacy of these medications concurrent with an improved side-effect profile. Recent data from high-quality research analyses have subsequently raised significant questions about these claims. This research evidence has, however, not altered prescribing behavior in a way that would be expected from fully rational evaluation of the evidence. Prescribing decisions represent poorly understood, complex behaviors influenced by a number of external and internal forces, some of which may be elucidated by advances in social and cognitive psychology. In this article, the decision to prescribe first- versus second-generation antipsychotic medications is examined, and specific social psychological biases and individual cognitive biases are hypothesized to be significant influences on clinicians. These biases may perpetuate disparity between research evidence and clinical practice.

Atypical idiopathic inflammatory demyelinating lesions

DEFF Research Database (Denmark)

Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

2013-01-01

Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class......Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can...... be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical...

Paliperidone extended-release: does it have a place in antipsychotic therapy?

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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

Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

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Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

2010-01-01

Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence

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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.

Antipsychotics for fibromyalgia in adults.

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Walitt, Brian; Klose, Petra; Üçeyler, Nurcan; Phillips, Tudor; Häuser, Winfried

2016-06-02

quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included a total of four studies with 296 participants.Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety).Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low

Antipsychotic treatment in schizophrenia: the role of computerized neuropsychological assessment.

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Kertzman, Semion; Reznik, Ilya; Grinspan, Haim; Weizman, Abraham; Kotler, Moshe

2008-01-01

The present study analyzes the role of neurocognitive assessment instruments in the detection of the contribution of antipsychotic treatment to cognitive functioning. Recently, a panel of experts suggested six main domains (working memory; attention/vigilance; verbal/visual learning and memory; reasoning and problem solving; speed of processing) implicated in schizophrenia-related cognitive deficits, which serve as a theoretical base for creation of real-time computerized neurocognitive batteries. The high sensitivity of computerized neuropsychological testing is based on their ability to adopt the reaction time (RT) paradigm for the assessment of brain function in a real-time regime. This testing is highly relevant for the monitoring of the cognitive effects of antipsychotics. Computerized assessment assists in the identification of state- and trait-related cognitive impairments. The optimal real-time computerized neurocognitive battery should composite balance between broad and narrow coverage of cognitive domains relevant to the beneficial effects of antipsychotics and will enable better planning of treatment and rehabilitation programs.

Paralytic ileus requiring hospitalization secondary to high-dose antipsychotic polypharmacy and benztropine.

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Kwiatkowski, Mercedes; Denka, Zachary D; White, Christopher C

2011-01-01

Ileus can result from the combined activity of antipsychotic and anticholinergic medications. Despite frequent use, case reports in the literature are sparse. We present a patient who developed a paralytic ileus requiring extended hospitalization. Providers should minimize antipsychotic and concurrent anticholinergic medications, consider prophylactic bowel regimens and monitor for constipation. Copyright © 2011 Elsevier Inc. All rights reserved.

A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality

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Aynur Sahin

2017-12-01

Full Text Available Objective: Neuroleptic malignant syndrome (NMS is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. Material and methods: This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. Results: The mean age of the 18 patients diagnosed with NMS was 46.9 ± 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN, creatine kinase (CK and mean platelet volume (MPV values (p ≤ 0.05. Conclusion: In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS.

Curcumin Mitigates the Intracellular Lipid Deposit Induced by Antipsychotics In Vitro.

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Alberto Canfrán-Duque

Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychotic-induced intracellular lipid accumulation.HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation.Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics.Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials.

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

Focus on risperidone.

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Green, B

2000-01-01

Risperidone is a relatively new antipsychotic available world-wide since the early 1990s. It has been characterised as atypical, but shares some of the extrapyramidal side-effect profile of the earlier antipsychotics, when used at doses higher than those recommended by the manufacturer (4-6 mg/day). There is now adequate comparison with conventional antipsychotics to suggest its superiority, but a depot formulation is needed to complete the picture.

Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis.

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Vermeulen, J; van Rooijen, G; Doedens, P; Numminen, E; van Tricht, M; de Haan, L

2017-10-01

Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.

Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update

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Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Jun, Tae-Youn; Patkar, Ashwin A; Masand, Prakash S

2016-01-01

Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013. PMID:27689026

A brief version of the Subjects' Response to Antipsychotics questionnaire to evaluate treatment effects

NARCIS (Netherlands)

Lako, Irene M.; Bruggeman, Richard; Liemburg, Edith J.; van den Heuvel, Edwin R.; Knegtering, Henderikus; Slooff, Cees J.; Wiersma, Durk; Taxis, Katja

Background: Monitoring patients' experiences with antipsychotics may help to improve medication adherence and outcome. We aimed to develop a shorter version of a comprehensive 74-item self-report questionnaire suitable for routine monitoring of desired and undesired effects of antipsychotics.

Antipsychotic Polypharmacy in a Treatment-Refractory Schizophrenia Population Receiving Adjunctive Treatment With Electroconvulsive Therapy

DEFF Research Database (Denmark)

Kristensen, Diana; Hageman, Ida; Bauer, Jeanett

2013-01-01

Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT).......Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT)....

Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism

NARCIS (Netherlands)

van Nimwegen, Lonneke J. M.; Storosum, Jitschak G.; Blumer, Regje M. E.; Allick, Gideon; Venema, Henk W.; de Haan, Lieuwe; Becker, Hiske; van Amelsvoort, Therese; Ackermans, Mariette T.; Fliers, Eric; Serlie, Mireille J. M.; Sauerwein, Hans P.

2008-01-01

OBJECTIVE: Our objective was to measure insulin sensitivity and body composition in antipsychotic-naive patients with DSM IV schizophrenia and/or schizoaffective disorder compared with matched controls. DESIGN: Seven antipsychotic medication-naive patients fulfilling the DSM IV A criteria for

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

OBJECTIVE: To evaluate the effect of a multifaceted educational intervention on the frequency of antipsychotic co-prescribing in adult schizophrenia out-patients. METHOD: Controlled quasi-experimental study performed in two Danish municipalities matched for baseline prevalence of antipsychotic po...... for differences in case-mix (P = 0.07). CONCLUSION: This multifaceted educational intervention failed to reduce the frequency of antipsychotic co-prescribing, but it suggested that future efforts to improve prescribing practice should address organizational barriers to implementation....

Understanding the Uncanny: Both Atypical Features and Category Ambiguity Provoke Aversion toward Humanlike Robots.

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Strait, Megan K; Floerke, Victoria A; Ju, Wendy; Maddox, Keith; Remedios, Jessica D; Jung, Malte F; Urry, Heather L

2017-01-01

Robots intended for social contexts are often designed with explicit humanlike attributes in order to facilitate their reception by (and communication with) people. However, observation of an "uncanny valley"-a phenomenon in which highly humanlike entities provoke aversion in human observers-has lead some to caution against this practice. Both of these contrasting perspectives on the anthropomorphic design of social robots find some support in empirical investigations to date. Yet, owing to outstanding empirical limitations and theoretical disputes, the uncanny valley and its implications for human-robot interaction remains poorly understood. We thus explored the relationship between human similarity and people's aversion toward humanlike robots via manipulation of the agents' appearances. To that end, we employed a picture-viewing task ( N agents = 60) to conduct an experimental test ( N participants = 72) of the uncanny valley's existence and the visual features that cause certain humanlike robots to be unnerving. Across the levels of human similarity, we further manipulated agent appearance on two dimensions, typicality (prototypic, atypical, and ambiguous) and agent identity (robot, person), and measured participants' aversion using both subjective and behavioral indices. Our findings were as follows: (1) Further substantiating its existence, the data show a clear and consistent uncanny valley in the current design space of humanoid robots. (2) Both category ambiguity, and more so, atypicalities provoke aversive responding, thus shedding light on the visual factors that drive people's discomfort. (3) Use of the Negative Attitudes toward Robots Scale did not reveal any significant relationships between people's pre-existing attitudes toward humanlike robots and their aversive responding-suggesting positive exposure and/or additional experience with robots is unlikely to affect the occurrence of an uncanny valley effect in humanoid robotics. This work furthers

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...

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

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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.

Novel antipsychotics in bipolar and schizoaffective mania

NARCIS (Netherlands)

Slooff, CJ

Objective: Novel antipsychotics are increasingly used in the treatment of bipolar and schizoaffective mania. This paper presents an overview of the controlled studies in this field. Method: Using cross-references, a computerized search was performed on MEDLINE and EMBASE psychiatry covering the

Non-adherence to antipsychotic medication, relapse and rehospitalisation in recent-onset schizophrenia

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Widen Jan H

2008-04-01

Full Text Available Abstract Background The aims of this study were to describe outcome with respect to persistent psychotic symptoms, relapse of positive symptoms, hospital admissions, and application of treatment by coercion among patients with recent onset schizophrenia being adherent and non-adherent to anti-psychotic medication. Materials and methods The study included 50 patients with recent onset schizophrenia, schizoaffective or schizophreniform disorders. The patients were clinically stable at study entry and had less than 2 years duration of psychotic symptoms. Good adherence to antipsychotic medication was defined as less than one month without medication. Outcomes for poor and good adherence were compared over a 24-month follow-up period. Results The Odds Ratio (OR of having a psychotic relapse was 10.27 and the OR of being admitted to hospital was 4.00 among non-adherent patients. Use of depot-antipsychotics were associated with relapses (OR = 6.44. Conclusion Non-adherence was associated with relapse, hospital admission and having persistent psychotic symptoms. Interventions to increase adherence are needed. Trial registration Current Controlled Trials NCT00184509. Key words: Adherence, schizophrenia, antipsychotic medication, admittances, relapse.

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

Diabetes mellitus contributes to excessive cardiovascular deaths and reduced life expectancy in schizophrenia. This population-based cohort study investigated the endogenous risk for diabetes in antipsychotic-naive schizophrenia and evaluated the risks added by starting antipsychotic treatment in people with schizophrenia. The study followed all people born in Denmark on or after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data on prescriptions of antipsychotics. Diabetes was ascertained from the Danish National Patient Register and Danish National Prescription Registry. The authors estimated the endogenous and antipsychotic-related risks for diabetes by using Cox proportional hazards regression models, while accounting for potential confounders. Of the cohort members, 14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years). The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71-5.41) in antipsychotic-naive schizophrenia compared with the general population. The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95-6.82) than the risk in antipsychotic-naive schizophrenia, after adjustment for family history of diabetes and other potential confounders. First-line treatment with either first-generation antipsychotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited to type 2 diabetes corroborated these results. Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics

Determinants of the nurses' and nursing assistants' request for antipsychotics for people with dementia

NARCIS (Netherlands)

Janus, Sarah I M; van Manen, Jeannette G; IJzerman, Maarten J; Bisseling, Marloes; Drossaert, Constance H C; Zuidema, Sytse U

Background: Although physicians are responsible for writing the antipsychotic prescriptions for patients with dementia, the initiative is often taken by nurses or nursing assistants. To reduce antipsychotics uses, one needs to understand the reasons for nurses and nursing assistants to request them.

Determinants of the nurses’ and nursing assistants’ request for antipsychotics for people with dementia

NARCIS (Netherlands)

Janus, Sarah; van Manen, Jeanette Gabrielle; IJzerman, Maarten Joost; Bisseling, Marloes; Drossaert, Constance H.C.; Zuidema, Sytse U.

2017-01-01

Although physicians are responsible for writing the antipsychotic prescriptions for patients with dementia, the initiative is often taken by nurses or nursing assistants. To reduce antipsychotics uses, one needs to understand the reasons for nurses and nursing assistants to request them. This study

Predictive validity of proposed remission criteria in first-episode schizophrenic patients responding to antipsychotics

NARCIS (Netherlands)

Wunderink, Lex; Nienhuis, Fokko J.; Sytema, Sjoerd; Wiersma, Durk

The objective of this study was to examine the predictive validity of the remission criteria proposed by Andreasen et all in first-episode patients responding to antipsychotics. Antipsychotic responsive patients with first-episode schizophrenia showing symptom remission (n = 60) were compared with

Identifying fallacious arguments in a qualitative study of antipsychotic prescribing in dementia.

Science.gov (United States)

Donyai, Parastou

2017-10-01

Dementia can result in cognitive, noncognitive and behavioural symptoms which are difficult to manage. Formal guidelines for the care and management of dementia in the UK state that antipsychotics should only be prescribed where fully justified. This is because inappropriate use, particularly problematic in care-home settings, can produce severe side effects including death. The aim of this study was to explore the use of fallacious arguments in professionals' deliberations about antipsychotic prescribing in dementia in care-home settings. Fallacious arguments have the potential to become unremarkable discourses that construct and validate practices which are counter to guidelines. This qualitative study involved interviews with 28 care-home managers and health professionals involved in caring for patients with dementia. Potentially fallacious arguments were identified using qualitative content analysis and a coding framework constructed from existing explanatory models of fallacious reasoning. Fallacious arguments were identified in a range of explanations and reasons that participants gave for in answer to questions about initiating, reducing doses of and stopping antipsychotics in dementia. The dominant fallacy was false dichotomy. Appeal to popularity, tradition, consequence, emotion, or fear, and the slippery slope argument was also identified. Fallacious arguments were often formulated to present convincing cases whereby prescribing antipsychotics or maintaining existing doses (versus not starting medication or reducing the dose, for example) appeared as the only acceptable decision but this is not always the case. The findings could help health professionals to recognise and mitigate the effect of logic-based errors in decisions about the prescribing of antipsychotics in dementia. © 2016 Royal Pharmaceutical Society.

Perianal atypical leiomyoma: A case report.

Science.gov (United States)

Sun, Pingliang; Ou, Hailing; Huang, Shen; Wei, Longxiang; Zhang, Sen; Liu, Jiali; Geng, Shuguang; Yang, Kun

2017-12-01

Reports on perianal atypical leiomyoma, a perianal tumor, are rare. We confirmed a perianal atypical leiomyoma by its clinical presentation, magnetic resonance imaging findings, and immunohistochemistry. A 28-year-old female with a perianal mass found more than 4 years ago. The 5cm_4cm_4cm sized mass was located on the left side of the anus and vagina; The magnetic resonance imaging (MRI) scan revealed: A 4.1cm × 5.2cm × 4.9cm sized round mass was observed on the left side of the circumference. Perianal atypical leiomyoma. anal peripheral mass resection was performed under lumbar anesthesia. The postoperative course was uneventful, healing, the patient was discharged. Perianal atypical leiomyomas are benign tumors, but with the clinically atypical leiomyoma, it is sometimes difficult to distinguish between potential malignant smooth muscle tumors,and there may be malignant changes. Surgery should ensure complete resection, and to avoid postoperative recurrence, there should be a regular follow-up.

Prevalence of the metabolic syndrome in Danish psychiatric outpatients treated with antipsychotics

DEFF Research Database (Denmark)

Krane-Gartiser, Karoline; Breum, Leif; Glümrr, Charlotte

2011-01-01

The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment.......The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment....

Renal Failure in Dementia with Lewy Bodies Presenting as Catatonia

Science.gov (United States)

Fekete, Robert

2013-01-01

Catatonia, originally described by Karl Kahlbaum in 1874, may be regarded as a set of clinical features found in a subtype of schizophrenia, but the syndrome may also stem from organic causes including vascular parkinsonism, brain masses, globus pallidus lesions, metabolic derangements, and pharmacologic agents, especially first generation antipsychotics. Catatonia may include paratonia, waxy flexibility (cerea flexibilitas), stupor, mutism, echolalia, and catalepsy (abnormal posturing). A case of catatonia as a result of acute renal failure in a patient with dementia with Lewy bodies is described. This patient recovered after intravenous fluid administration and reinstitution of the atypical dopamine receptor blocking agent quetiapine, but benzodiazepines and amantadine are additional possible treatments. Recognition of organic causes of catatonia leads to timely treatment and resolution of the syndrome. PMID:23466522

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

Full Text Available Martha Sajatovic,1 Faith DiBiasi,2 Susan N Legacy3 1Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 2US Medical Affairs, Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA; 3US Medical Affairs, Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA Introduction: Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their real-world use remains limited. Understanding attitudes toward these medications may help identify barriers and inform personalized therapy. This literature review evaluated patient and clinician attitudes toward the use of antipsychotics for treating bipolar disorder. Materials and methods: A systematic search of the Cochrane Library, Ovid MEDLINE, Embase, and BIOSIS Previews identified English language articles published between January 1, 2000, and June 15, 2016, that reported attitudinal data from patients, health care professionals, or caregivers; treatment decision-making; or patient characteristics that predicted antipsychotic use for bipolar disorder. Results were analyzed descriptively. Results: Of the 209 references identified, 11 met the inclusion criteria and were evaluated. These articles provided attitudinal information from 1,418 patients with bipolar disorder and 1,282 treating clinicians. Patients’ attitudes toward antipsychotics were generally positive. Longer duration of clinical stability was associated with positive attitudes. Implementation of psychoeducational and adherence enhancement strategies could improve patient attitudes. Limited data suggest clinicians’ perceptions of antipsychotic efficacy and tolerability may have the greatest impact on their prescribing patterns. Because the current real-world evidence base is inadequate, clinician attitudes

Use of physical restraints and antipsychotic medications in nursing homes: a cross-national study.

Science.gov (United States)

Feng, Zhanlian; Hirdes, John P; Smith, Trevor F; Finne-Soveri, Harriet; Chi, Iris; Du Pasquier, Jean-Noel; Gilgen, Ruedi; Ikegami, Naoki; Mor, Vincent

2009-10-01

This study compares inter- and intra-country differences in the prevalence of physical restraints and antipsychotic medications in nursing homes, and examines aggregated resident conditions and organizational characteristics correlated with these treatments. Population-based, cross-sectional data were collected using a standardized Resident Assessment Instrument (RAI) from 14,504 long-term care facilities providing nursing home level services in five countries participating in the interRAI consortium, including Canada, Finland, Hong Kong (Special Administrative Region, China), Switzerland, and the United States. Facility-level prevalence rates of physical restraints and antipsychotic use were examined both between and within the study countries. The prevalence of physical restraint use varied more than five-fold across the study countries, from an average 6% in Switzerland, 9% in the US, 20% in Hong Kong, 28% in Finland, and over 31% in Canada. The prevalence of antipsychotic use ranged from 11% in Hong Kong, between 26-27% in Canada and the US, 34% in Switzerland, and nearly 38% in Finland. Within each country, substantial variations existed across facilities in both physical restraint and antipsychotic use rates. In all countries, neither facility case mix nor organizational characteristics were particularly predictive of the prevalence of either treatment. There exists large, unexplained variability in the prevalence of physical restraint and antipsychotic use in nursing home facilities both between and within countries. Since restraints and antipsychotics are associated with adverse outcomes, it is important to understand the idiosyncratic factors specific to each country that contribute to variation in use rates. Copyright (c) 2009 John Wiley & Sons, Ltd.

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.

Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research

DEFF Research Database (Denmark)

Shane, Elizabeth; Burr, David; Ebeling, Peter R

2010-01-01

Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent...... to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents...... published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete...

Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly.

Science.gov (United States)

Percudani, Mauro; Barbui, Corrado; Fortino, Ida; Tansella, Michele; Petrovich, Lorenzo

2005-10-01

Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

The Safety of Second-Generation Antipsychotics During Pregnancy

DEFF Research Database (Denmark)

Damkier, Per; Videbech, Poul

2018-01-01

The issue of antipsychotic treatment during pregnancy is subject to substantial uncertainty and some controversy among healthcare providers, specifically pertaining to second-generation antipsychotics (SGAs) that are subject to a large gap in safety data during pregnancy compared...... with antidepressants. The amount of safety data for the use of SGAs during pregnancy is rapidly increasing, thus constantly changing the level of evidence. We performed a clinically focused review on the safety of SGA during pregnancy. Twenty-three studies provided various pregnancy outcomes for 14,382 pregnant women...... exposed to an SGA during pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not associated with increased risks of major congenital malformations, whereas risperidone and paliperidone may be associated with a very minor increased risk of congenital malformations. Safety data...

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

Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients

DEFF Research Database (Denmark)

Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna

2014-01-01

.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...... 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 into the pathophysiology associated with metabolic side effects of antipsychotic...

The art and science of switching antipsychotic medications, part 2.

Science.gov (United States)

Weiden, Peter J; Miller, Alexander L; Lambert, Tim J; Buckley, Peter F

2007-01-01

In the presentation "Switching and Metabolic Syndrome," Weiden summarizes reasons to switch antipsychotics, highlighting weight gain and other metabolic adverse events as recent treatment targets. In "Texas Medication Algorithm Project (TMAP)," Miller reviews the TMAP study design, discusses results related to the algorithm versus treatment as usual, and concludes with the implications of the study. Lambert's presentation, "Dosing and Titration Strategies to Optimize Patient Outcome When Switching Antipsychotic Therapy," reviews the decision-making process when switching patients' medication, addresses dosing and titration strategies to effectively transition between medications, and examines other factors to consider when switching pharmacotherapy.

Computerized tomography in atypical Pott's disease

International Nuclear Information System (INIS)

Cabrera, M.N.B.; Wang, E.H.M.

1993-01-01

Classical Pott's disease is described as a two-vertebrae disease with the destruction of the intervening invertebral disc. Computerized tomography has been used in the differential diagnosis of spine infections and neoplasms. We reviewed CT scans of patients seen at the Philippine General Hospital over a two-year period with atypical presentations of atypical tuberculous spondylitis. We used the computerized tomography findings described as characteristic of classical Pott's disease as criteria in evaluating the CT scans of patients diagnosed to have Atypical Pott's Disease. Although the number of patients prevented sensitivity and specificity studies to be done, our results strongly suggest that the same CT criteria used to diagnose Classical Pott's Disease may also be used to diagnose Pott's disease in its atypical form. (Author.). 13 refs

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

Science.gov (United States)

Rodgers, Stephanie; Vandeleur, Caroline L; Ajdacic-Gross, Vladeta; Aleksandrowicz, Aleksandra A; Strippoli, Marie-Pierre F; Castelao, Enrique; Glaus, Jennifer; Lasserre, Aurélie M; Müller, Mario; Rössler, Wulf; Angst, Jules; Preisig, Martin

2016-01-15

Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. The use of cross-sectional data does not allow causal conclusions. This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care. Copyright © 2015 Elsevier B.V. All rights reserved.

Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

DEFF Research Database (Denmark)

Fink-Jensen, Anders; Schmidt, Lene S; Dencker, Ditte

2011-01-01

of the striatum, suggesting a role for muscarinic M4 receptors in the motor side effects of antipsychotics, and in the alleviation of these side effects by anticholinergics. Here we investigated the potential role of the muscarinic M4 receptor in catalepsy induced by antipsychotics (haloperidol and risperidone...

Consumers' questions about antipsychotic medication : revealing safety concerns and the silent voices of young men

NARCIS (Netherlands)

Weersink, Rianne A; Taxis, Katja; McGuire, Treasure M; van Driel, Mieke L

2015-01-01

PURPOSE: Little is known about consumer information needs regarding antipsychotic medicines. Medicines call centre (MCC)-derived data are underutilised; and could provide insight into issues of importance to consumers. This study aimed to explore consumers' information needs about antipsychotic

Atypical Antidepressants

Science.gov (United States)

... health-medications/index.shtml. Accessed May 16, 2016. Hirsch M, et al. Atypical antidepressants: Pharmacology, admininstration, and ... www.uptodate.com/home. Accessed May 23, 2016. Hirsch M, et al. Discontinuing antidepressant medications in adults. ...

Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study.

Science.gov (United States)

Wu, Chi-Shin; Chang, Chia-Ming; Tsai, Yu-Ting; Huang, Ya-Wen; Tsai, Hui-Ju

2015-09-01

To investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. Among patients with schizophrenia (ICD-9-CM code 295), 605 cases with hip fracture and 2,828 matched controls were identified from 2002 to 2011 using the National Health Insurance Research Database in Taiwan. The authors conducted a nested case-control study to investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. The modifiable effects of age and gender were evaluated by stratified analysis. In addition, the effects of antipsychotic use, antipsychotic classes, and receptor-binding profiles of antipsychotics, individually, on hip fracture were estimated, and potential confounding factors were adjusted in subsequent analysis. Conditional logistic regressions were applied to determine the effect of antipsychotic treatment on hip fracture. Current antipsychotic use was associated with an increased risk for hip fracture (adjusted odds ratio [AOR] = 1.61; 95% CI, 1.24-2.10). Among current users, new users had a higher risk of hip fracture (AOR = 4.28; 95% CI, 1.76-10.36) than past users (AOR = 1.11; 95% CI, 0.79-1.56). In addition, a significant increased risk of hip fracture was noted in schizophrenia subjects with first-generation antipsychotic use (AOR = 1.59; 95%CI, 1.15-2.20) but not in those with second-generation antipsychotic use (AOR = 1.16; 95% CI, 0.91-1.48). These results extend previous findings and demonstrate an increased risk of hip fracture associated with antipsychotic use in schizophrenia subjects. Further investigation is needed to dissect the underlying mechanisms related to the effect of antipsychotic use on hip fracture in subjects at risk. © Copyright 2015 Physicians Postgraduate Press, Inc.

Distribution of serine protease autotransporters of Enterobacteriaceae in typical and atypical enteroaggregative Escherichia coli.

Science.gov (United States)

Andrade, Fernanda B; Abreu, Afonso G; Nunes, Kamila O; Gomes, Tânia A T; Piazza, Roxane M F; Elias, Waldir P

2017-06-01

Enteroaggregative Escherichia coli (EAEC) is an agent of acute and persistent diarrhea worldwide, categorized in typical or atypical subgroups. Some EAEC virulence factors are members of the serine protease autotransporters of Enterobacteriaceae (SPATE). The presence of SPATE-encoding genes of different E. coli pathotypes was searched in a large collection of EAEC strains, and a possible association between SPATEs and E. coli phylogroups was investigated. Among 108 typical and 85 atypical EAEC, pic was the most prevalent gene, detected in 47.1% of the strains, followed by sat (24.3%), espI (21.2%), pet (19.2%), sepA (13.5%), sigA (4.1%), eatA (4.1%), vat (1.0%), espP and tsh, detected in one strain (0.5%) each; while epeA and espC were not detected. Phylogenetic analysis demonstrated that 39.9% of the strains belonged to group A, 23.3% to B1, 10.9% to B2, 7.8% to D, 8.8% to E and 1.5% to F. The majority of the SPATE genes were distributed in typical and atypical strains without association with any phylogroup. In addition, pic and pet were strongly associated with typical EAEC and sepA was detected in close association with atypical EAEC. Our data indicate that SPATEs may represent important virulence traits in both subgroups of EAEC. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased use of antipsychotic long-acting injections with community treatment orders.

Science.gov (United States)

Patel, Maxine X; Matonhodze, Jane; Baig, Mirza K; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S

2011-04-01

Community treatment orders (CTOs) are increasingly being used, despite a weak evidence base, and problems continue regarding Second Opinion Appointed Doctor (SOAD) certification of medication. The aim of the current study was to describe current CTO usage regarding patient characteristics, prescribed medication and CTO conditions. A 1-year prospective cohort study with consecutive sampling was conducted for all patients whose CTO was registered in a large mental health trust. Only the first CTO for each patient was included. Measures included sociodemographic variables, psychiatric diagnosis, CTO date of initiation and conditions, psychotropic medication and date of SOAD certification for medication. This study was conducted in the first year of CTO legislation in England and Wales. A total of195 patients were sampled (mean age 40.6 years, 65% male, 52% black ethnic origin). There was significant geographical variability in rates of CTO use (χ(2) = 11.3, p = 0.012). A total of 53% had their place of residence specified as a condition and 29% were required to allow access into their homes. Of those with schizophrenia, 64% were prescribed an antipsychotic long-acting injection (LAI). Of the total group, 7% received high-dose antipsychotics, 10% were prescribed two antipsychotics and only 15% received SOAD certification in time. There was geographical and ethnic variation in CTO use but higher rates of hospital detention in minority ethnic groups may be contributory. Most patients were prescribed antipsychotic LAIs and CTO conditions may not follow the least restrictive principle.

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.

Detection of respiratory bacterial pathogens causing atypical pneumonia by multiplex Lightmix® RT-PCR.

Science.gov (United States)

Wagner, Karoline; Springer, Burkard; Imkamp, Frank; Opota, Onya; Greub, Gilbert; Keller, Peter M

2018-04-01

Pneumonia is a severe infectious disease. In addition to common viruses and bacterial pathogens (e.g. Streptococcus pneumoniae), fastidious respiratory pathogens like Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp. can cause severe atypical pneumonia. They do not respond to penicillin derivatives, which may cause failure of antibiotic empirical therapy. The same applies for infections with B. pertussis and B. parapertussis, the cause of pertussis disease, that may present atypically and need to be treated with macrolides. Moreover, these fastidious bacteria are difficult to identify by culture or serology, and therefore often remain undetected. Thus, rapid and accurate identification of bacterial pathogens causing atypical pneumonia is crucial. We performed a retrospective method evaluation study to evaluate the diagnostic performance of the new, commercially available Lightmix ® multiplex RT-PCR assay that detects these fastidious bacterial pathogens causing atypical pneumonia. In this retrospective study, 368 clinical respiratory specimens, obtained from patients suffering from atypical pneumonia that have been tested negative for the presence of common agents of pneumonia by culture and viral PCR, were investigated. These clinical specimens have been previously characterized by singleplex RT-PCR assays in our diagnostic laboratory and were used to evaluate the diagnostic performance of the respiratory multiplex Lightmix ® RT-PCR. The multiplex RT-PCR displayed a limit of detection between 5 and 10 DNA copies for different in-panel organisms and showed identical performance characteristics with respect to specificity and sensitivity as in-house singleplex RT-PCRs for pathogen detection. The Lightmix ® multiplex RT-PCR assay represents a low-cost, time-saving and accurate diagnostic tool with high throughput potential. The time-to-result using an automated DNA extraction device for respiratory specimens followed by multiplex RT-PCR detection was

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.

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...

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.

Antipsychotic treatment dosing profile in patients with schizophrenia evaluated with electronic monitoring (MEMS®).

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Acosta, Francisco J; Ramallo-Fariña, Yolanda; Bosch, Esperanza; Mayans, Teresa; Rodríguez, Carlos J; Caravaca, Ana

2013-05-01

Although the Medication Event Monitoring System (MEMS®) device offers accurate information on treatment dosing profile, such profile has never been studied in patients with schizophrenia. Enhancing our knowledge on this issue would help in developing intervention strategies to improve adherence to antipsychotic treatment in these patients. 74 outpatients with schizophrenia were monitored with the MEMS device for a 3-month period, for evaluation of antipsychotic treatment dosing profile, possible influence of medication schedule-related variables, adherence to treatment--considering dose intake within prescribed timeframes--and possible Hawthorne's effect of using the MEMS device. Dose-omission gaps occurred in 18.7% of monitoring days, most frequently during weekends, almost significantly. Almost one-third of prescribed doses were taken out of prescribed time. Neither the prescribed number of daily doses nor the indicated time of the day for dose intake (breakfast, dinner), were associated with correct antipsychotic dosing. Excess-dose was rare in general, and more frequent out of prescribed dose timeframe. No Hawthorne's effect was found for the MEMS device. Adherence reached only 35% according to a definition that included dose intake within prescribed timeframes. Antipsychotic treatment dosing was considerably irregular among patients with schizophrenia. Strategies to reduce dose-omission gaps and increase dosing within prescribed timeframes seem to be necessary. Gaining knowledge on precise oral antipsychotic dosing profiles or the influence of schedule-related variables may be useful to design strategies towards enhancing adherence. There appears to be no Hawthorne's effect associated with the use of MEMS devices in outpatients with schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription

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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.

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.

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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.

Association Study of 60 Candidate Genes with Antipsychotic-induced Weight Gain in Schizophrenia Patients.

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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.

Atypical disease phenotypes in pediatric ulcerative colitis

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Levine, Arie; de Bie, Charlotte I; Turner, Dan

2013-01-01

Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome.

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Quezada, Julio; Coffman, Keith A

2018-01-01

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

Understanding the Uncanny: Both Atypical Features and Category Ambiguity Provoke Aversion toward Humanlike Robots

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Megan K. Strait

2017-08-01

Full Text Available Robots intended for social contexts are often designed with explicit humanlike attributes in order to facilitate their reception by (and communication with people. However, observation of an “uncanny valley”—a phenomenon in which highly humanlike entities provoke aversion in human observers—has lead some to caution against this practice. Both of these contrasting perspectives on the anthropomorphic design of social robots find some support in empirical investigations to date. Yet, owing to outstanding empirical limitations and theoretical disputes, the uncanny valley and its implications for human-robot interaction remains poorly understood. We thus explored the relationship between human similarity and people's aversion toward humanlike robots via manipulation of the agents' appearances. To that end, we employed a picture-viewing task (Nagents = 60 to conduct an experimental test (Nparticipants = 72 of the uncanny valley's existence and the visual features that cause certain humanlike robots to be unnerving. Across the levels of human similarity, we further manipulated agent appearance on two dimensions, typicality (prototypic, atypical, and ambiguous and agent identity (robot, person, and measured participants' aversion using both subjective and behavioral indices. Our findings were as follows: (1 Further substantiating its existence, the data show a clear and consistent uncanny valley in the current design space of humanoid robots. (2 Both category ambiguity, and more so, atypicalities provoke aversive responding, thus shedding light on the visual factors that drive people's discomfort. (3 Use of the Negative Attitudes toward Robots Scale did not reveal any significant relationships between people's pre-existing attitudes toward humanlike robots and their aversive responding—suggesting positive exposure and/or additional experience with robots is unlikely to affect the occurrence of an uncanny valley effect in humanoid robotics

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

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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.

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention

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Hayes, Spencer J.; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J.

2016-01-01

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only…

A naturally occurring cowpox virus with an ectromelia virus A-type inclusion protein gene displays atypical A-type inclusions.

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Okeke, Malachy Ifeanyi; Hansen, Hilde; Traavik, Terje

2012-01-01

Human orthopoxvirus (OPV) infections in Europe are usually caused by cowpox virus (CPXV). The genetic heterogeneity of CPXVs may in part be due to recombination with other OPV species. We describe the characterization of an atypical CPXV (CPXV-No-H2) isolated from a human patient in Norway. CPXV-No-H2 was characterized on the basis of A-type inclusion (ATI) phenotype as well as the DNA region containing the p4c and atip open reading frames. CPXV-No-H2 produced atypical V(+/) ATI, in which virions are on the surface of ATI but not within the ATI matrix. Phylogenetic analysis showed that the atip gene of CPXV-No-H2 clustered closely with that of ectromelia virus (ECTV) with a bootstrap support of 100% whereas its p4c gene is diverged compared to homologues in other OPV species. By recombination analysis we identified a putative crossover event at nucleotide 147, downstream the start of the atip gene. Our results suggest that CPXV-No-H2 originated from a recombination between CPXV and ECTV. Our findings are relevant to the evolution of OPVs. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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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.

Vitamin E for antipsychotic-induced tardive dyskinesia.

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Soares-Weiser, Karla; Maayan, Nicola; Bergman, Hanna

2018-01-17

Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Vitamin E has been proposed as a treatment to prevent or decrease TD. The primary objective was to determine the clinical effects of vitamin E in people with schizophrenia or other chronic mental illness who had developed antipsychotic-induced TD.The secondary objectives were:1. to examine whether the effect of vitamin E was maintained as duration of follow-up increased;2. to test the hypothesis that the use of vitamin E is most effective for those with early onset TD (less than five years) SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. We included reports if they were controlled trials dealing with people with antipsychotic-induced TD and schizophrenia who remained on their antipsychotic medication and had been randomly allocated to either vitamin E or to a placebo, no intervention, or any other intervention. We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE. The review now includes 13 poorly reported randomised trials (total 478 people), all participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear difference between vitamin E and placebo for the outcome of TD: not improved to a clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low-quality evidence

Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis.

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de Silva, Varuni Asanka; Suraweera, Chathurie; Ratnatunga, Suhashini S; Dayabandara, Madhubashinee; Wanniarachchi, Nimali; Hanwella, Raveen

2016-10-03

Most antipsychotics are associated with weight gain and other metabolic complications. Several randomized trials have shown metformin to be effective, but this still hasn't been included in clinical guidelines on managing antipsychotic induced weight gain. All double blind placebo controlled trials assessing the efficacy of metformin in the treatment of antipsychotic induced weight gain were included. Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE were searched for the period January 2000-December 2015. Meta-analysis was carried out using the random effects model. Meta analysis of 12 published studies with a total of 743 patients found that in patients treated with antipsychotics, metformin treatment resulted in significantly better anthropometric and metabolic parameters than placebo. The mean change in weight was -3.27 kg (95 % CI -4.66 to -1.89) (Z = 4.64, p resistance index [-1.49 (95 % CI -2.40 to -0.59)] but not fasting blood sugar [-2.48 mg/dl (95 % CI -5.54 to 0.57]. This meta-analysis confirms that metformin is effective in treating antipsychotic induced weight gain in patients with schizophrenia or schizoaffective disorder.

Atypical Cutaneous Manifestations in Syphilis.

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Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

2016-05-01

Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

OpenAIRE

Ebdrup Bjørn H; Knop Filip K; Ishøy Pelle L; Rostrup Egill; Fagerlund Birgitte; Lublin Henrik; Glenthøj Birte

2012-01-01

Abstract Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the g...

Gender differences in attitudes towards antipsychotic medications in patients with schizophrenia.

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Zhou, Jiansong; Xiang, Yu-Tao; Li, Qiguang; Zhu, Xiaomin; Li, Wen; Ungvari, Gabor S; Ng, Chee H; Ongur, Dost; Wang, Xiaoping

2016-11-30

Non-adherence was more frequent in male than in female psychiatric patients. This multi-center study in China examined the gender difference with regard to attitude towards antipsychotic medications and its associations with socio-demographic variables, insight, and psychopathology. Patients' basic socio-demographic and clinical data were collected. Psychopathology and insight were measured with the Symptom Checklist-90 (SCL-90) and the Insight and Treatment Attitudes Questionnaire (ITAQ), respectively. Their attitudes towards antipsychotic medications were assessed by two standardized questions. Nearly 39.6% (109/275) males and 31.1% (70/225) females reported negative attitudes towards antipsychotic medications. Binary logistic regression revealed that in males single marital status (OR=2.9, 95% CI=1.3-6.4), rural residence (OR=0.4, 95% CI=0.2-0.7), longer duration of schizophrenia (OR=1.0, 95% CI=1.0-1.1), knowledge of medication (OR=1.5, 95% CI=1.3-1.6) and the SCL-90 hostility subscale (OR=0.9, 95% CI=0.9-1.0) were contributors to negative attitudes. In female patients, knowledge about medications (OR=1.4, 95% CI=1.3-1.6), the SCL-90 somatization (OR=0.8, 95% CI=0.8-0.9) and anxiety (OR=1.1, 95% CI=1.0-1.2) subscales were contributors to negative attitudes. The study suggested that different psychosocial and clinical factors accounted for the negative attitude towards antipsychotic treatment in male and female patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Case of Probable Amisulpride Induced Mania after Eight Months of Therapy

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Prakash Thapa

2017-01-01

Full Text Available Development of manic symptoms during treatment with atypical antipsychotics can be a troublesome side effect that has been described with most atypical antipsychotics. However, reports of amisulpride induced mania have been rare. Here, we report the case of an 18-year-old male patient diagnosed with schizophrenia, who developed manic symptoms while on treatment with amisulpride. While previous reports have described occurrence of mania within days to three months of treatment with amisulpride, we report a case where manic symptoms occurred after around eight months of therapy. We have also attempted to describe the possible risk factors based on the available case studies.

Antipsychotic Use and Hospitalization Among Older Assisted Living Residents: Does Risk Vary by Frailty Status?

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Stock, Kathryn J; Hogan, David B; Lapane, Kate; Amuah, Joseph E; Tyas, Suzanne L; Bronskill, Susan E; Morris, Andrew M; Bell, Chaim M; Jeffs, Lianne; Maxwell, Colleen J

2017-07-01

To examine associations between baseline frailty measures, antipsychotic use, and hospitalization over 1 year and whether hospitalization risk associated with antipsychotic use varies by frailty level. In this prospective cohort study of 1,066 residents (mean age: 85 years; 77% women) from the Alberta Continuing Care Epidemiological Studies, trained research nurses conducted comprehensive resident assessments at baseline (2006-2007) for sociodemographic characteristics, health conditions, frailty status, behavioral problems, and all medications consumed during the past 3 days. Two separate measures of frailty were assessed, the Cardiovascular Health Study (CHS) phenotype and an 86-item Frailty Index (FI). Time to first hospitalization during follow-up was determined via linkage with the Alberta Inpatient Discharge Abstract Database. Baseline frailty status (both measures), but not antipsychotic use, was significantly associated with hospitalization over 1 year. When stratified by frailty, FI-defined frail residents using antipsychotics showed a significantly increased risk for hospitalization (adjusted HR: 1.54; 95% CI: 1.01-2.36) compared with frail nonusers. CHS-defined frail antipsychotic users versus frail nonusers also showed an elevated risk (adjusted HR: 1.67; 95% CI: 0.96-2.88). Nonfrail residents using antipsychotics were significantly less likely to be hospitalized compared with nonfrail nonusers whether defined by the FI (adjusted HR: 0.62; 95% CI: 0.39-0.99) or CHS criteria (adjusted HR: 0.62; 95% CI: 0.40-0.96). Frailty measures may be helpful in identifying those who are particularly vulnerable to adverse effects and those who may experience benefit with treatment. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

[Maintenance Treatment With Antipsychotics for Adult Patients Diagnosed With Schizophrenia].

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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.

Imaging as tool to investigate psychoses and antipsychotics

NARCIS (Netherlands)

Booij, Jan; van Amelsvoort, Thérèse

2012-01-01

The results of imaging studies have played an important role in the formulation of hypotheses regarding the etiology of psychosis and schizophrenia, as well as in our understanding of the mechanisms of action of antipsychotics. Since this volume is primarily directed to molecular aspects of

Renal Failure in Dementia with Lewy Bodies Presenting as Catatonia

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Robert Fekete

2013-01-01

Full Text Available Catatonia, originally described by Karl Kahlbaum in 1874, may be regarded as a set of clinical features found in a subtype of schizophrenia, but the syndrome may also stem from organic causes including vascular parkinsonism, brain masses, globus pallidus lesions, metabolic derangements, and pharmacologic agents, especially first generation antipsychotics. Catatonia may include paratonia, waxy flexibility (cerea flexibilitas, stupor, mutism, echolalia, and catalepsy (abnormal posturing. A case of catatonia as a result of acute renal failure in a patient with dementia with Lewy bodies is described. This patient recovered after intravenous fluid administration and reinstitution of the atypical dopamine receptor blocking agent quetiapine, but benzodiazepines and amantadine are additional possible treatments. Recognition of organic causes of catatonia leads to timely treatment and resolution of the syndrome.

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

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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

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...

Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

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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

Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments.

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Das, Chandan; Mendez, Guillermo; Jagasia, Sonal; Labbate, Lawrence A

2012-08-01

Weight gain in schizophrenia, particularly secondary to second-generation antipsychotic (SGA) use, is a common adverse effect and often is associated with significant physical and psychological morbidity. We performed a critical literature review of all controlled clinical trials for pharmacologic and/or behavioral management of SGA-induced weight gain in schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis was performed to estimate and compare weight changes for various medications and behavioral interventions. Sample sizes generally were small. Clinical trials were 6 weeks to 1 year, and weight loss was modest with any treatment. Although several adjunctive pharmacologic treatments showed no weight loss, sibutramine, metformin, and topiramate showed some benefit. Amantadine and orlistat were somewhat less effective and had lower rates of tolerability. Among the behavioral therapies, nutritional counseling combined with exercise showed the most benefit. Behavioral therapies, although modest, showed the most consistent benefits compared with controls. Scheduled pharmacologic treatment to prevent weight gain or promote weight loss in schizophrenia patients on SGA therapy is limited based on current studies. Switching antipsychotic agents has not been established as a long-term solution. Additional long-term studies are required to influence clinical practice.

Oral health impacts of medications used to treat mental illness.

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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.

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

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.

Stability and development of psychotic symptoms and the use of antipsychotic medication - long-term follow-up

DEFF Research Database (Denmark)

Gotfredsen, D R; Wils, R S; Hjorthøj, C

2017-01-01

BACKGROUND: Few studies have evaluated the development in the use of antipsychotic medication and psychotic symptoms in patients with first-episode psychosis on a long-term basis. Our objective was to investigate how psychotic symptoms and the use of antipsychotic medication changed over a 10-yea...

Is antipsychotic polypharmacy associated with metabolic syndrome even after adjustment for lifestyle effects?: a cross-sectional study

Directory of Open Access Journals (Sweden)

Okumura Yasuyuki

2011-07-01

Full Text Available Abstract Background Although the validity and safety of antipsychotic polypharmacy remains unclear, it is commonplace in the treatment of schizophrenia. This study aimed to investigate the degree that antipsychotic polypharmacy contributed to metabolic syndrome in outpatients with schizophrenia, after adjustment for the effects of lifestyle. Methods A cross-sectional survey was carried out between April 2007 and October 2007 at Yamanashi Prefectural KITA hospital in Japan. 334 patients consented to this cross-sectional study. We measured the components consisting metabolic syndrome, and interviewed the participants about their lifestyle. We classified metabolic syndrome into four groups according to the severity of metabolic disturbance: the metabolic syndrome; the pre-metabolic syndrome; the visceral fat obesity; and the normal group. We used multinomial logistic regression models to assess the association of metabolic syndrome with antipsychotic polypharmacy, adjusting for lifestyle. Results Seventy-four (22.2% patients were in the metabolic syndrome group, 61 (18.3% patients were in the pre-metabolic syndrome group, and 41 (12.3% patients were in visceral fat obesity group. Antipsychotic polypharmacy was present in 167 (50.0% patients. In multinomial logistic regression analyses, antipsychotic polypharmacy was significantly associated with the pre-metabolic syndrome group (adjusted odds ratio [AOR], 2.348; 95% confidence interval [CI], 1.181-4.668, but not with the metabolic syndrome group (AOR, 1.269; 95%CI, 0.679-2.371. Conclusions These results suggest that antipsychotic polypharmacy, compared with monotherapy, may be independently associated with an increased risk of having pre-metabolic syndrome, even after adjusting for patients' lifestyle characteristics. As metabolic syndrome is associated with an increased risk of cardiovascular mortality, further studies are needed to clarify the validity and safety of antipsychotic polypharmacy.

[French Society for Biological Psychiatry and Neuropsychopharmacology task force: Formal Consensus for the prescription of depot antipsychotics].

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Samalin, L; Abbar, M; Courtet, P; Guillaume, S; Lancrenon, S; Llorca, P-M

2013-12-01

Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

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Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

2010-01-01

This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

Adjunctive antipsychotic in the treatment of body dysmorphic disorder - A retrospective naturalistic case note study.

Science.gov (United States)

Rashid, Haroon; Khan, Akif A; Fineberg, Naomi A

2015-06-01

A retrospective naturalistic case note study to determine the frequency, co-morbidity and treatment-response of body dysmorphic disorder (BDD). Records from 280 patients attending a highly specialised obsessive-compulsive disorder (OCD)/BDD service were analysed. The clinical outcome was measured either through scoring of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) for OCD/BDD, or textual analysis of case notes for evidence of symptomatic improvement, treatment tolerability, and premature disengagement. A total of 32 patients (11.43%) were diagnosed with BDD. Of these, 28 (87.5%) had at least one co-morbidity. All patients were offered cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitor (SSRI). Adjunctive low-dose antipsychotic was prescribed for 21 (66%) patients. Overall, 18/32 (56%) responded, and 7/32 (22%) disengaged prematurely. Patients offered antipsychotic, SSRI and CBT (n = 21) were compared with those offered SSRI and CBT only (n = 11). The treatment was well-tolerated. Whereas there was no significant inter-group difference in the clinical response rate, premature disengagement occurred less frequently in the antipsychotic-treated patients (9.5% versus 45%; Fisher's Exact Test P = 0.0318). BDD frequently presents with co-morbidity, treatment-resistance and premature disengagement. Adjunctive antipsychotic was associated with significantly better treatment adherence, but responder rates did not differ significantly, possibly related to the small sample-size. A well-powered randomised controlled study is warranted, to determine clinical outcomes with adjunctive antipsychotic in BDD.

Atypically presenting kaposiform hemangioendothelioma of the knee: ultrasound findings.

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Erdem Toslak, Iclal; Stegman, Matthew; Reiter, Michael P; Barkan, Güliz A; Borys, Dariusz; Lim-Dunham, Jennifer E

2018-04-10

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of early childhood and infancy. Kasabach-Merritt phenomenon, a common complication of KHE, is characterized by life-threatening thrombocytopenia, hemolytic anemia, and consumption coagulopathy. There may be atypical cases that do not present with Kasabach-Merritt phenomenon and do have atypical imaging findings. Knowledge of atypical imaging features may assist radiologists in identifying KHE. In this report, we present a 4-year-old case of KHE with atypical ultrasound findings.

Prevalence and Correlates of “High Dose” Antipsychotic Prescribing ...

African Journals Online (AJOL)

USA) version 16 and summarized into means and standard deviations. ... employed (P = 0.794), living in an urban area (P = 0.37), religion (P .... As in the study in Hong Kong,[20] a prior history ... antipsychotic prescriptions in Hong Kong.

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