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Sample records for atypical antipsychotic drugs

  1. The influence of atypical antipsychotic drugs on sexual function

    Directory of Open Access Journals (Sweden)

    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

  2. The influence of atypical antipsychotic drugs on sexual function.

    Science.gov (United States)

    Just, Marek J

    2015-01-01

    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.

  3. Atypical antipsychotic drugs selectively increase neurotensin efflux in dopamine terminal regions

    OpenAIRE

    Radke, James M.; Owens, Michael J.; Ritchie, James C.; Nemeroff, Charles B.

    1998-01-01

    Typical antipsychotic drugs, such as haloperidol and chlorpromazine, increase synthesis of the neuropeptide neurotensin (NT) in both the striatum and the nucleus accumbens, whereas atypical antipsychotic drugs, such as clozapine and olanzapine, do so only in the nucleus accumbens. By using in vivo microdialysis, we now report that acute administration of haloperidol, clozapine, or olanzapine failed to alter the release of NT in either the striatum or nucleus accumbens. In contrast, chronic ad...

  4. Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

    OpenAIRE

    Sumiyoshi, Tomiki; Higuchi, Yuko; Uehara, Takashi

    2013-01-01

    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 (AAPDs), e.g., clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone...

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

    Science.gov (United States)

    Sarkar, Siddharth; Gupta, Nitin

    2017-08-01

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

  6. Post-drug consequences of chronic atypical antipsychotic drug administration on the ability to adjust behavior based on feedback in young monkeys

    NARCIS (Netherlands)

    Mandell, D.J.; Unis, A.; Sackett, G.P.

    2011-01-01

    Rationale: Atypical antipsychotic drugs are characterized by their affinity for serotonin and dopamine receptors. The dopaminergic system undergoes developmental changes during childhood, making it vulnerable to external influences such as drug administration. Objective: The purpose of this study

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. ATYPICAL ANTIPSYCHOTICS USE IN CHILDREN AND ADOLESCENTS

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    Nataša Potočnik-Dajčman

    2002-06-01

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

  10. Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

    Science.gov (United States)

    Sumiyoshi, Tomiki; Higuchi, Yuko; Uehara, Takashi

    2013-01-01

    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 (AAPDs), 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 gamma-aminobutyric acid neurons. A novel strategy for cognitive enhancement in psychosis may be benefited 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 AAPDs 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. PMID:24137114

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

    Science.gov (United States)

    Sumiyoshi, Tomiki; Higuchi, Yuko; Uehara, Takashi

    2013-10-16

    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 (AAPDs), 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 gamma-aminobutyric acid neurons. A novel strategy for cognitive enhancement in psychosis may be benefited 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 AAPDs 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.

  12. Comparing the side effect profile of the Atypical Antipsychotics | Alao ...

    African Journals Online (AJOL)

    Post clozapine, the Food and Drug Administration (FDA) has approved the use of four newer atypical antipsychotics; risperidone, olanzapine, quetiapine and ziprasidone for the treatment of schizophrenia. Because of their dual serotonin and dopamine receptor blocking abilities, atypical antipsychotics have greater efficacy ...

  13. Relationship between Dose, Drug Levels, and D2 Receptor Occupancy for the Atypical Antipsychotics Risperidone and Paliperidone

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    Votaw, J. R.; Ritchie, J.; Howell, L. L.

    2012-01-01

    Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses of risperidone and paliperidone (the 9-OH metabolite of risperidone) and compared with multiple off-drug scans in each animal. The half-life of the two drugs in these monkeys was determined to be between 3 and 4 h, and drug was administered by a constant infusion through an intragastric catheter. The D2R occupancy of antipsychotic was determined in the caudate, putamen, ventral striatum, and four prefrontal and temporal cortical regions and was related to serum and cerebrospinal fluid drug levels. Repeated 2-week treatment with risperidone or paliperidone did not produce lasting changes in D2R binding potential in any region examined. As expected, D2R binding potential was highest in the caudate and putamen and was approximately one-third that level in the ventral striatum and 2% of that level in the cortical regions. We found dose-dependent D2R occupancy for both risperidone and paliperidone in both basal ganglia and cortical regions of interest. We could not find evidence of regional variation in D2R occupancy of either drug. Comparison of D2R occupancy and serum drug levels supports a target of 40 to 80 ng/ml active drug for these two atypical antipsychotics. PMID:22214649

  14. Discriminative stimulus properties of the atypical antipsychotic amisulpride: comparison to its isomers and to other benzamide derivatives, antipsychotic, antidepressant, and antianxiety drugs in C57BL/6 mice.

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    Donahue, Timothy J; Hillhouse, Todd M; Webster, Kevin A; Young, Richard; De Oliveira, Eliseu O; Porter, Joseph H

    2017-12-01

    Racemic (RS)-amisulpride (Solian®) is an atypical antipsychotic drug used to treat schizophrenia and dysthymia. Blockade of dopamine D2/D3 and/or serotonin 5-HT7 receptors is implicated in its pharmacological effects. While the (S)-amisulpride isomer possesses a robust discriminative cue, discriminative stimulus properties of (RS)-amisulpride have not been evaluated. The present study established (RS)-amisulpride as a discriminative stimulus and assessed amisulpride-like effects of amisulpride stereoisomers, other benzamide derivatives, and antipsychotic, antidepressant, and anxiolytic drugs. Adult, male C57BL/6 mice were trained to discriminate 10 mg/kg (RS)-amisulpride from vehicle in a two-lever food-reinforced operant conditioning task. (RS)-Amisulpride's discriminative stimulus was dose-related, time-dependent, and stereoselective. (S)-Amisulpride (an effective dose of 50% (ED50) = 0.21 mg/kg) was three times more potent than (RS)-amisulpride (ED50 = 0.60 mg/kg) or (R)-amisulpride (ED50 = 0.68 mg/kg). (RS)-Amisulpride generalized fully to the structurally related atypical antipsychotic/antidysthymia drug sulpiride (Sulpor®; ED50 = 7.29 mg/kg) and its (S)-enantiomer (ED50 = 9.12 mg/kg); moderate to high partial generalization [60-75% drug lever responding (%DLR)] occurred to the benzamide analogs tiapride (Tiapridal®) and raclopride, but less than 60% DLR to metoclopramide (Reglan®), nemonapride (Emilace®), and zacopride. Antipsychotic, antidepressant, and antianxiety drugs from other chemical classes (chlorpromazine, quetiapine, risperidone, and mianserin) produced 35-55% amisulpride lever responding. Lastly, less than 35% DLR occurred for clozapine, olanzapine, aripiprazole imipramine, chlordiazepoxide, and bupropion. (RS)-Amisulpride generalized to some, but not all benzamide derivatives, and it failed to generalize to any other antipsychotic, antidepressant, or antianxiety drugs tested. Interestingly, the (R)-isomer shared very strong

  15. 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.

  16. Constrictive Pericarditis Associated with Atypical Antipsychotics

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    Kuan-chin Jean Chen

    2012-01-01

    Full Text Available We report the successful surgical intervention in a case of constrictive pericarditis after long-term use of atypical antipsychotics. Pericarditis developed in our patient with a longstanding history of schizophrenia treated with atypical antipsychotics. Pericardiectomy was undertaken, and the patient's presenting symptom of shortness of breath resolved subsequently with an uneventful postoperative course.

  17. Weight change in Parkinson and Alzheimer patients taking atypical antipsychotic drugs.

    Science.gov (United States)

    Sitburana, Oraporn; Rountree, Susan; Ondo, William G

    2008-09-15

    Atypical antipsychotics (AA) are generally associated with weight gain. We determined body mass index (BMI) change in Parkinson's disease (PD) before and after taking AA and compared against PD controls and Alzheimer's disease (AD) patients on AA. In 66 consecutive PD subjects started on AA who had accurate weights for more than 6 months before and after initiation of AA, we compared weight change before and after AA use, against a control group of sixty-one sex-matched PD subjects, and against twenty-eight AD subjects taking AA. A linear regression model was created to compare weight changes. Fifty-nine PD subjects had complete data, quetiapine (n=53) and clozapine (n=6). The mean BMI change in the period before starting AA was 0.00 kg/m(2)/month over 1.95+/-1.41 years. After starting AA, subjects lost 0.03 kg/m(2)/month (95% CI 0.62-1.21, Pweight loss seen in the PD/AA group, compared to AD, suggest uniquely altered weight homeostasis in PD.

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

    Science.gov (United States)

    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.

  19. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

    DEFF Research Database (Denmark)

    Glenthoj, Andreas; Glenthøj, Birte Yding; Mackeprang, Torben

    2007-01-01

    and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks...... medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry...

  20. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

    DEFF Research Database (Denmark)

    Glenthoj, Andreas; Glenthoj, Birte Y; Mackeprang, Torben

    2007-01-01

    and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks...... or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two...

  1. Cost-effectiveness of an atypical conventional antipsychotic in South ...

    African Journals Online (AJOL)

    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.

  2. 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.

  3. Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic.

    Science.gov (United States)

    Einarson, Thomas R; Zilbershtein, Roman; Skoupá, Jana; Veselá, Sárka; Garg, Madhur; Hemels, Michiel E H

    2013-09-01

    The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots. An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables. Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates. PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.

  4. Weight change after an atypical antipsychotic switch.

    Science.gov (United States)

    Ried, L Douglas; Renner, Bernard T; Bengtson, Michael A; Wilcox, Brian M; Acholonu, Wilfred W

    2003-10-01

    Atypical antipsychotics successfully treat schizophrenia and other conditions, with a lower incidence of extrapyramidal side effects than other agents used in treatment of these disorders. However, some atypical antipsychotics are associated with weight gain. To quantify the impact on weight and identify atypical antipsychotics causing the least amount of weight gain among patients switched from risperidone to olanzapine and olanzapine to risperidone. Patients included in the study (n = 86) were > or =18 years and had received > or =2 prescriptions for risperidone or olanzapine for > or =60 days, switched to the other atypical antipsychotic, and were dispensed > or =2 prescriptions for at least 60 days after the index date. Age, weight, and body mass index (BMI) were retrospectively abstracted from automated databases containing patient-specific prescription and vital sign information. At the time of their switch, the average patient age was 53.2 years (range 25-83). The average weight change in patients switched to olanzapine (n = 47) was +2.3 kg (p = 0.01) and the BMI change was +0.8 kg/m(2) (p = 0.02). The average percent body weight change was +2.8% and the BMI change was +3.0%. The average weight change after patients switched to risperidone (n = 39) was -0.45 kg (p = 0.69) and BMI change was -0.2 kg/m2 (p = 0.64). The average percentage weight change was -0.4% and BMI change was -0.5%. Practitioners' concern regarding weight changes after switching atypical antipsychotics seems warranted and patients should be provided consistent, ongoing weight monitoring. Further investigations should examine whether weight changes associated with atypical antipsychotic treatment further jeopardize this already at-risk population for severe comorbid conditions such as hypertension, coronary artery disease, and type 2 diabetes.

  5. Atypical Antipsychotics and Inverse Agonism at 5-HT2 Receptors

    Science.gov (United States)

    Sullivan, Laura C.; Clarke, William P.; Berg, Kelly A.

    2017-01-01

    It is now well accepted that receptors can regulate cellular signaling pathways in the absence of a stimulating ligand, and inverse agonists can reduce this ligand-independent or “constitutive” receptor activity. Both the serotonin 5-HT2A and 5-HT2C receptors have demonstrated constitutive receptor activity in vitro and in vivo. Each has been identified as a target for the treatment of schizophrenia. Further, most, if not all, atypical antipsychotic drugs have inverse agonist properties at both 5-HT2A and 5-HT2C receptors. This paper describes our current knowledge of inverse agonism of atypical antipsychotics at 5-HT2A/2C receptor subtypes in vitro and in vivo. Exploiting inverse agonist properties of antipsychotic drugs may provide new avenues for drug development. PMID:26044975

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

    Science.gov (United States)

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

    1989-10-01

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

  7. Olanzapine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; 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. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to 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 reference 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 trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, 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 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole

  8. Use of atypical antipsychotics in the elderly: a clinical review

    Directory of Open Access Journals (Sweden)

    Gareri P

    2014-08-01

    Full Text Available Pietro Gareri,1 Cristina Segura-García,2 Valeria Graziella Laura Manfredi,1 Antonella Bruni,2 Paola Ciambrone,2 Gregorio Cerminara,2 Giovambattista De Sarro,2 Pasquale De Fazio2 1Elderly Health Care, Azienda Sanitaria Provinciale Catanzaro, Catanzaro, Italy; 2Department of Health Sciences, University “Magna Græcia” of Catanzaro, Catanzaro, Italy Abstract: The use of atypical antipsychotic drugs in the elderly has become wider and wider in recent years; in fact, these agents have novel receptor binding profiles, good efficacy with regard to negative symptoms, and reduced extrapyramidal symptoms. However, in recent years, the use of both conventional and atypical antipsychotics has been widely debated for concerns about their safety in elderly patients affected with dementia and the possible risks for stroke and sudden death. A MEDLINE search was made using the words elderly, atypical antipsychotics, use, schizophrenia, psychosis, mood disorders, dementia, behavioral disorders, and adverse events. Some personal studies were also considered. This paper reports the receptor binding profiles and the main mechanism of action of these drugs, together with their main use in psychiatry and the possible adverse events in elderly people. Keywords: atypical antipsychotics, dementia, elderly, psychosis, mood disorders, side effects

  9. Metformin for the Prevention of Weight Gain due to Atypical Antipsychotics

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    Nazmiye Kaya

    2011-06-01

    Full Text Available Excessive weight gain, hyperglycemia, type 2 diabetes and hyperlipidemia are significant clinical adverse effects that appear as a result of the treatment with second generation atypical antipsychotic drugs. These drugs possibly cause weight gain by stimulating appetite and increasing insulin resistance. Amantadine, nizatidine, ranitidine, famotidine, topiramate, reboxetine and metformin are notified as the effective drugs which were used in order to prevent the weight gain due to atypical antipsychotic drugs. As an antidiabetic agent, metformin draws attention due to reducing weight gain and correcting insulin resistance. The aim of this paper was to evaluate studies searching fort he effect of metformin on weight-gain due to atypical antipsychotics.

  10. Clinical utilization of atypical antipsychotics in pregnancy and lactation.

    Science.gov (United States)

    Gentile, Salvatore

    2004-01-01

    To analyze the available literature regarding the safety of atypical antipsychotics in pregnancy and lactation in order to recommend evidence-based strategies for pharmacologic management of psychosis in these conditions. We summarized the results from articles identified via MEDLINE/PubMed/TOXNET (1993-January 31, 2004), using the key terms pregnancy, lactation, breast-feeding, human milk, psychotropic drugs, atypical antipsychotics, olanzapine, quetiapine, risperidone, clozapine, ziprasidone, and aripiprazole. Retrospective studies, clinical observations, and case reports regarding the 6 atypical antipsychotics mentioned above were selected and analyzed. Extensive manual review of pertinent journals and textbooks was also performed. Reviewed studies show that olanzapine and clozapine apparently do not increase the teratogenic risk if administered to pregnant women, while evidence on quetiapine, risperidone, aripiprazole, and ziprasidone is still limited. In contrast, available information is not able to exclude unwanted serious effects associated with the use of all atypical antipsychotics on mother-infant dyads. Furthermore, more than a few studies suggest increased hyperglycemic risk for pregnant women related to atypical antipsychotic therapy during gestation. Finally, published evidence about the effects on long-term infant neurodevelopment of drug exposure through both placenta and breast milk is represented only by sporadic case reports. It is well known that potential consequences of an untreated psychotic episode may be severe and may lead to the mother attempting suicide and/or infanticide. For these reasons, clinicians need to help mothers weigh both fetal and neonatal risks of exposure to drugs against the potential risk they and their infant may incur if the psychiatric illness is not treated. On the other hand, atypical antipsychotics in pregnancy and breast-feeding do not show evident advantages in safety when compared with typical neuroleptic

  11. Use of atypical antipsychotics in the treatment of autistic disorder.

    Science.gov (United States)

    Stachnik, Joan M; Nunn-Thompson, Cheryl

    2007-04-01

    To review clinical trials and reports describing the efficacy and safety of atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) in the treatment of autistic or other pervasive developmental disorders. English-language publications from the MEDLINE database (1966-February 2007) including clinical trials, case reports, and retrospective series were reviewed. Relevant data were extracted from studies of selected atypical antipsychotics in the treatment of autistic disorder in children, adolescents, and adults. Most literature found was in the form of case reports or case series; however, several open-label and double-blind trials were also identified. Autistic disorder is a chronic neurodevelopmental disorder with limited treatment options. Nonpharmacologic approaches may be the most beneficial, but pharmacologic agents are needed for some patients with significant behavioral manifestations of the disorder. The atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) have shown some efficacy in improving certain behavioral symptoms of autistic disorder--primarily aggressiveness, hyperactivity, and self-injurious behavior. Efficacy was based on observation or changes from baseline in behavioral rating scores. Data appear to be strongest for olanzapine compared with quetiapine, with several open-label trials suggesting its efficacy. Weight gain and sedation were frequently reported adverse events with both agents. Aripiprazole has demonstrated efficacy in limited case series, with minimal adverse effects reported. Atypical antipsychotics represent a treatment option for symptoms associated with autistic disorder. However, these drugs do not affect the core symptoms of autistic disorder and are associated with potentially significant adverse effects. In addition, there is a lack of randomized controlled trials to determine the true efficacy and long-term safety of these agents in the pediatric population.

  12. 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

  13. 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.

  14. Generic penetration in the retail atypical antipsychotic market.

    Science.gov (United States)

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

    2010-03-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  16. Clozapine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan

    2014-01-01

    Background Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. Objectives To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. Selection criteria All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. Data collection and analysis We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) 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 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation

  17. Predicting Pharmacokinetic Stability by Multiple Oral Administration of Atypical Antipsychotics

    Science.gov (United States)

    Aoki, Kazuo; Sakiyama, Yojiro; Ohnishi, Takashi; Sugita, Makoto

    2013-01-01

    Lower fluctuation, i.e., lower peak-to-trough plasma-concentration variation at steady-state pharmacokinetics, has several advantages for the treatment of schizophrenia with antipsychotics. The reduction of peak concentration can decrease the risk of dose-dependent side effects, such as extrapyramidal symptom and somnolence, and by contrast the increase in trough concentration can decrease the incidence of lack of efficacy due to subtherapeutic drug concentration. Using a one-compartment simulation technique with pharmacokinetic parameters of each atypical antipsychotic collected from package inserts, the fluctuation index was calculated. Among the antipsychotics, the indices varied from 0.018 to 1.9, depending on dosing regimens, formulations and several pharmacokinetic properties. The order of simulated fluctuation index is active-moiety aripiprazole (b.i.d.) blonanserin (b.i.d.)

  18. Quetiapine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

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

  20. Asenapine, blonanserin, iloperidone, lurasidone, and sertindole: distinctive clinical characteristics of 5 novel atypical antipsychotics.

    Science.gov (United States)

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

    2013-01-01

    Schizophrenia is a serious, chronic, and devastating mental illness with a substantial impact on psychological, physical, social, and economical areas of an individual and society. To treat such critical mental illness, a number of first-generation (typical) and second-generation (atypical) antipsychotics are currently available in the market. Despite such treatment options, most of patients with schizophrenia have a poor treatment outcome and become treatment resistant, causing continual deterioration on positive, negative, and cognitive symptoms, resulting in impairment of socio-occupational functioning. Hence, additional novel antipsychotics with better efficacy, safety, and tolerability profiles are needed to enable clinicians to diversify treatment options to improve treatment of schizophrenia. Recently, the 3 antipsychotics, including iloperidone (2009), asenapine (2009), and lurasidone (2010), have been approved by the US Food and Drug Administration. Two other atypical antipsychotics, including sertindole and blonanserin, are approved and used outside the United States for treatment of schizophrenia. Sertindole, after it has been voluntarily suspended by the manufacturer in 1998 due to its potential risk in causing cardiovascular-related death, was relaunched to the European market in 2005. More recently, blonanserin was approved in Japan (2008) and in Korea (2009) for the management of schizophrenia. Individual antipsychotic may have differential pros and cons compared with other antipsychotic in terms of efficacy, safety, tolerability, restoration of functional capacity, and economic aspect reflecting relapse prevention. The purpose of this review was to provide distinctive clinical characteristics and up-to-date of clinical trial data of the 5 novel atypical antipsychotics for the management of schizophrenia, which may deliver clinicians better understanding in the use of such atypical antipsychotics for the treatment of schizophrenia in clinical

  1. Antipsychotic drug treatment in ambulatory dementia care: prevalence and correlates.

    Science.gov (United States)

    Eichler, Tilly; Wucherer, Diana; Thyrian, Jochen René; Kilimann, Ingo; Hertel, Johannes; Michalowsky, Bernhard; Teipel, Stefan; Hoffmann, Wolfgang

    2015-01-01

    The present study is the first to analyze primary data about the use of antipsychotic drugs among community dwelling people with dementia in German primary care. To determine (1) prevalence of antipsychotic drug treatment in German primary care patients who screened positive for dementia and (2) factors associated with antipsychotic drug treatment. DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western Pomerania) is an ongoing general practitioner-based, randomized, controlled intervention trial. A total of 4,064 community dwelling patients (≥70 years) recruited from 108 participating practices were screened for dementia (DemTect informed consent (59%). Present analyses are based on data of 243 patients who completed baseline assessment before January 2014 (preliminary data). Of the 243 patients who screened positive for dementia, a total of 25 patients (10%) received at least one antipsychotic drug. Atypical antipsychotic drugs (64%) were prescribed more often than typical antipsychotic drugs (36%). The results of the multivariate analysis showed that treatment by a specialist (neurologist/psychiatrist) was the only factor significantly associated with antipsychotic drug treatment (odds ratio, 12.86; p dementia living in nursing homes (>50%), the rate we found for community dwelling primary care patients who screened positive for dementia was low. Further research is needed to evaluate if these patients are adequately treated or if the antipsychotic drug treatment should and could be further reduced.

  2. Heterogeneous photocatalysis for selected atypical antipsychotic removal from river waters

    OpenAIRE

    Regulska, El?bieta; Karpi?ska, Joanna

    2011-01-01

    Heterogeneous photocatalysis of selected atypical antipsychotic, namely olanzapine, was examined. Photocatalytic degradation of above mentioned pharmaceutic was investigated in deionized and river water solution in the presence of titanium dioxide as a photocatalyst. River water samples were collected from Narew and Marycha, which run in the east of Poland. Studied irradiation sources included ultraviolet radiation and simulated solar light. Photodegradation efficiency and the presen...

  3. 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

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Correll Christoph

    2005-05-01

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

  6. Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management.

    Science.gov (United States)

    Levine, Michael; Ruha, Anne-Michelle

    2012-07-01

    Historically, treatment for schizophrenia focused on sedation. The advent of the typical antipsychotics resulted in treatment aimed specifically at the underlying disease, but these agents were associated with numerous adverse effects, and were not particularly effective at treatment of the negative symptoms of schizophrenia. As a result, numerous atypical agents have been developed over the past 2 decades, including several agents within the past 5 years. Overdose of antipsychotics remains quite common in Western society. In 2010, poison control centres in the US received nearly 43,000 calls related to atypical antipsychotics alone. Due to underreporting, the true incidence of overdose with atypical antipsychotics is likely much greater. Following overdose of an atypical antipsychotic, the clinical effects observed, such as CNS depression, tachycardia and orthostasis are largely predictable based on the unique receptor binding profile of the agent. This article, which focuses on the atypical antipsychotics commonly used in the treatment of schizophrenia, discusses the features commonly encountered in overdose. Specifically, agents that result in QT prolongation and the corresponding potential for torsades de pointes, as well as unique features encountered with the various medications are discussed. The diagnosis of this overdose is largely based on history. Routine use of drug screens is unlikely to be beneficial. The primary goal of management is aggressive supportive care. Patients with significant CNS depression with associated loss of airway reflexes and respiratory failure need advanced airway management. Hypotension should be treated first with intravenous fluids, with the use of direct acting vasopressors reserved for persistent hypotension. Benzodiazepines should be used for seizures, with barbiturates used for refractory seizures. Intravenous magnesium can be administered for patients with a corrected QT interval exceeding 500 milliseconds.

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

    Science.gov (United States)

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

    2017-08-09

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

  8. THE ROLE OF ATYPICAL ANTIPSYCHOTIC DECREASING AGGRESIVENESS IN SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    Juvita Novia Anggraini Maria

    2013-03-01

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

  9. Borderline personality disorder: bipolarity, mood stabilizers and atypical antipsychotics in treatment.

    Science.gov (United States)

    Belli, Hasan; Ural, Cenk; Akbudak, Mahir

    2012-10-01

    In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.

  10. Antipsychotic drug use and community-acquired pneumonia

    NARCIS (Netherlands)

    G. Trifirò (Gianluca)

    2011-01-01

    textabstractAntipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psychiatric disorders. In April 2005, the US Food and Drug Administration issued a warning about the increased risk of all-cause

  11. Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

    Science.gov (United States)

    Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

    2015-11-01

    Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Zuardi A.W.

    2006-01-01

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

  13. Intracellular modulation of NMDA receptor function by antipsychotic drugs.

    Science.gov (United States)

    Leveque, J C; Macías, W; Rajadhyaksha, A; Carlson, R R; Barczak, A; Kang, S; Li, X M; Coyle, J T; Huganir, R L; Heckers, S; Konradi, C

    2000-06-01

    The present study deals with the functional interaction of antipsychotic drugs and NMDA receptors. We show that both the conventional antipsychotic drug haloperidol and the atypical antipsychotic drug clozapine mediate gene expression via intracellular regulation of NMDA receptors, albeit to different extents. Data obtained in primary striatal culture demonstrate that the intraneuronal signal transduction pathway activated by haloperidol, the cAMP pathway, leads to phosphorylation of the NR1 subtype of the NMDA receptor at (897)Ser. Haloperidol treatment is likewise shown to increase (897)Ser-NR1 phosphorylation in rats in vivo. Mutation of (896)Ser and (897)Ser to alanine, which prevents phosphorylation at both sites, inhibits cAMP-mediated gene expression. We conclude that antipsychotic drugs have the ability to modulate NMDA receptor function by an intraneuronal signal transduction mechanism. This facilitation of NMDA activity is necessary for antipsychotic drug-mediated gene expression and may contribute to the therapeutic benefits as well as side effects of antipsychotic drug treatment.

  14. Combined serotonin (5-HT)1A agonism, 5-HT(2A) and dopamine D₂ receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats.

    Science.gov (United States)

    Oyamada, Yoshihiro; Horiguchi, Masakuni; Rajagopal, Lakshmi; Miyauchi, Masanori; Meltzer, Herbert Y

    2015-05-15

    Subchronic administration of an N-methyl-D-aspartate receptor (NMDAR) antagonist, e.g. phencyclidine (PCP), produces prolonged impairment of novel object recognition (NOR), suggesting they constitute a hypoglutamate-based model of cognitive impairment in schizophrenia (CIS). Acute administration of atypical, e.g. lurasidone, but not typical antipsychotic drugs (APDs), e.g. haloperidol, are able to restore NOR following PCP (acute reversal model). Furthermore, atypical APDs, when co-administered with PCP, have been shown to prevent development of NOR deficits (prevention model). Most atypical, but not typical APDs, are more potent 5-HT(2A) receptor inverse agonists than dopamine (DA) D2 antagonists, and have been shown to enhance cortical and hippocampal efflux and to be direct or indirect 5-HT(1A) agonists in vivo. To further clarify the importance of these actions to the restoration of NOR by atypical APDs, sub-effective or non-effective doses of combinations of the 5-HT(1A) partial agonist (tandospirone), the 5-HT(2A) inverse agonist (pimavanserin), or the D2 antagonist (haloperidol), as well as the combination of all three agents, were studied in the acute reversal and prevention PCP models of CIS. Only the combination of all three agents restored NOR and prevented the development of PCP-induced deficit. Thus, this triple combination of 5-HT(1A) agonism, 5-HT(2A) antagonism/inverse agonism, and D2 antagonism is able to mimic the ability of atypical APDs to prevent or ameliorate the PCP-induced NOR deficit, possibly by stimulating signaling cascades from D1 and 5-HT(1A) receptor stimulation, modulated by D2 and 5-HT(2A) receptor antagonism. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Trends in Scientific Literature on Atypical Antipsychotics in South Korea: A Bibliometric Study

    Science.gov (United States)

    Shen, Winston W.; Pae, Chi-Un; Moreno, Raquel; Rubio, Gabriel; Molina, Juan D.; Noriega, Concha; Pérez-Nieto, Miguel A.; Huelves, Lorena; Álamo, Cecilio

    2013-01-01

    Objective We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. Methods With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine, asenapine, iloperidone, lurasidone, perospirone and blonanserin. We applied some bibliometric indicators of paper production and dispersion with Price's law and Bradford's law, respectively. We also calculated the participation index (PI) of the different countries, and correlated the bibliometric data with some social and health data from Korea (such as total per capita expenditure on health and gross domestic expenditure on research and development). Results We collected 326 original papers published between 1993 and 2011. Our results state fulfilment of fulfilled Price's law, with scientific production on SGAs showing exponential growth (correlation coefficient r=0.8978, as against an r=0.8149 after linear adjustment). The most widely studied drugs were risperidone (91 papers), aripiprazole (77), olanzapine (53), and clozapine (43). Division into Bradford zones yielded a nucleus occupied by the Progress in Neuro-Psychopharmacology and Biological Psychiatry (36 articles). A total of 86 different journals were published, with 4 of the first 10 used journals having an impact factor being greater than 4. Conclusion The publications on SGAs in South Korea have undergone exponential growth over the studied period, without evidence of reaching a saturation point. PMID:23482954

  16. Methamphetamine psychosis, the efficacy of atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Amir Rezaei Ardani

    2014-12-01

    Full Text Available Worldwide growing methamphetamine abuse is one of the most serious health problems with several different consequences for victims, especially in developing countries. Chronic methamphetamine abuse is associated with several psychiatric problems in all countries which are faced to epidemic methamphetamine abuse. Methamphetamine-induced psychosis is a major medical challenge for clinical practitioner from both diagnostic and therapeutic viewpoints. Stimulant psychosis commonly occurs in people who abuse stimulants, but it also occurs in some patients taking therapeutic doses of stimulant drugs under medical supervision. The main characteristic of meth psychosis is the presence of prominent hallucinations and delusions. Other drugs, such as cocaine and marijuana, can trigger the onset of psychosis in someone who is already at increased risk because they have “vulnerability”.The current literature review attends to explain several aspects of MIP epidemiologically and clinically. Investigators proposed pharmacologically treatment based on recently published data.

  17. 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

  18. Psychotic and Bipolar Disorders: Antipsychotic Drugs.

    Science.gov (United States)

    Holder, Sarah D; Edmunds, Alaina L; Morgan, Sherri

    2017-04-01

    Antipsychotic drugs block dopamine receptors and are used to manage psychosis as well as other mental illnesses that may or may not have psychotic features, such as bipolar disorders and major depressive disorder. First-generation antipsychotic drugs are more likely to cause adverse effects such as extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second-generation antipsychotic drugs typically are related to metabolic abnormalities such as weight gain, abnormal blood glucose levels, and elevated lipid levels. Neuroleptic malignant syndrome is a rare but serious adverse effect of antipsychotic drugs that causes mental status changes, hyperthermia, and generalized rigidity. Timely diagnosis is essential due to a high risk of related morbidities if the syndrome remains untreated. Some adverse effects of antipsychotics can be identified and managed so that patients can continue beneficial therapy while minimizing the physiologic consequences. Patients taking antipsychotic drugs should be monitored regularly for adverse effects. Antipsychotics are also associated with potential drug interactions, the most lethal being prolongation of the QT interval, which can lead to fatal arrhythmias. Antipsychotic drugs can be used in special populations, such as pregnant women, children, and elderly patients, per recommendation from a mental health subspecialist. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    Sánchez-Moreno José

    2010-06-01

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

  1. Cognitive Impairment in Schizophrenia, Neurotransmitters and the New Atypical Antipsychotic Aripiprazole

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    Topolov Mariyan K.

    2016-03-01

    Full Text Available Cognition is a group of mental processes that includes the capacity to perceive, think, learn and to study, and the capacity of the brain to analyze information and program adaptive behaviour. Although there has been an appreciable evolution in the therapy of psychoses in the last twenty-five years, cognitive disturbances still persist in spite of antipsychotic treatment. The cognitive decay disrupts the ability of clinically diagnosed patients with psychoses, mainly schizophrenia, to learn and to memorize skills that are useful for their family and social relationships. Moreover, cognitive deficiency is often considered to be crucial for further rehabilitation. In atypical antipsychotics there are big differences in the effects on cognitive functions. Some clinical studies demonstrate the benefits of a third generation of antipsychotics on cognitive functions in patients treated for mental illnesses. In the present study we have reviewed many articles investigating the influence of aripiprazole on cognition in human and animal subjects. Aripiprazole is a third generation antipsychotic drug that possesses a unique pharmacodynamic profile, which in conjunction with recently published scientific data on the drugs’ influence on antidepressant, anxiolytic and cognitive functions, suggests a highly positive future potential for restorative cognitive treatment and ongoing healthy function. The data included in the review will contribute to determining the potential benefits of aripiprazole on memory and training processes.

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

    Science.gov (United States)

    Hauben, Manfred

    2004-09-01

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

  3. 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.

  4. Borderline personality disorder: bipolarity, mood stabilizers and atypical antipsychotics in treatment

    National Research Council Canada - National Science Library

    Belli, Hasan; Ural, Cenk; Akbudak, Mahir

    2012-01-01

    In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Neuroprotection of posttreatment with risperidone, an atypical antipsychotic drug, in rat and gerbil models of ischemic stroke and the maintenance of antioxidants in a gerbil model of ischemic stroke.

    Science.gov (United States)

    Yan, Bing Chun; Park, Joon Ha; Ahn, Ji Hyeon; Kim, In Hye; Park, Ok Kyu; Lee, Jae-Chul; Yoo, Ki-Yeon; Choi, Jung Hoon; Lee, Choong Hyun; Hwang, In Koo; Park, Jeong Ho; Her, Song; Kim, Jin Su; Shin, Hyung-Cheul; Cho, Jun Hwi; Kim, Young-Myeong; Kwon, Seung-Hae; Won, Moo-Ho

    2014-06-01

    Risperidone, an atypical antipsychotic drug, has been discovered to have some beneficial effects beyond its original effectiveness. The present study examines the neuroprotective effects of risperidone against ischemic damage in the rat and gerbil induced by transient focal and global cerebral ischemia, respectively. The results showed that pre- and posttreatment with 4 mg/kg risperidone significantly protected against neuronal death from ischemic injury. Many NeuN-immunoreactive neurons and a few F-J B-positive cells were found in the rat cerebral cortex and gerbil hippocampal CA1 region (CA1) in the risperidone-treated ischemia groups compared with those in the vehicle-treated ischemia group. In addition, treatment with risperidone markedly attenuated the activation of microglia in the gerbil CA1. On the other hand, we found that treatment with risperidone significantly maintained the antioxidants levels in the ischemic gerbil CA1. Immunoreactivities of superoxide dismutases 1 and 2, catalase, and glutathione peroxidase were maintained in the stratum pyramidale of the CA1; the antioxidants were very different from those in the vehicle-treated ischemia groups. In brief, our present findings indicate that posttreatment as well as pretreatment with risperidone can protect neurons in the rat cerebral cortex and gerbils CA1 from transient cerebral ischemic injury and that the neuroprotective effect of risperidone may be related to attenuation of microglial activation as well as maintenance of antioxidants. Copyright © 2014 Wiley Periodicals, Inc.

  7. 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

  8. Impact of atypical antipsychotic use among adolescents with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Sikirica, Vanja; Pliszka, Steven R; Betts, Keith A; Hodgkins, Paul; Samuelson, Thomas M; Xie, Jipan; Erder, M Haim; Dammerman, Ryan S; Robertson, Brigitte; Wu, Eric Q

    2014-09-01

    To compare treatment patterns, resource utilization, and costs to US third-party payers of stimulant-treated adolescent attentiondeficit/ hyperactivity disorder (ADHD) patients who switched to or augmented with atypical antipsychotics (AAPs; not FDA-indicated for ADHD) with those who switched to or augmented with nonantipsychotic medications. Retrospective cohort study conducted using a US commercial medical/pharmacy claims database. Adolescent patients with an ADHD diagnosis and ≥ 1 stimulant medication claim between January 2005 and December 2009 were identified. Patients were classified into the AAP or non-antipsychotic cohorts based on subsequent claims for AAPs or non-antipsychotic medications, respectively. Patients with psychiatric diagnoses for which AAPs are often prescribed were excluded. Patients were matched 1:1 from the AAP to the non-antipsychotic cohort using propensity score matching. Treatment patterns, resource utilization, and costs in the 12 months after AAP or non-antipsychotic initiation were compared using Cox models, Poisson regression, and Wilcoxon signed-rank tests, respectively. After propensity score matching, a total of 849 adolescents were included in each of the matched cohorts. Patients in the AAP cohort had a significantly higher rate of medication augmentation (27.7% vs 15.5%; hazard ratio = 2.56; 95% confidence interval [CI], 1.90-3.46; P < .001) than patients in the non-antipsychotic cohort. The AAP cohort also had significantly higher incidences of inpatient admissions (0.13 vs 0.05; incidence rate ratio [IRR] = 2.45; 95% CI, 1.73-3.48; P < .001), emergency department visits (0.39 vs 0.31; IRR = 1.27; 95% CI, 1.08-1.49; P = .004), and outpatient visits (14.82 vs 13.19; IRR = 1.12; 95% CI, 1.10-1.15; P < .001), and incurred significantly higher mean annual medical ($3622 vs $3311; P = .002), drug ($4314 vs $2884; P < .001), and total healthcare ($7936 vs $6195; P < .001) costs. Stimulant-treated adolescents with ADHD who

  9. 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

  10. Utilización de Neurolépticos atípicos en el Centro Penitenciario de Málaga Study of the use of atypical antipsychotic drugs in Málaga Prison

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    C. Salinas Rosillo

    2007-06-01

    . Materials and Methods: A retrospective study was carried out on the use of antipsychotic drugs from 2003 to 2004 in Malaga State Prison. A comparison was then made with the use of this type of medication in the Primary Health Care District of Guadalhorce. Data on medication consumption was taken from medical orders received at the prison during this study. The ATC (Anatomical Therapeutic and Chemical Classifying System was used for classifying the active principles. The prison"s own data base (SANIT was used for calculating the number of containers. For calculating the DDD, the ratio DDD/1000 inmates/day was utilised. Results: The use of atypical antipsychotic medication in the prison increased. There is an increasing trend towards the use of quetiapine in small doses. The use of risperidone went down during the period of this study, although it is still the most commonly used drug in DDD and in consumed containers. The Primary Health care results indicate a trend in the opposite direction. Conclusion: The use of the group of drugs in this study has decreased in the Primary Health Care area, possibly because of special medical control measures such as the control stamp. In Malaga Prison use of these drugs has increased. The reasons for this difference are as yet unknown.

  11. Effect of novel atypical antipsychotic, blonanserin, on extracellular neurotransmitter level in rat prefrontal cortex.

    Science.gov (United States)

    Ohoyama, Keiko; Yamamura, Satoshi; Hamaguchi, Tatsuya; Nakagawa, Masanori; Motomura, Eishi; Shiroyama, Takashi; Tanii, Hisashi; Okada, Motohiro

    2011-02-25

    To clarify the mechanisms of action of blonanserin, an atypical antipsychotic drug, we studied the effects of systemic administration of blonanserin and risperidone on extracellular levels of norepinephrine, dopamine, serotonin, GABA and glutamate in the medial prefrontal cortex using microdialysis, and neuronal firing in the ventral tegmental area, locus coeruleus, dorsal raphe nucleus and mediodorsal thalamic nucleus using radiotelemetry. The binding affinities of blonanserin to D(2) and 5-HT(2A) receptors in the rat brain were confirmed and found to be similar. Blonanserin transiently increased neuronal firing in locus coeruleus and ventral tegmental area but not in dorsal raphe nucleus or mediodorsal thalamic nucleus, whereas risperidone increased the firing in locus coeruleus, ventral tegmental area and dorsal raphe nucleus but not in mediodorsal thalamic nucleus. Blonanserin persistently increased frontal extracellular levels of norepinephrine and dopamine but not serotonin, GABA or glutamate, whereas risperidone persistently increased those of norepinephrine, dopamine and serotonin but not GABA or glutamate. These results suggest a pharmacological correlation between the stimulatory effects of these antipsychotics on frontal monoamine release and neuronal activity in monoaminergic nuclei. Inhibition of the α(2) adrenoceptor increased extracellular monoamine levels and enhanced blonanserin-induced increase in extracellular serotonin level. These results indicated that the combination of antagonism of D(2) and 5-HT(2A) receptors contribute to the rise in extracellular levels of norepinephrine and dopamine, and that α(2) adrenoceptors play important roles in frontal serotonin release. They also suggest that blonanserin-induced activation of monoaminergic transmission could be, at least partially, involved in atypical antipsychotic properties of blonanserin. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Effects of atypical (risperidone) and typical (haloperidol) antipsychotic agents on astroglial functions.

    Science.gov (United States)

    Quincozes-Santos, André; Bobermin, Larissa Daniele; Tonial, Rafaela Pestana Leques; Bambini-Junior, Victorio; Riesgo, Rudimar; Gottfried, Carmem

    2010-09-01

    Although classical and atypical antipsychotics may have different neurotoxic effects, their underlying mechanisms remain to be elucidated, especially regarding neuroglial function. In the present study, we compared the atypical antipsychotic risperidone (0.01-10 μM) with the typical antipsychotic haloperidol (0.01-10 μM) regarding different aspects such as glutamate uptake, glutamine synthetase (GS) activity, glutathione (GSH) content, and intracellular reactive oxygen species (ROS) production in C6 astroglial cells. Risperidone significantly increased glutamate uptake (up to 27%), GS activity (14%), and GSH content (up to 17%). In contrast, haloperidol was not able to change any of these glial functions. However, at concentration of 10 μM, haloperidol increased (12%) ROS production. Our data contribute to the clarification of different hypothesis concerning the putative neural responses after stimulus with different antipsychotics, and may establish important insights about how brain rewiring could be enhanced.

  13. Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.

    Science.gov (United States)

    Kose, Eiji; Uno, Kana; Hayashi, Hiroyuki

    2017-01-01

     Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.

  14. Managing risk when considering the use of atypical antipsychotics for elderly patients with dementia-related psychosis.

    Science.gov (United States)

    Recupero, Patricia R; Rainey, Samara E

    2007-05-01

    In 2005, responding to several studies, the FDA issued a black box warning on atypical (second generation) antipsychotic medications, noting that the drugs may increase the risk of cerebrovascular adverse events in elderly patients with dementia-related behavior disturbances. The black box warning has raised concern for clinicians, among whom atypical antipsychotics have gained favor for having a more tolerable side-effect profile than many other pharmacological treatment options. Complicating this concern are studies suggesting that other medications may have similar risks and a dearth of unbiased head-to-head studies comparing different treatment options. To effectively manage risk when treating elderly patients with dementia-related psychosis, physicians, patients, and caregivers must consider both acute risks (such as danger of bodily harm to the patient and others) and long-term risks (such as placement in a restrictive nursing home). If an atypical antipsychotic is chosen, additional risk management may be warranted. This paper presents a brief overview of relevant concerns and suggests some techniques to help minimize and manage risk, such as increased monitoring, informed consent, and thorough documentation. A sample clinical risk management form and a sample letter to the primary care physician are provided to help guide clinicians in improving their risk management practices when working with elderly patients suffering from dementia-related psychosis and related behavioral difficulties.

  15. Management of psychiatric disorders in children and adolescents with atypical antipsychotics: a systematic review of published clinical trials.

    NARCIS (Netherlands)

    Jensen, P.S.; Buitelaar, J.K.; Pandina, G.J.; Binder, C.; Haas, M. de

    2007-01-01

    We aimed to provide a descriptive review of treatment studies of atypical antipsychotics in paediatric psychiatric disorders. A systematic review of the literature used Medline and EMBASE databases to identify clinical trials of atypical antipsychotics in children and adolescents between 1994 and

  16. Tardive dyskinesia in patients treated with atypical antipsychotics: case series and brief review of etiologic and treatment considerations

    Directory of Open Access Journals (Sweden)

    Jungjin Kim

    2014-04-01

    Full Text Available Tardive dyskinesia (TD is a disfiguring side-effect of antipsychotic medications that is potentially irreversible in affected patients. Newer atypical antipsychotics are felt by many to have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report five cases of patients taking atypical antipsychotics who developed TD, review the risk of TD, its potential etiologic mechanisms, and treatment options available. The goal of this paper is to alert the reader to continue to be diligent in obtaining informed consent and monitoring for the onset of TD in patients taking atypical antipsychotics.

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

    African Journals Online (AJOL)

    Participants were recruited randomly and intermittently until a sample size of 217 was attained. Data on the use of herbal medicines, type of antipsychotic drug, compliance with dosage regimen, duration of antipsychotic therapy, side effects of antipsychotic drugs and some socio-demographic characteristics were collected ...

  18. [Prevention and treatment of tardive dyskinesia caused by antipsychotic drugs].

    Science.gov (United States)

    Seigneurie, A-S; Sauvanaud, F; Limosin, F

    2016-06-01

    Tardive dyskinesia (TD) is a movement disorder of tongue, jawbone, trunk and/or limbs that may appear after a prolonged use of dopamine receptor blocking agents (after 3 months of treatment or after 1 month for patients over 60), and that are present during at least four consecutive weeks. TD is a frequent side effect of both classical neuroleptics and new generation antipsychotic drugs. The prevalence of iatrogenic TD is between 24 and 32 % after treatment with classical neuroleptics and about 13 % after treatment with a new generation antipsychotic. This paper presents an updated literature review of data on diagnosis, prevention and treatment of TD. We conducted a review of literature using the Medline Browser tool, screening studies from 1950 to 2013 in English or French with keywords « tardive dyskinesia », « tardive dystonia », and « abnormal movements caused by antipsychotic drugs ». We first describe and define semeiological features of TD: dystonia, tremor, myoclonus, acathisie, chorea, ballism and athetosia. Secondarily, we resume the main differential diagnoses to exclude when confronted with this kind of movement disorders. Differential diagnoses for dyskinesia can be classified between primary (Parkinson and Huntington diseases) and secondary (Wilson disease, intoxication, metabolic abnormality, cerebrovascular accident) abnormal movements. Psychogenic TD can be evocated if previous pathologies are excluded in case of atypical clinical presentation. We detail the risk factors for TD. Endogenous risk factors are related to the patient's age, underlying psychiatric disease (bipolar disorder or Alzheimer dementia), addiction to alcohol or cocaine, female gender, or neurodevelopmental vulnerability. Iatrogenic risk factors are high doses of antipsychotics, long or intermittent administration, and particular pharmaceutical classes or associations of antipsychotics. As a comprehensive tool, we review the main physiopathological hypotheses to

  19. Monitoring Metabolic Side Effects of Atypical Antipsychotics in People with an Intellectual Disability

    Science.gov (United States)

    Teeluckdharry, Sadira; Sharma, Sujit; O'Rourke, Elizabeth; Tharian, Priyanka; Gondalekar, Anjali; Nainar, Feroz; Roy, Meera

    2013-01-01

    This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of…

  20. Atypical antipsychotic-like effects of the dopamine D-3 receptor agonist, (+)-PD 128,907

    NARCIS (Netherlands)

    Witkin, J; Gasior, M; Acri, J; Beekman, M; Thurkauf, A; de Boer, Peter; Wikstrom, H; Dijkstra, D

    1998-01-01

    Anti-schizophrenia agents with improved efficacy and side-effect profiles are required. A dopamine D-3 receptor agonist, R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol HCl ((+)-PD 128,907), displayed an atypical antipsychotic profile comparable to that of

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

    Science.gov (United States)

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

    2012-01-01

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

  2. Risk of hospitalization for acute pancreatitis associated with conventional and atypical antipsychotics: a population-based case-control study

    DEFF Research Database (Denmark)

    Gasse, Christiane; Jacobsen, Jacob; Pedersen, Lars

    2008-01-01

    as the index date for the matched control subjects. Conditional logistic regression analysis was used to estimate rate ratios (RRs) for hospitalization due to acute pancreatitis in current users (0-90 days before admission or index date) and former users (> 90 days before admission or index date) of atypical...... for current use and former use of atypical antipsychotics were 0.6 (95% confidence interval [CI] 0.3-1.1) and 0.3 (95% CI 0.1-0.9), respectively. A trend was noted for increasing risk of hospitalization due to acute pancreatitis with decreasing potency of conventional antipsychotics, with adjusted RRs of 1...... and conventional antipsychotics compared with nonusers of the respective antipsychotics, while controlling for covariates and stratifying by age. Fifteen case patients (0.5%) were current users of atypical antipsychotics, and 128 case patients (4.2%) were current users of conventional antipsychotics. Adjusted RRs...

  3. Patients' attitudes towards generic substitution of oral atypical antipsychotics: a questionnaire-based survey in a hypothetical pharmacy setting.

    Science.gov (United States)

    Roman, Beatriz

    2009-08-01

    Generic atypical antipsychotics in tablet form differ in name, appearance and packaging from the innovator brand antipsychotics. These differences might cause anxiety, confusion and misperceptions in some ambulant patients with psychoses/schizophrenia, especially if the brand atypical antipsychotic is substituted in the pharmacy without the acknowledgement of the patient and treating psychiatrist. Furthermore, generic substitution of branded oral atypical antipsychotics in the pharmacy might cause nonadherence and potentially lead to suboptimal treatment outcomes if patients perceive the medicines to be clinically different. To determine the attitudes of patients with psychoses/schizophrenia towards generic substitution of oral atypical antipsychotics in a pharmacy setting. A total of 106 ambulant patients with psychoses/schizophrenia currently taking an oral atypical antipsychotic (risperidone [Risperdal], olanzapine [Zyprexa], quetiapine [Seroquel] or aripiprazole [Abilify]) were confronted with generic substitution in a hypothetical pharmacy setting.Two conditions were used: one granting patients a short explanation about the substitution, and one without explanation. Patients' attitudes towards the generic substitution were assessed using a combined quantitative and qualitative design. Of the respondents, 73% stated that they would be unlikely to take a generic antipsychotic if their pharmacist were to substitute it. Providing patients with a short explanation had a significantly positive effect on their intention to take a generic version; however, overall, the patients' intention to take the generic antipsychotic lay well below a neutral midpoint. Patients with psychoses/schizophrenia using atypical antipsychotics in tablet form perceive generic versions of their antipsychotics as being significantly different. This perceived difference lowers their intention of continuing to take the medication, thus possibly jeopardizing treatment outcome. Caution with the

  4. Blonanserin, a novel atypical antipsychotic agent not actively transported as substrate by P-glycoprotein.

    Science.gov (United States)

    Inoue, Tomoko; Osada, Kenichi; Tagawa, Masaaki; Ogawa, Yuriko; Haga, Toshiaki; Sogame, Yoshihisa; Hashizume, Takanori; Watanabe, Takashi; Taguchi, Atsushi; Katsumata, Takashi; Yabuki, Masashi; Yamaguchi, Noboru

    2012-10-01

    Although blonanserin, a novel atypical antipsychotic agent with dopamine D(2)/serotonin 5-HT(2A) antagonistic properties, displays good brain distribution, the mechanism of this distribution has not been clarified. P-glycoprotein [(P-gp) or multidrug resistance protein 1 (MDR1)] is an efflux transporter expressed in the brain and plays an important role in limiting drug entry into the central nervous system (CNS). In particular, P-gp can affect the pharmacokinetics and efficacy of antipsychotics, and exacerbate or soothe their adverse effects. In this study, we conducted in vitro and in vivo experiments to determine whether blonanserin is a P-gp substrate. Risperidone and its active metabolite 9-hydroxyrisperidone, both of which are P-gp substrates, were used as reference drugs. Affinity of blonanserin, risperidone, and 9-hydroxyrisperidone for P-gp was evaluated by in vitro transcellular transport across LLC-PK1, human MDR1 cDNA-transfected LLC-PK1 (LLC-MDR1), and mouse Mdr1a cDNA-transfected LLC-PK1 (LLC-Mdr1a). In addition, pharmacokinetic parameters in the brain and plasma (B/P ratio) of test compounds were measured in mdr1a/1b knockout (KO) and wild-type (WT) mice. The results of in vitro experiments revealed that P-gp does not actively transport blonanserin as a substrate in humans or mice. In addition, blonanserin displayed comparable B/P ratios in KO and WT mice, whereas B/P ratios of risperidone and 9-hydroxyrisperidone differed markedly in these animals. Our results indicate that blonanserin is not a P-gp substrate and therefore its brain distribution is unlikely to be affected by this transporter. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-11-01

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

  6. Evidenced-based pharmacologic treatment of borderline personality disorder: a shift from SSRIs to anticonvulsants and atypical antipsychotics?

    Science.gov (United States)

    Abraham, P Francis; Calabrese, Joseph R

    2008-11-01

    The authors performed a review of double-blind, controlled studies of psychotropic drugs to evaluate the evidence base supporting their use in treatment of borderline personality disorder. English language literature cited in Medline and published between 1970 and 2006 was searched using the following terms: anticonvulsants, antidepressants, antipsychotics, anxiolytics, benzodiazepines, borderline personality disorder, lithium, medication, mood stabilizers, pharmacotherapy, and psychotropics. Only reports of double-blind, randomized, controlled trials were included. Twenty eight double-blind, randomized, controlled trials were identified which included anticonvulsants, classical neuroleptics, the benzodiazepine alprazolam, lithium, monoamine oxidase inhibitors, the novel antipsychotic olanzapine, selective serotonin reuptake inhibitors, tricyclic antidepressants, and omega-3 fatty acids. All but three were placebo-controlled. With the exception of alprazolam and tricyclics, the data from these trials revealed evidence of improvements, although often circumscribed and variable. The novel antipsychotic olanzapine appeared to have the most empirical support for having a favorable effect on borderline personality disorder. A growing body of data suggests that there are psychotropic agents which appear to be well tolerated, and which to varying degrees may be expected to ameliorate the domains of psychopathology associated with borderline personality disorder. The research literature, on which practice should be optimally based, appears to suggest a need for a shift from antidepressants to anticonvulsants and atypical antipsychotics.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Serum prolactin levels and sexual dysfunctions in antipsychotic medication, such as risperidone : a review

    NARCIS (Netherlands)

    Knegtering, H; Lambers, PA; Prakken, G; ten Brink, C

    Classical antipsychotic drugs increase the level of serum prolactin. The atypical antipsychotic clozapine barely increases prolactin levels. An open naturalistic study in the University Hospital of Groningen suggests that treatment with risperidone in comparison to classical antipsychotics seems to

  9. [Evolution of antipsychotic drug consumption in the autonomous community of Castile and Leon, Spain (1990-2001)].

    Science.gov (United States)

    García del Pozo, Javier; Isusi Lomas, Laura; Carvajal García-Pando, Alfonso; Martín Rodríguez, Igor; Sáinz Gil, María; García del Pozo, Victorina; Velasco Martín, Alfonso

    2003-01-01

    Over the past ten years, new drugs and new approaches to treatment have been implemented making it possible to assume changes in the use of antipsychotic drugs in our environment. This study is aimed at characterizing the pattern of use of antipsychotic drugs in Castile and Leon throughout the 1990-2001 period as well as ascertaining the bearing which the marketing of new antipsychotic drugs may have had on the pattern of consumption of these drugs. The drug consumption data was obtained from the Ministry of Health and Consumer Affairs' consumption database ECOM (Especialidades Consumo de Medicamentos). This database contains information on the consumption of medications dispensed charged to the Social Insurance system in community pharmacies nationwide. To estimate the consumption outside of the National Health System, data from the IMS (International Marketing Services) firm for the years 2000 and 2001 was used. The data was given in Defined Daily Doses/1000 inhabitants/day. The use of antipsychotic drugs rose by 146% within the 1990-2001 period. Throughout the period studied, haloperidol was the antipsychotic drug most used in Spain and in Castile and Leon. The atypical antipsychotic drugs totaled 49% of the total consumption for 2001 and 90% of the costs, a strong trend being found toward an increase in the consumption of these atypical antipsychotic drugs in detriment to the typical antipsychotic drugs. It has been estimated that 14% of the antipsychotic drugs used in Castile and Leon were used outside of the National Health System.. Appreciable differences exist among the different provinces. The consumption of antipsychotic drugs in Castile and Leon grew by 146% throughout the twelve months studied. The marketing of new atypical antipsychotic drugs and the legal measures related to the deinstitutionalization of mental patients may have played a major role in this increase. The marketing of the new antipsychotic drugs has led to a change in their pattern of

  10. Clinical Assessment of Weight Gain with Atypical Antipsychotics - Blonanserin vs Amisulpride.

    Science.gov (United States)

    Deepak, T S; Raveesh, B N; Parashivamurthy, B M; Kumar, Ms Narendra; Majgi, Sumanth Mallikarjuna; Nagesh, H N

    2015-06-01

    Atypical antipsychotics appear to have the greatest potential to induce weight gain. Antipsychotic-induced weight gain is the one of main cause of non-compliance and discontinuation of treatment, often resulting in the relapse of psychosis. To compare the weight gain between amisulpride and blonanserin treatment, in persons with psychosis. Fifty six subjects with psychosis attending psychiatry department at KR Hospital, Mysore were randomized into two equal groups. After obtaining informed consent, subjects of group I received amisulpride tablets 200 mg BD, and group II received blonanserin tablets 4 mg BD, for eight weeks. Body weight, Body Mass Index (BMI) and Waist Hip Ratio (WHR) were measured at baseline, 4 weeks and 8 weeks. The mean weight gain with amisulpride at 4 weeks was 2.73 kg (5.21%) and at 8 weeks was 4.34 kg (8.28%) from the baseline. The mean weight gain with blonanserin at 4 weeks was 1.77 kg (3.46%) and at 8 weeks was 3.46 kg (6.75%) from the baseline. The mean BMI increase at 8 weeks with amisulpride was 1.66 ± 0.56 and with blonanserin was 1.34 ± 0.77. The mean WHR increase at 8 weeks with amisulpride was 0.036 ± 0.026 and with blonanserin was 0.029 ± 0.020. There was statistically significant increase in weight, BMI and WHR associated with both blonanserin and amisulpride at 8 weeks. But there was no statistically significant difference in those parameters between blonanserin and amisulpride, at eight weeks. Even though there was no significant difference in the weight gain caused by blonanserin, in comparison with amisulpride, both these drugs individually caused significant weight gain at 8 weeks, which is in contrast with the earlier studies, which needs to be further evaluated.

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

    Directory of Open Access Journals (Sweden)

    Maurizio Pompili

    2016-10-01

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

  12. Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

    Science.gov (United States)

    Park, Young-Min; Lee, Seung-Hwan; Lee, Bun-Hee; Lee, Kyu Young; Lee, Kye-Seong; Kang, Seung-Gul; Lee, Hwa-Young; Kim, Won

    2016-05-30

    The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (p<0.01). Moreover, there was a strong positive correlation between serum levels of prolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-08

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

  14. Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

    Directory of Open Access Journals (Sweden)

    Joseph McEvoy

    Full Text Available There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group, 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group, and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs, including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.

  15. Atypical Antipsychotics and the Risk of Hyperlipidemia: A Sequence Symmetry Analysis.

    Science.gov (United States)

    Takeuchi, Yoshinori; Kajiyama, Kazuhiro; Ishiguro, Chieko; Uyama, Yoshiaki

    2015-07-01

    Although hyperlipidemia is a well known adverse event of atypical antipsychotic (AAP) medication, there are few studies that have quantitatively compared the risks of various AAPs. Our aim was to comparatively evaluate the risk of hyperlipidemia associated with the use of AAPs approved in Japan through a consecutive epidemiological study. We conducted a sequence symmetry analysis (SSA) using health insurance claims data to analyze the following nine AAPs approved for use in Japan: risperidone, paliperidone, perospirone hydrochloride hydrate, blonanserin, clozapine, olanzapine, quetiapine fumarate, aripiprazole, and zotepine. Exposed cases were identified from drug dispensing records as those who had been administered both AAPs and antihyperlipidemic drugs. The adjusted sequence ratio (ASR) and 95 % confidence interval (CI) for each individual AAP and for all AAPs were calculated while controlling for time trends in dispensing patterns. Olanzapine was significantly associated with increased hyperlipidemia occurrence (ASR 1.56; 95 % CI 1.25-1.95). The ASRs obtained for risperidone (1.01; 95 % CI 0.80-1.27), perospirone hydrochloride hydrate (0.93; 95 % CI 0.63-1.39), blonanserin (0.83; 95 % CI 0.52-1.33), quetiapine fumarate (0.93; 95 % CI 0.73-1.18), and aripiprazole (1.02; 95 % CI 0.82-1.26) were approximately 1.0. Unstable estimates (wide CIs) were obtained for paliperidone and zotepine due to the small sample sizes. Among the AAPs used in Japan, only olanzapine was found to have an elevated risk of hyperlipidemia. In contrast, risperidone, perospirone hydrochloride hydrate, blonanserin, quetiapine fumarate, and aripiprazole had relatively low risks.

  16. Are specific initiatives required to enhance prescribing of generic atypical antipsychotics in Scotland?: International implications.

    Science.gov (United States)

    Bennie, M; Bishop, I; Godman, B; Barbui, C; Raschi, E; Campbell, S; Miranda, J; Gustafsson, L L

    2013-02-01

    National and regional authorities in Scotland have introduced multiple measures to appreciably enhance prescribing efficiency for the proton pump inhibitors (PPIs), statins and renin-angiotensin inhibitor drugs. Generic oral risperidone recently became available in Scotland; however, schizophrenia is a complex disease with advice from respected authorities suggesting that treatment should be individualised. To assess (i) changes in atypical antipsychotic drug (AAP) utilisation and expenditure following the availability of oral generic risperidone in Scotland; (ii) to determine (a) current INN prescribing rates for risperidone following generic availability and (b) decrease in expenditure/DDD for generic risperidone; (iii) to suggest additional measures that could possibly be introduced in Scotland to further enhance prescribing of generic AAPs; and (iv) to provide guidance to NHS Scotland as well as other European authorities on the implications. Retrospective observational study and an interrupted time series design. No appreciable change in the utilisation patterns of risperidone pre- and postgeneric availability. Appreciable INN prescribing averaged 93-98% of total oral risperidone. Generic risperidone was 84% below prepatent loss prices by study end, reducing annual expenditure for oral risperidone in 2010 by GB£3.19mn compared with prepatent loss situation. However, overall expenditure on AAPs increased by 42% from 2005 to 2010. As expected, there was no change in utilisation patterns for risperidone, although potential to influence prescribing patterns. Continued high INN prescribing suggests no problems with generic risperidone in practice. Costs will start to decrease as more AAPs lose their patents (olanzapine and quetiapine). There is the possibility to accelerate this reduction through educational activities. There is potential to realise some savings with generic AAPs. However, this is limited by the complexity of the disease area. Any measures

  17. Liver function tests during treatment with antipsychotic drugs: a case series of 23 patients.

    Science.gov (United States)

    Mouradian-Stamatiadis, Laurence; Dumortier, Gilles; Januel, Dominique; Delmas, Beatrice Aubriot; Cabaret, Wanda

    2002-12-01

    Atypical antipsychotics represent a new class of medication for the treatment of schizophrenia and their use is associated with a reduction of neurological side effects. This article reports the result of the systematic clinical and biological supervision of hepatic enzymes on 23 schizophrenic inpatients treated by atypical antipsychotic during 2 weeks at Days 1 (D1), 7 (D7), and 14 (D14) in a naturalistic study during 6 months. The drug administrated was limited to four medications--risperidone, amisulpride, olanzapine, and clozapine--but other psychotropic agents were prescribed. Six cases of biological cytolytic hepatitis were observed. Due to the numerous risk factors and the frequency of "routine" conditions, careful supervision of the hepatic function is needed to prevent this kind of side effect.

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

    Science.gov (United States)

    Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

    2010-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Grošić V

    2014-07-01

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

  20. Atypical antipsychotic properties of blonanserin, a novel dopamine D2 and 5-HT2A antagonist.

    Science.gov (United States)

    Ohno, Yukihiro; Okano, Motoki; Imaki, Junta; Tatara, Ayaka; Okumura, Takahiro; Shimizu, Saki

    2010-08-01

    Blonanserin is a novel antipsychotic agent that preferentially interacts with dopamine D(2) and 5-HT(2A) receptors. To assess the atypical properties of blonanserin, we evaluated its propensity to induce extrapyramidal side effects (EPS) and to enhance forebrain Fos expression in mice. The actions of AD-6048, a primary metabolite of blonanserin, in modulating haloperidol-induced EPS were also examined. Blonanserin (0.3-10mg/kg, p.o.) did not significantly alter the pole-descending behavior of mice in the pole test or increase the catalepsy time, while haloperidol (0.3-3mg/kg, p.o.) caused pronounced bradykinesia and catalepsy. Blonanserin and haloperidol at the above doses significantly enhanced Fos expression in the shell (AcS) region of the nucleus accumbens and dorsolateral striatum (dlST). The extent of blonanserin-induced Fos expression in the AcS was comparable to that induced by haloperidol. However, the striatal Fos expression by blonanserin was less prominent as compared to haloperidol. Furthermore, combined treatment of AD-6048 (0.1-3mg/kg, s.c.) with haloperidol (0.5mg/kg, i.p.) significantly attenuated haloperidol-induced bradykinesia and catalepsy. The present results show that blonanserin behaves as an atypical antipsychotic both in inducing EPS and enhancing forebrain Fos expression. In addition, AD-6048 seems to contribute at least partly to the atypical properties of blonanserin. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Head-to-head comparison of the costs of atypical antipsychotics: a systematic review.

    Science.gov (United States)

    Barbui, Corrado; Lintas, Camilla; Percudani, Mauro

    2005-01-01

    In many countries, prescribing guidelines recommend the use of atypical or second-generation antipsychotics (SGAs) in the first-line treatment of individuals with newly diagnosed schizophrenia. This recommendation has increased the utilisation of these agents and, consequently, produced a progressive increase in the proportion of total direct costs in schizophrenia accounted for by drug therapy. In this still-evolving context of care, it becomes relevant to critically investigate the literature base on the relative cost effectiveness of each SGA in comparison with the others, the purpose being to ascertain whether the data reveal any one agent to be truly more cost effective than the others.A systematic search of economic evaluations comparing two or more SGAs yielded 19 studies meeting the inclusion criteria. Of these, 11 were retrospective database or chart review analyses, six were observational prospective or mirror-image studies, and two were randomised clinical trials. Olanzapine and risperidone were compared in 16 studies, two studies compared clozapine, olanzapine and risperidone, and one compared clozapine and risperidone. While experimental studies indicated an absence of differences among the SGAs in terms of total expenditure, database analyses found contrasting evidence. These latter studies, although susceptible to bias and confounding, should theoretically provide an added dimension, in that they are based on observations from 'real world' practice. However, there were too many potential threats to the validity of these analyses to draw a firm conclusion that any one agent is truly more cost effective than the others. In this uncertain situation, clinicians and policy makers should be aware that indirect evidence from independent randomised controlled trials comparing individual SGAs with haloperidol suggested similar cost effectiveness. As healthcare providers in different settings are ultimately the ones who pay for new innovations, it seems

  2. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes.

    Science.gov (United States)

    Spielmans, Glen I; Berman, Margit I; Linardatos, Eftihia; Rosenlicht, Nicholas Z; Perry, Angela; Tsai, Alexander C

    2013-01-01

    Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk-benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48-2.73), OFC (OR, 1.42; 95% CI, 1.01-2.0), quetiapine (OR, 1.79; 95% CI, 1.33-2.42), and risperidone (OR, 2.37; 95% CI, 1.31-4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58-2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87-1.93), quetiapine (OR, 1.53, 95% CI, 1.17-2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16-2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery-Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g = 0.49). Treatment was linked to several adverse

  3. Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes

    Science.gov (United States)

    Spielmans, Glen I.; Berman, Margit I.; Linardatos, Eftihia; Rosenlicht, Nicholas Z.; Perry, Angela; Tsai, Alexander C.

    2013-01-01

    Background Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk–benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. Methods and Findings We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48–2.73), OFC (OR, 1.42; 95% CI, 1.01–2.0), quetiapine (OR, 1.79; 95% CI, 1.33–2.42), and risperidone (OR, 2.37; 95% CI, 1.31–4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58–2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87–1.93), quetiapine (OR, 1.53, 95% CI, 1.17–2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16–2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery–Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. OBJECTIVE......: 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...

  5. Pharmacoeconomic study of antipsychotic drugs in India

    OpenAIRE

    S. Nagaraja Prasad; Vedavathi H.

    2017-01-01

    Background: Schizophrenia is a disorder of relatively high point prevalence, low incidence and high disability. It accounts for nearly 1.5-3% of total national expenditure on health care. There is a gross variation in the cost of various branded and generic versions of antipsychotics available in India. This can lead to decreased patient compliance. The present study was undertaken to highlight this variation in the cost of various preparations of antipsychotics (branded and generic) availabl...

  6. Benzodiazepines, benzodiazepine-like drugs, and typical antipsychotics impair manual dexterity in patients with schizophrenia.

    Science.gov (United States)

    Sasayama, Daimei; Hori, Hiroaki; Teraishi, Toshiya; Hattori, Kotaro; Ota, Miho; Matsuo, Junko; Kinoshita, Yukiko; Okazaki, Mitsutoshi; Arima, Kunimasa; Amano, Naoji; Higuchi, Teruhiko; Kunugi, Hiroshi

    2014-02-01

    Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Monitoring of Metabolic Adverse Effects Associated With Atypical Antipsychotics Use in an Outpatient Psychiatric Clinic.

    Science.gov (United States)

    Pereira, Luis; Budovich, Aliaksandr; Claudio-Saez, Maria

    2018-01-01

    Atypical antipsychotics are associated with metabolic complications that contribute to a higher risk of cardiovascular disease. Current evidence reveal suboptimal adherence to the complex and variable official recommendations on metabolic monitoring in the corresponding patient population. A study evaluating metabolic monitoring at guideline-recommended intervals may help identify areas for intervention. Describe the frequency of monitoring metabolic adverse effects in patients receiving atypical antipsychotics in an outpatient psychiatric clinic with respect to the specific guideline-recommended intervals. A retrospective chart review was conducted in the outpatient psychiatric clinic. The primary outcome measure was the percentage of patients monitored for metabolic parameters at the current guideline-recommended intervals. The secondary end points were the percentage of patients with documented primary care physician, untreated metabolic comorbidities, and treated metabolic comorbidities by disease state. The most assessed parameters were family history (98%), blood pressure (81%), and body mass index/body weight (83%) at the baseline interval. The least assessed parameters were lipids (14%) at the 12-week interval and waist circumference (0%) at any interval. Interventions are needed to encourage higher compliance with current recommendations. The complexity of the recommendations is the most likely reason for the suboptimal compliance.

  8. Dislipidemias e antipsicóticos atípicos Dyslipidemias and atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Edilberto Amorim de Cerqueira Filho

    2006-01-01

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

  9. Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; Herings, RMC; Roos, RAC; Jansen, PAF; Leufkens, HGM

    Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous

  10. Antipsychotic-induced extrapyramidal syndromes : Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, I; de Boer, A|info:eu-repo/dai/nl/075097346; Herings, R M; Roos, R A; Jansen, P A; Leufkens, H G|info:eu-repo/dai/nl/075255049

    AIM: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous

  11. Atypical Antipsychotics in the Treatment of Depressive and Psychotic Symptoms in Patients with Chronic Schizophrenia: A Naturalistic Study

    Directory of Open Access Journals (Sweden)

    Marco Innamorati

    2013-01-01

    Full Text Available Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients’ awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women treated with clozapine and 23 patients (16 men and 7 women treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS, depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS, and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD. Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds.

  12. Cost-effectiveness of adjunctive therapy with atypical antipsychotics for acute treatment of major depressive disorder.

    Science.gov (United States)

    Taneja, Charu; Papakostas, George I; Jing, Yonghua; Baker, Ross A; Forbes, Robert A; Oster, Gerry

    2012-05-01

    While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per

  13. Antipsychotic Drug Side Effects for Persons with Intellectual Disability

    Science.gov (United States)

    Matson, Johnny L.; Mahan, Sara

    2010-01-01

    Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…

  14. 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

  15. Chlorpromazine equivalents versus defined daily doses : How to compare antipsychotic drug doses?

    NARCIS (Netherlands)

    Rijcken, CAW; Monster, TBM; Brouwers, JRBJ; de Jong-van den Berg, LTW

    2003-01-01

    Classic chlorpromazine (CPZ) equivalents can be used to chart relative antipsychotic potencies of antipsychotic drugs. Values of CPZ equivalents per drug are ambiguous in literature. In drug use evaluation studies, antipsychotic doses are frequently compared by use of the defined daily dose (DDD).

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Pinaki Chakravarty

    2016-01-01

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

  18. 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.

  19. Antipsychotic drug use and risk of pneumonia in elderly people

    NARCIS (Netherlands)

    Knol, Wilma; Van Marum, Rob J.; Jansen, Paul A. F.; Souverein, Patrick C.; Schobben, Alfred F. A. M.; Egberts, Antoine C. G.

    OBJECTIVES: To investigate the association between antipsychotic drug use and risk of pneumonia in elderly people. DESIGN: A nested case-control analysis. SETTING: Data were used from the PHARMO database, which collates information from community pharmacies and hospital discharge records.

  20. Effect of augmented atypical antipsychotics on weight change in patients with major depressive disorder in a naturalistic setting.

    Science.gov (United States)

    Seo, Ho-Jun; Jung, Young-Eun; Woo, Young Sup; Jun, Tae-Youn; Chae, Jeong-Ho; Bahk, Won-Myong

    2009-03-01

    The extent of weight changes in depressed patients who use atypical antipsychotics (AAP) as augmentation could not be easily predicted due to weight related symptoms of depression and the interaction with antidepressants which have weight reducing effects. Patients were treated with either antidepressants augmented with AAP for more than 2 weeks (AAP group, n = 100) or only with antidepressants (non-AAP group, n = 172) during the admission between 2002 and 2006, and the differences in weight were analyzed. Mean weight gains of AAP group were significantly higher than those of non-AAP group (2.98 +/- 1.87 kg vs. 1.70 +/- 1.85 kg, p = 0.001). When stratified by antidepressants, the significant difference between the two groups was shown among the subjects who had taken serotonin reuptake inhibitors (SSRIs), but not mirtazapine and venlafaxine (3.42 +/- 2.01 kg vs. 1.48 +/- 1.79 kg, p depression could severely aggravate preexisting weight-related problems of antidepressants use and the possibility that the combined use with specific antidepressants could have a unique effect on weight by drug-drug interactions.

  1. A meta-analysis of cognitive change with haloperidol in clinical trials of atypical antipsychotics: dose effects and comparison to practice effects.

    Science.gov (United States)

    Woodward, Neil D; Purdon, Scot E; Meltzer, Herbert Y; Zald, David H

    2007-01-01

    Prospective, double-blind, randomized trials comparing atypical antipsychotic drugs (APDs) to typical APDs, such as haloperidol, indicate that atypical APDs provide a modest benefit to cognitive function in schizophrenia. However, the validity of this inference has been contested by suggestions that the cognitive improvements observed with atypical APDs reflect practice effects associated with repeated testing on the same neuropsychological instruments, or an avoidance of a deleterious effect of haloperidol on cognitive function that might be dose related. These alternate hypotheses were assessed by meta-analyses that 1) examined the relationship between cognitive change and dose of haloperidol within the control arms of prospective atypical vs. typical APD clinical trials; and 2) compared the magnitude of change observed within the haloperidol arms of these studies to estimated practice effects for several commonly used neuropsychological measures. The results indicate that overall cognitive performance improves while on haloperidol. Studies that used a low dose of haloperidol (10 mg), although doses greater than 24 mg appear to have deleterious effects. For two of the six neuropsychological tests examined (digit symbol substitution and verbal fluency) the magnitude of change observed was significantly less than practice effects. The results indicate that although haloperidol may cause deleterious effects at very high doses, or in specific cognitive domains, these effects are not likely to explain the broader range of cognitive improvements observed with atypical APDs.

  2. Cost-effectiveness of early responders versus early nonresponders to atypical antipsychotic therapy

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    Peng X

    2011-04-01

    Full Text Available Xiaomei Peng1, Haya Ascher-Svanum1, Douglas E Faries1, Virginia L Stauffer1, Sara Kollack-Walker1, Bruce J Kinon1, John M Kane21Eli Lilly and Company, Indianapolis, Indiana; 2Zucker Hillside Hospital, Department of Psychiatry, Glen Oaks, New York, USABackground: To compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine.Methods: This post hoc analysis used data from a randomized, double-blind, 12-week schizophrenia study (Study Code: HGMN, n = 628. Participants were initially assigned to risperidone therapy. Early response was defined as a ≥ 20% improvement on the Positive and Negative Syndrome Scale (PANSS total score from baseline to two weeks. Early responders continued on risperidone, whereas early nonresponders were randomized in a double-blind manner to continue on risperidone or switch to olanzapine for 10 additional weeks. Early responders and early nonresponders maintained on risperidone were compared for health-state utilities (benefits and total cost over the 12-week study; early nonresponders maintained on risperidone or switched to olanzapine were compared from randomization (10-week period. Utilities were derived from the PANSS and adverse events. Mixed models were used to assess group differences in utilities. Treatment costs were calculated based on health states. Incremental cost-effectiveness ratios were then utilized to compare treatment groups.Results: Early responders to risperidone had significantly greater total utility and lower total treatment costs than early nonresponders to risperidone. Compared with early nonresponders who continued on risperidone, those who were switched to olanzapine had significantly higher total utility scores at endpoint and numerically lower total treatment costs, reflecting significantly lower

  3. 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.

  4. The impact of atypical antipsychotic use on obstructive sleep apnea: A pilot study and literature review

    Science.gov (United States)

    Shirani, Afshin; Paradiso, Sergio; Dyken, Mark Eric

    2013-01-01

    Background Limited evidence links atypical antipsychotics (AAs) use to sleep related respiratory dysfunction and greater severity of obstructive sleep apnea (OSA). The present paper reviews the published evidence and examines the impact of AA use on the presence and severity of OSA among subjects with clinically suspected OSA after adjusting for several confounds. Methods Archives of the University of Iowa Sleep Laboratory from 2005 to 2009 were searched for patients using AAs at the time of diagnostic polysomnogram (PSG). PSG data of the 84 AA users with heterogeneous psychiatric disorders (of these 20 diagnosed only with depression) were subsequently compared to PSG data of two randomly selected, non-AA user groups from the same patient pool: (i) 200 subjects with a depressive disorder as the only psychiatric diagnosis, and (ii) 331 mentally healthy controls. PSG data were analyzed adjusting for known demographic, medical, and psychiatric risk factors for OSA. Results Prevalence and severity of OSA did not differ significantly across three groups. Sex, age, body mass index (BMI), and neck circumference (NC) independently predicted OSA. Odds ratio for OSA in the subset of AA users carrying the diagnosis of depression (n = 20) compared with subjects without mental illness was 4.53 (p depression or those with multiple psychiatric diagnoses including depression did not show a statistically significantly elevated OSA risk. Conclusions AA use in subjects with depression appears to increase the risk of OSA after controlling for known predisposing factors. PMID:21645873

  5. Prevalence and correlates of atypical patterns of drug use progression

    African Journals Online (AJOL)

    None of the anxiety or mood disorders were associated with atypical patterns of use. Atypical patterns of drug use were not associated with increased risk for a lifetime substance use disorder. Conclusion: Atypical patterns of drug use initiation seem more prevalent in South Africa compared to other countries. The early use ...

  6. Preclinical models of antipsychotic drug action

    Science.gov (United States)

    Moreno, José L.; González-Maeso, Javier

    2016-01-01

    One of the main obstacles faced by translational neuroscience is the development of animal models of psychiatric disorders. Behavioural pharmacology studies indicate that psychedelic drugs, such as lysergic acid diethylamide (LSD) and dissociative drugs, such as phencyclidine (PCP), induce in healthy human volunteers psychotic and cognitive symptoms that resemble some of those observed in schizophrenia patients. Serotonin 5-HT2A and metabotropic glutamate 2 receptors have been involved in the mechanism of action of psychedelic and dissociative drugs. Here we review recent advances using LSD-like and PCP-like drugs in rodent models that implicate these receptors in the neurobiology of schizophrenia and its treatment. PMID:23745738

  7. Phencyclidine-induced disruption of oscillatory activity in prefrontal cortex: Effects of antipsychotic drugs and receptor ligands.

    Science.gov (United States)

    Lladó-Pelfort, L; Troyano-Rodriguez, E; van den Munkhof, H E; Cervera-Ferri, A; Jurado, N; Núñez-Calvet, M; Artigas, F; Celada, P

    2016-03-01

    The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP) markedly disrupts thalamocortical activity, increasing excitatory neuron discharge and reducing low frequency oscillations (LFO, <4Hz) that temporarily group neuronal discharge. These actions are mainly driven by PCP interaction with NMDA-R in GABAergic neurons of the thalamic reticular nucleus and likely underlie PCP psychotomimetic activity. Here we report that classical (haloperidol, chlorpromazine, perphenazine) and atypical (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripripazole) antipsychotic drugs--but not the antidepressant citalopram--countered PCP-evoked fall of LFO in the medial prefrontal cortex (mPFC) of anesthetized rats. PCP reduces LFO by breaking the physiological balance between excitatory and inhibitory transmission. Next, we examined the role of different neurotransmitter receptors to reverse PCP actions. D2-R and D1-R blockade may account for classical antipsychotic action since raclopride and SCH-23390 partially reversed PCP effects. Atypical antipsychotic reversal may additionally involve 5-HT1A-R activation (but not 5-HT2A-R blockade) since 8-OH-DPAT and BAYx3702 (but not M100907) fully countered PCP effects. Blockade of histamine H1-R (pyrilamine) and α1-adrenoceptors (prazosin) was without effect. However, the enhancement of GABAA-R-mediated neurotransmission (using muscimol, diazepam or valproate) and the reduction of excitatory neurotransmission (using the mGluR2/3 agonist LY379268 and the preferential kainite/AMPA antagonist CNQX--but not the preferential AMPA/kainate antagonist NBQX) partially or totally countered PCP effects. Overall, these results shed new light on the neurobiological mechanisms used by antipsychotic drugs to reverse NMDA-R antagonist actions and suggest that agents restoring the physiological excitatory/inhibitory balance altered by PCP may be new targets in antipsychotic drug development. Copyright © 2015 Elsevier B

  8. Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

    Science.gov (United States)

    Wang, Bo; Franklin, Jessica M; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S

    2016-01-01

    Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

  9. Dose Equivalents for Antipsychotic Drugs: The DDD Method.

    Science.gov (United States)

    Leucht, Stefan; Samara, Myrto; Heres, Stephan; Davis, John M

    2016-07-01

    Dose equivalents of antipsychotics are an important but difficult to define concept, because all methods have weaknesses and strongholds. We calculated dose equivalents based on defined daily doses (DDDs) presented by the World Health Organisation's Collaborative Center for Drug Statistics Methodology. Doses equivalent to 1mg olanzapine, 1mg risperidone, 1mg haloperidol, and 100mg chlorpromazine were presented and compared with the results of 3 other methods to define dose equivalence (the "minimum effective dose method," the "classical mean dose method," and an international consensus statement). We presented dose equivalents for 57 first-generation and second-generation antipsychotic drugs, available as oral, parenteral, or depot formulations. Overall, the identified equivalent doses were comparable with those of the other methods, but there were also outliers. The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure. The major limitations are that the information used to estimate DDDS is likely to differ between the drugs. Moreover, this information is not publicly available, so that it cannot be reviewed. The WHO stresses that DDDs are mainly a standardized measure of drug consumption, and their use as a measure of dose equivalence can therefore be misleading. We, therefore, recommend that if alternative, more "scientific" dose equivalence methods are available for a drug they should be preferred to DDDs. Moreover, our summary can be a useful resource for pharmacovigilance studies. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Antipsicóticos atípicos e comportamento suicida em pacientes esquizofrênicos ou esquizoafetivos Atypical antipsychotics and suicidal behavior in esquizophrenic or schizo-affective patients

    Directory of Open Access Journals (Sweden)

    Felipe Filardi da Rocha

    2010-01-01

    Full Text Available CONTEXTO: Os estudos a respeito da ação dos antipsicóticos atípicos no comportamento suicida são controversos e pouco explorados. OBJETIVOS: Análise discursiva da ação dos antipsicóticos atípicos no comportamento suicida de pacientes esquizofrênicos ou esquizoafetivos. MÉTODOS: Revisão de artigos nas bases de dados MEDLINE, LILACS e da Biblioteca Cochrane, entre o período de 1964 e 2009, usando as palavras-chave: "suicidal behavior" e/ou "suicide" e "atypical antipsychotics" e/ou "antipsychotics" e/ou "clozapine". RESULTADOS: As únicas evidências significativas positivas apontam para a clozapina, que apresenta uma relevância superior aos outros antipsicóticos de segunda geração na redução das taxas de autoextermínio. CONCLUSÕES: A clozapina é o único fármaco que pode alterar o comportamento suicida. Esse efeito não está associado à melhora clínica dos pacientes. Ela é a única droga aprovada pelo Food and Drug Administration (FDA para prevenir suicídio em pacientes esquizofrênicos, mas os critérios para esse fim são incertos.BACKGROUND: The literature concerning the net effect of atypical antipsychotic medication on suicidality is not consistent. OBJECTIVES: The empirical literature relating to the efficacy of pharmacological intervention with atypical antipsychotics in esquizophrenic or schizo-affective patients is comprehensively reviewed. METHODS: MEDLINE, LILACS and Cochrane Library were used to search for articles from 1964 to 2009 using these key-words: "suicidal behavior" e/ou "suicide" e "atypical antipsychotics" e/ou "antipsychotics" e/ou "clozapine". RESULTS: The strongest and perhaps unique evidence has been shown for clozapine, which seems to have a clinically relevant advantage over other second-generation antipsychotics for reducing suicidality temptation. DISCUSSION: Clozapine is the unique medication that modulates suicidal behavior. Its action is unknown but is not related do clinical

  11. A weight-independent association between atypical antipsychotic medications and obstructive sleep apnea.

    Science.gov (United States)

    Khazaie, Habibolah; Sharafkhaneh, Amir; Khazaie, Sepideh; Ghadami, Mohammad Rasoul

    2017-07-13

    With increasing use of atypical antipsychotic (AAP) agents, the concern has been raised about the association between AAP agents and medical complications. Obstructive sleep apnea (OSA) is a common breathing disorder that adversely affects health and quality of life. Because the major risk factors for OSA are weight gain and obesity by altering the upper airway anatomy, an association between AAP and development of OSA is predictable. However, we hypothesized that AAP may promote OSA not only by weight gain but also because of its potential effects on upper airway muscle function. In the present study, we evaluated the possible association between AAP use and the severity of OSA. A sample of patients using AAP for treatment of paradoxical insomnia was evaluated before and at least 8 weeks after AAP use. Patients were divided based on type of AAP use to olanzapine, risperidone, and quetiapine groups. Patients used olanzapine (5-10 mg), risperidone (2-4 mg), or quetiapine (100-200 mg) 2 h before bedtime. Before and after treatment, respiratory variables were recorded using polysomnography. BMI, neck circumference (NC), and waist circumference (WC) were measured before and after treatment period. There was no significant difference between pre- and post-treatment apnea index (0.2 ± 0.6 vs. 2.6 ± 4.3; p = 0.094) in olanzapine group. However, significant differences in hypopnea index (5.1 ± 5 vs. 30 ± 10.8; p weight gain as a main risk factor of OSA, our finding demonstrated a weight-independent association between AAP medications and worsening respiration during sleep.

  12. The potential role of atypical antipsychotics for the treatment of posttraumatic stress disorder.

    Science.gov (United States)

    Han, Changsu; Pae, Chi-Un; Wang, Sheng-Min; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Praksh S; Serretti, Alssandro

    2014-09-01

    Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95% confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P CAPS (SMD = -0.373, 95% CIs = -0.568, -0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Naudin, J; Dassa, D; Cermolacce, M

    2009-09-01

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

  14. Central Retinal Vein Occlusion in 2 Patients Using Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Koichiro Taki

    2017-07-01

    Full Text Available Purpose: To report our findings in 2 patients who developed a central retinal vein occlusion (CRVO and were chronic users of antipsychotic medications. Case Presentation: Case 1 was a 62-year-old woman who had a sudden reduction of vision in her right eye to 20/2,000. Her fundus showed signs of an impending CRVO with marked macular edema. She had been taking antipsychotic drugs (quetiapine fumarate and risperidone for about 2 years. She refused anti-VEGF therapy for her macular edema but selected systemic kallidinogenase. Two days later, the macular edema was significantly reduced but the number of cotton wool spots (CWS was increased. Ten days later, the macular edema was resolved and her BCVA improved to 20/60. The CWS gradually disappeared, and her BCVA improved to 20/20. Case 2 was a 43-year-old man who presented with vision reduction in his right eye of 1 week’s duration. His BCVA was 20/50 and his fundus showed signs of a CRVO-related macular edema with CWS in the peripapillary area. He had been taking sulpiride (DogmatylTM for depression for 1 year, and his blood test showed an increase in red blood cells and hematocrit. Anti-VEGF therapy was performed, and the macular edema was resolved with vision improving to 20/20. There has been no recurrence to date in both cases. Conclusions: These results indicate that a CRVO can be a complication of chronic use of antipsychotic medications. However, early treatment can lead to good outcomes. Clinicians should question patients who develop a sudden CRVO whether they are using antipsychotic medications.

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

    Science.gov (United States)

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

    2014-01-01

    INTRODUCTION 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. METHODS 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. RESULTS 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. CONCLUSION Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature. PMID:24452974

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

    Science.gov (United States)

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

    2005-01-01

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

  17. Prevalence of concomitant oral antipsychotic drug use among patients treated with long-acting, intramuscular, antipsychotic medications.

    Science.gov (United States)

    Aggarwal, Neil Krishan; Sernyak, Michael J; Rosenheck, Robert A

    2012-06-01

    Long-acting injectable (LAI) antipsychotic drugs are viewed as monotherapeutic alternatives to oral medications to promote medication adherence, but there have been no descriptive studies of concomitant use of oral and LAI medications. A list of all patients receiving services from the Connecticut Mental Health Center from July 1, 2009, to June 30, 2010, was obtained from center administrative records, and those carrying an initial intake diagnosis of schizophrenia or schizoaffective disorder were identified. All team leaders were approached, and all clinicians were asked to identify patients on their case load prescribed LAIs during the time interval above. Also, all internal and external pharmacy orders were reviewed. Concomitancy was defined as simultaneous oral and LAI antipsychotic use at any time from July 1, 2009, to June 30, 2010. Data were culled from the medical records using a form (available on request) that recorded current LAI antipsychotic, reasons for LAI use, length of time on LAI, monthly dosage, and all concomitant oral antipsychotics, antidepressants, and anxiolytic agents. Among 124 patients on LAI medications, 57 (46%) received concomitant oral and LAI antipsychotics: 27 (47%) were prescribed LAI haloperidol, 19 (33%) LAI fluphenazine, and 11 (19%) risperidone microspheres. Logistic regression showed greater use of oral antipsychotic for both Hispanic ethnicity (odds ratio, 3.8; 95% confidence interval, 1.3-10.8) and alcohol abuse/dependence (odds ratio, 6.5; 95% confidence interval, 1.3-31.9), with no significant differences on other variables. There were no significant differences between LAI agents in rates of use of concomitant oral antipsychotic, anticholinergic, sedative/hypnotic, or mood stabilizer. Patients were more likely to be prescribed concomitant oral preparations of their LAI agent than another oral antipsychotic. Higher dosing of LAI treatments was associated with a significantly greater likelihood of use of oral psychotropics

  18. Efficacy of Atypical Antipsychotics in the Management of Acute Agitation and Aggression in Hospitalized Patients with Schizophrenia or Bipolar Disorder: Results from a Systematic Review.

    Science.gov (United States)

    Yu, Xin; Correll, Christoph U; Xiang, Yu-Tao; Xu, Yifeng; Huang, Jizhong; Yang, Fude; Wang, Gang; Si, Tianmei; Kane, John M; Masand, Prakash

    2016-10-25

    Acute agitation and aggression are common symptoms in patients with bipolar disorder and schizophrenia. In this review, we discuss the prevalence, clinical assessment strategies, treatment options, and current Western and Chinese guidelines for the management of acute agitation and aggression in patients with bipolar disorder or schizophrenia. Among available approaches, we discuss in detail recent evidence supporting the use of intramuscular (IM) antipsychotics and some recently approved oral atypical antipsychotics for the management of acute aggression and agitation in hospitalized patients with bipolar disorder or schizophrenia presenting with acute agitation or aggression, highlighting some differences between individual antipsychotic agents.

  19. Antipsychotic-induced Hyperprolactinemia

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    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

  20. Intraoperative floppy-iris syndrome associated with use of antipsychotic drugs.

    Science.gov (United States)

    Matsuo, Masato; Sano, Ichiya; Ikeda, Yoshifumi; Fujihara, Etsuko; Tanito, Masaki

    2016-08-01

    We report 3 cases of intraoperative floppy-iris syndrome (IFIS) during cataract surgery in patients without a history of selective α1-blocker use but with a long-term history of antipsychotic drug use. We reviewed previously reported cases of antipsychotic drug-associated IFIS cases. Observational case series. In case 1, bilateral IFIS developed in a 39-year-old man with chronic angle-closure glaucoma. He had used several classes of antipsychotic drugs to treat schizophrenia, including the first-generation antipsychotic drugs haloperidol and chlorpromazine, the dopamine system stabilizer aripiprazole, the dopamine serotonin antagonists olanzapine and quetiapine, and the serotonin dopamine antagonists risperidone and blonanserin for 7 years. In case 2, a 63-year-old woman with schizophrenia had used aripiprazole, quetiapine, and risperidone for more than 10 years. In case 3, a 65-year-old woman with an organic mental disorder had used haloperidol for more than 10 years. At least 5 cases of antipsychotic drug-induced IFIS have been reported in the literature. Any class of antipsychotic drugs can cause IFIS. Although antipsychotic drug-induced IFIS can be mild, surgeons should be alert to the possibility of IFIS when they treat patients with current and past use of antipsychotic drugs. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Millán-González, Ricardo

    2012-03-01

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

  2. 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.

  3. Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management.

    Science.gov (United States)

    Fang, Fang; Sun, Hongwei; Wang, Zuowei; Ren, Ming; Calabrese, Joseph R; Gao, Keming

    2016-09-01

    Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to

  4. Risk of Mortality (Including Sudden Cardiac Death and Major Cardiovascular Events in Atypical and Typical Antipsychotic Users: A Study with the General Practice Research Database

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    Tarita Murray-Thomas

    2013-01-01

    Full Text Available Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD, all-cause mortality (excluding suicide, coronary heart disease (CHD, and ventricular arrhythmias (VA. Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical, 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87; cardiac mortality 1.72 (95% CI: 1.42–2.07; SCD primary definition 5.76 (95% CI: 2.90–11.45; SCD secondary definition 2.15 (95% CI: 1.64–2.81; CHD 1.16 (95% CI: 0.94–1.44; and VA 1.16 (95% CI: 1.02–1.31. aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85; cardiac mortality 0.89 (95% CI: 0.82–0.97; and SCD secondary definition 0.76 (95% CI: 0.55–1.04. Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

  5. Risk of mortality (including sudden cardiac death) and major cardiovascular events in atypical and typical antipsychotic users: a study with the general practice research database.

    Science.gov (United States)

    Murray-Thomas, Tarita; Jones, Meghan E; Patel, Deven; Brunner, Elizabeth; Shatapathy, Chetan C; Motsko, Stephen; Van Staa, Tjeerd P

    2013-01-01

    Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64-1.87); cardiac mortality 1.72 (95% CI: 1.42-2.07); SCD primary definition 5.76 (95% CI: 2.90-11.45); SCD secondary definition 2.15 (95% CI: 1.64-2.81); CHD 1.16 (95% CI: 0.94-1.44); and VA 1.16 (95% CI: 1.02-1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80-0.85); cardiac mortality 0.89 (95% CI: 0.82-0.97); and SCD secondary definition 0.76 (95% CI: 0.55-1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

  6. 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

    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...

  7. Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia

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    Iwamoto Yohko

    2012-11-01

    Full Text Available Abstract Background Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS activity remain unclear. The purpose of this study was to investigate the dose-dependent effect of antipsychotic drugs and other clinical factors on ANS activity in an adequate sample size of patients with schizophrenia. Methods A total of 211 Japanese patients with schizophrenia and 44 healthy subjects participated in this study. ANS activity was assessed by means of heart rate variability (HRV power spectral analysis. Antipsychotic drug treatment and various clinical factors were investigated for each participant. The patient group was categorized into three subgroups according to daily dose of antipsychotic drug, and HRV was compared between groups. Results The results showed significantly decreased low-frequency and high-frequency components of HRV in the patient group compared to the control group. The high-dose group showed a significantly lower HRV than the medium-dose group and an even lower HRV than the low-dose group. In addition, a significant association between HRV and antipsychotic drug dose was identified by multiple regression analysis. HRV was not associated with age, sex, body mass index, duration of illness, or daily dose of other psychotropic drugs. Conclusion These results suggest that antipsychotic drugs exert a significant dose-dependent effect on the extent of decline in ANS activity, and that optimal antipsychotic medication is required to avoid possible cardiovascular adverse events in patients with schizophrenia.

  8. Impact of regulatory measures on antipsychotics drug consumption in Castilla y León, Spain.

    Science.gov (United States)

    Martín Arias, L H; Treceño Lobato, C; Pérez García, S; García Ortega, P; Sáinz Gil, M; Sanz Fadrique, R; Carvajal García-Pando, A

    2016-12-01

    Antipsychotics are currently used to treat different diseases; even some off-labelled conditions are treated with this medication. Consumption and cost of antipsychotic drugs sharply increased in Spain after second-generation drugs were marketed; several regulatory measures were adopted to curb this trend. The aim of this study was to examine the impact of these measures upon the use and cost of antipsychotics. Study of drug use (SDU) from 1995 to 2012. Consumption and cost data were obtained from the CONCYLIA database; this database contains the retail community pharmacies sales of medicinal products reimbursed by the National Health System in Castilla y León (Spain). Data are presented as defined daily doses per 1000 inhabitants per day (DID) and day treatment cost (DTC). First-generation antipsychotics prescriptions gradually decreased from 3.0 to 1.8 DID; meanwhile, prescriptions for second-generation antipsychotics considerably increased from 0.3 to 9.9 DID. The use of risperidone dropped after the marketing of its structural derivative paliperidone with a similar efficacy but with a substantially higher cost per day. In 2011 and thereafter, patients in Spain began to pay a part of the medications cost, but this did not decrease antipsychotics consumption. Global cost of antipsychotics only began to fall after measures were adopted to lower the price of medicines because of the economic collapse in Spain after May 2010. Several health policy measures have tried to reduce antipsychotics consumption in Spain, special ways of dispensing, marketing of generic drugs and special economic measures for patients. These measures eventually failed to avoid the increase in antipsychotics use. The cost only dropped when lowering prescription drug prices took place. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  9. Comparison of health-related quality of life among patients using atypical antipsychotics for treatment of depression: results from the National Health and Wellness Survey

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    Kalsekar Iftekhar

    2012-07-01

    Full Text Available Abstract Background Use of atypical antipsychotics (AA in combination with an antidepressant is recommended as an augmentation strategy for patients with depression. However, there is a paucity of data comparing aripiprazole and other AAs in terms of patient reported outcomes. Therefore, the objective of this study was to examine the levels of HRQoL and health utility scores in patients with depression using aripiprazole compared with patients using olanzapine, quetiapine, risperidone and ziprasidone. Methods Data were obtained from the 2009, 2010, and 2011 National Health and Wellness Survey (NHWS, a cross-sectional, internet-based survey that is representative of the adult US population. Only those patients who reported being diagnosed with depression and taking an antidepressant and an atypical antipsychotic for depression were included. Patients taking an atypical antipsychotic for less than 2 months or who reported being diagnosed with bipolar disorder or schizophrenia were excluded. Patients taking aripiprazole were compared with patients taking other atypical antipsychotics. Health-related quality of life (HRQoL and health utilities were assessed using the Short Form 12-item (SF-12 health survey. Differences between groups were analyzed using General Linear Models (GLM controlling for demographic and health characteristics. Results Overall sample size was 426 with 59.9% taking aripiprazole (n = 255 and 40.1% (n = 171 taking another atypical antipsychotic (olanzapine (n = 19, quetiapine (n = 127, risperidone (n = 14 or ziprasidone (n = 11. Of the SF-12 domains, mean mental component summary (MCS score (p = .018, bodily pain (p = .047, general health (p = .009 and emotional role limitations (p = .009 were found to be significantly higher in aripiprazole users indicating better HRQoL compared to other atypical antipsychotics. After controlling for demographic and health characteristics, patients

  10. Comparison of health-related quality of life among patients using atypical antipsychotics for treatment of depression: results from the National Health and Wellness Survey.

    Science.gov (United States)

    Kalsekar, Iftekhar; Wagner, Jan-Samuel; DiBonaventura, Marco; Bates, Jay; Forbes, Robert; Hebden, Tony

    2012-07-17

    Use of atypical antipsychotics (AA) in combination with an antidepressant is recommended as an augmentation strategy for patients with depression. However, there is a paucity of data comparing aripiprazole and other AAs in terms of patient reported outcomes. Therefore, the objective of this study was to examine the levels of HRQoL and health utility scores in patients with depression using aripiprazole compared with patients using olanzapine, quetiapine, risperidone and ziprasidone. Data were obtained from the 2009, 2010, and 2011 National Health and Wellness Survey (NHWS), a cross-sectional, internet-based survey that is representative of the adult US population. Only those patients who reported being diagnosed with depression and taking an antidepressant and an atypical antipsychotic for depression were included. Patients taking an atypical antipsychotic for less than 2 months or who reported being diagnosed with bipolar disorder or schizophrenia were excluded. Patients taking aripiprazole were compared with patients taking other atypical antipsychotics. Health-related quality of life (HRQoL) and health utilities were assessed using the Short Form 12-item (SF-12) health survey. Differences between groups were analyzed using General Linear Models (GLM) controlling for demographic and health characteristics. Overall sample size was 426 with 59.9% taking aripiprazole (n=255) and 40.1% (n=171) taking another atypical antipsychotic (olanzapine (n=19), quetiapine (n=127), risperidone (n=14) or ziprasidone (n=11)). Of the SF-12 domains, mean mental component summary (MCS) score (p=.018), bodily pain (p=.047), general health (p=.009) and emotional role limitations (p=.009) were found to be significantly higher in aripiprazole users indicating better HRQoL compared to other atypical antipsychotics. After controlling for demographic and health characteristics, patients taking aripiprazole reported significantly higher mean mental SF-12 component summary (34.10 vs. 31

  11. Antipsychotic drug treatment in the prodromal phase of schizophrenia.

    Science.gov (United States)

    Cannon, Tyrone D; Huttunen, Matti O; Dahlström, Minna; Larmo, Ilkka; Räsänen, Pirkko; Juriloo, Alo

    2002-07-01

    The safety and tolerability of short-term treatment with a low dose of risperidone was evaluated in adolescents with prodromal symptoms and a family history of schizophrenia. Four prodromal high-risk adolescents and six first-episode patients with schizophrenia were treated with average doses of 1.0 and 1.8 mg/day of risperidone, respectively, in an 8- to 12-week open-label trial. No significant treatment-related adverse events were noted. Severity of thought and behavior disturbance ratings declined by about 30%; performance on a test of verbal learning improved by about 100% during treatment in both prodromal and first-episode patients, changes that achieved statistical significance despite the small group sizes. These findings are preliminary and should not be used to guide health care decisions at this time. Randomized controlled trials are needed to determine whether antipsychotic drug treatment of prodromal patients can delay or prevent onset or attenuate the clinical course of schizophrenia.

  12. 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.

  13. Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

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    Jiezhong Chen

    2017-11-01

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

  14. Do antipsychotic drugs increase seizure frequency in epilepsy patients?

    Science.gov (United States)

    Okazaki, Mitsutoshi; Adachi, Naoto; Akanuma, Nozomi; Hara, Koichiro; Ito, Masumi; Kato, Masaaki; Onuma, Teiichi

    2014-11-01

    To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  15. The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito

    2016-05-15

    Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

    OpenAIRE

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun; Bahk, Won-Myong

    2016-01-01

    Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was pri...

  17. Comparison of health-related quality of life among patients using atypical antipsychotics for treatment of depression: results from the National Health and Wellness Survey

    OpenAIRE

    Kalsekar, Iftekhar; Wagner, Jan-Samuel; DiBonaventura, Marco; Bates, Jay; Forbes, Robert; Hebden, Tony

    2012-01-01

    Abstract Background Use of atypical antipsychotics (AA) in combination with an antidepressant is recommended as an augmentation strategy for patients with depression. However, there is a paucity of data comparing aripiprazole and other AAs in terms of patient reported outcomes. Therefore, the objective of this study was to examine the levels of HRQoL and health utility scores in patients with depression using aripiprazole compared with patients using olanzapine, quetiapine, risperidone and zi...

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

    Directory of Open Access Journals (Sweden)

    Ping Shao

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

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

    Directory of Open Access Journals (Sweden)

    Pikalov Andrei

    2011-01-01

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

  20. Development and validation of a stability-indicating gas chromatographic method for quality control of residual solvents in blonanserin: a novel atypical antipsychotic agent.

    Science.gov (United States)

    Peng, Ming; Liu, Jin; Lu, Dan; Yang, Yong-Jian

    2012-09-01

    Blonanserin is a novel atypical antipsychotic agent for the treatment of schizophrenia. Ethyl alcohol, isopropyl alcohol and toluene are utilized in the synthesis route of this bulk drug. A new validated gas chromatographic (GC) method for the simultaneous determination of residual solvents in blonanserin is described in this paper. Blonanserin was dissolved in N, N-dimethylformamide to make a sample solution that was directly injected into a DB-624 column. A postrun oven temperature at 240°C for approximately 2 h after the analysis cycle was performed to wash out blonanserin residue in the GC column. Quantitation was performed by external standard analyses and the validation was carried out according to International Conference on Harmonization validation guidelines Q2A and Q2B. The method was shown to be specific (no interference in the blank solution), linear (correlation coefficients ≥0.99998, n = 10), accurate (average recoveries between 94.1 and 101.7%), precise (intra-day and inter-day precision ≤2.6%), sensitive (limit of detection ≤0.2 ng, and limit of quantitation ≤0.7 ng), robust (small variations of carrier gas flow, initial oven temperature, temperature ramping rate, injector and detector temperatures did not significantly affect the system suitability test parameters and peak areas) and stable (reference standard and sample solutions were stable over 48 h). This extensively validated method is ready to be used for the quality control of blonanserin.

  1. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans.

    Science.gov (United States)

    Donohoe, Dallas R; Weeks, Kathrine; Aamodt, Eric J; Dwyer, Donard S

    2008-01-01

    Antipsychotic drugs are increasingly being prescribed for children and adolescents, and are used in pregnant women without a clear demonstration of safety in these populations. Global effects of these drugs on neurodevelopment (e.g., decreased brain size) have been reported in rats, but detailed knowledge about neuronal effects and mechanisms of action are lacking. Here we report on the evaluation of a comprehensive panel of antipsychotic drugs in a model organism (Caenorhabditis elegans) that is widely used to study neuronal development. Specifically, we examined the effects of the drugs on neuronal migration and axonal outgrowth in mechanosensory neurons visualized with green fluorescent protein expressed from the mec-3 promoter. Clozapine, fluphenazine, and haloperidol produced deficits in the development and migration of ALM neurons and axonal outgrowth in PLM neurons. The defects included failure of neuroblasts to migrate to the proper location, and excessive growth of axons past their normal termination point, together with abnormal morphological features of the processes. Although the antipsychotic drugs are potent antagonists of dopamine and serotonin receptors, the neurodevelopmental deficits were not rescued by co-incubation with serotonin or the dopaminergic agonist, quinpirole. Other antipsychotic drugs, risperidone, aripiprazole, quetiapine, trifluoperazine and olanzapine, also produced modest, but detectable, effects on neuronal development. This is the first report that antipsychotic drugs interfere with neuronal migration and axonal outgrowth in a developing nervous system.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  3. Antipsychotic drugs: From receptor-binding profiles to metabolic side effects.

    Science.gov (United States)

    Siafis, Spyridon; Tzachanis, Dimitrios; Samara, Myrto; Papazisis, Georgios

    2017-06-30

    Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated. Antipsychotic drugs seem to interfere with feeding behaviors and energy balance processes that control metabolic regulation. Reward and energy balance centers in central nervous system constitute the central level of metabolic regulation. The peripheral level consists of skeletal muscles, the liver, the pancreas, the adipose tissue and neuroendocrine connections. Neurotransmitter receptors have crucial roles in metabolic regulation and they are also targets of antipsychotic drugs. Interaction of antipsychotics with neurotransmitters could have both protective and harmful effects on metabolism. Emerging evidence suggests that antipsychotics have different liabilities to induce obesity, diabetes and dyslipidemia. However, this diversity cannot be explained merely by drugs' pharmacodynamic profiles, highlighting the need for further research. Herein, we review the impact of neurotransmitters on metabolic regulation, providing insights into antipsychotic-induced metabolic side effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Remission, response, and relapse rates in patients with acute schizophrenia treated with olanzapine monotherapy or other atypical antipsychotic monotherapy: 12-month prospective observational study.

    Science.gov (United States)

    Takahashi, Michihiro; Nakahara, Naohiro; Fujikoshi, Shinji; Iyo, Masaomi

    2015-01-01

    To compare the rates of antipsychotic response, remission, and relapse in patients with schizophrenia treated with olanzapine or other antipsychotics in usual clinical care in Japan. This analysis of a 12-month, prospective, noninterventional study examined outcomes for 1,089 inpatients and outpatients with schizophrenia who initiated antipsychotic monotherapy. All treatment decisions, including medication choice, were left to the discretion of the treating physician. The rates of treatment response, relapse, and 6-month sustained remission were compared between olanzapine monotherapy (OLZ) and other anti-psychotic monotherapy (OAN), and between OLZ and other atypical antipsychotic monotherapy (OAT). Visit-wise comparisons of treatment response and remission were examined using repeated-measures logistic regressions. Propensity scores were used to control for potential baseline differences between groups. Response rates were higher for OLZ patients and relapse rates were consistently lower for OLZ patients, however the differences were not statistically significant. Rates of 6-month sustained remission were significantly higher for OLZ than OAN patients (P=0.032) and for OLZ than OAT patients (P=0.041). An exploratory analysis of OLZ and OAN comparison found outpatients treated with OLZ or OAN had similar sustained remission rates (OLZ: 22.2%, OAN: 22.8%), while inpatients treated with OLZ had significantly higher sustained remission rates than inpatients treated with OAN (OLZ: 17.1%, OAN: 6.6%, odds ratio [95% confidence interval] =3.54 [2.00-6.25]). In usual care in Japan, treating the acute symptoms of schizophrenia with olanzapine was not found to be significantly different for response and relapse rates; however, treatment with olanzapine was found to have significantly greater sustained remission rates than treatment with other antipsychotics. In the inpatient setting, where patients tend to be more severe and difficult to manage, olanzapine treatment may

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

    Directory of Open Access Journals (Sweden)

    Kensuke Sakuma

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

  6. Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: analysis of the CATIE phase 2E data.

    Science.gov (United States)

    Nakajima, Shinichiro; Takeuchi, Hiroyoshi; Fervaha, Gagan; Plitman, Eric; Chung, Jun Ku; Caravaggio, Fernando; Iwata, Yusuke; Mihashi, Yukiko; Gerretsen, Philip; Remington, Gary; Mulsant, Benoit; Graff-Guerrero, Ariel

    2015-02-01

    The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models. No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone. The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Decrease of antiparkinsonian drugs before start of an antipsychotic in patients on levodopa treatment?

    NARCIS (Netherlands)

    van de Vijver, David A M C; Roos, Raymund A C; Jansen, Paul A F; Porsius, Arijan J; de Boer, Anthonius

    2004-01-01

    INTRODUCTION: Antiparkinsonian drugs can induce behavioural disturbances, which should be treated by first reducing antiparkinsonian drugs and/or starting a benzodiazepine. If this approach fails, then antipsychotics can be considered. The aim of this study was to determine how often

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

    Directory of Open Access Journals (Sweden)

    Cakir S

    2016-09-01

    Full Text Available Sibel Cakir,1 Zeynep Senkal2 1Department of Psychiatry, Mood Disorders, Geriatric Psychiatry Unit, Istanbul Medical School, Istanbul University, 2Department of Psychiatry, Marmara University, Istanbul, Turkey Background: Second-generation antipsychotics (SGAs have been used in the augmentation of treatment-resistant depression. However, little is known about their effectiveness, tolerability, and adverse events in the treatment of late-life depression, which were the aim of this study.Methods: The retrospective data of patients aged >65 years who had a major depressive episode with inadequate response to antidepressant treatment and had adjuvant SGA treatment were analyzed. The outcome measures were the number of the patients who continued to use SGAs in the fourth and twelfth weeks, adverse events, and changes in symptoms of depression. Results: Thirty-five patients were screened: 21 (60% had quetiapine, twelve (34.28% had aripiprazole, and two (5.71% had olanzapine adjuvant treatment. The mean age was 72.17±5.02 years, and 65.7% of the patients were women. The mean daily dose was 85.71±47.80 mg for quetiapine, 3.33±1.23 mg for aripiprazole, and 3.75±1.76 mg for olanzapine. The Geriatric Depression Scale scores of all patients were significantly decreased in the fourth week and were significant in the aripiprazole group (P=0.02. Of the 35 patients, 23 (65.7% patients discontinued the study within 12 weeks. The frequency of adverse events was similar in all SGAs, and the most common were sedation, dizziness, constipation, and orthostatic hypotension with quetiapine, and akathisia and headache because of aripiprazole. Conclusion: This study indicates that dropout ratio of patients with SGAs is high, and a subgroup of patients with late-life depression may benefit from SGAs. Effectiveness is significant in aripiprazole, and adverse events of SGAs were not serious but common in elderly patients. Keywords: treatment resistance, aripiprazole

  9. Number Needed to Treat to Harm for Discontinuation Due to Adverse Events in the Treatment of Bipolar Depression, Major Depressive Disorder, and Generalized Anxiety Disorder With Atypical Antipsychotics

    Science.gov (United States)

    Gao, Keming; Kemp, David E.; Fein, Elizabeth; Wang, Zuowei; Fang, Yiru; Ganocy, Stephen J.; Calabrese, Joseph R.

    2012-01-01

    Objective To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). Data Sources English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder, and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. Study Selection Studies with a cumulative sample of ≥ 100 patients were included. Data Extraction The NNTHs for discontinuation due to adverse events, somnolence, sedation, ≥ 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. Data Synthesis Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. Conclusions At the same dose

  10. Number needed to treat to harm for discontinuation due to adverse events in the treatment of bipolar depression, major depressive disorder, and generalized anxiety disorder with atypical antipsychotics.

    Science.gov (United States)

    Gao, Keming; Kemp, David E; Fein, Elizabeth; Wang, Zuowei; Fang, Yiru; Ganocy, Stephen J; Calabrese, Joseph R

    2011-08-01

    To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder; and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. Studies with a cumulative sample of ≥ 100 patients were included. The NNTHs for discontinuation due to adverse events, somnolence, sedation, ≥ 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. At the same dose of quetiapine-XR, patients with GAD appeared to have a lower tolerability than

  11. 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...

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. The atypical antipsychotics clozapine and olanzapine promote down-regulation and display functional selectivity at human 5-HT7 receptors

    Science.gov (United States)

    Andressen, K W; Manfra, O; Brevik, C H; Ulsund, A H; Vanhoenacker, P; Levy, F O; Krobert, K A

    2015-01-01

    Background and Purpose Classically, ligands of GPCRs have been classified primarily upon their affinity and efficacy to activate a signal transduction pathway. Recent reports indicate that the efficacy of a particular ligand can vary depending on the receptor-mediated response measured (e.g. activating G proteins, other downstream responses, internalization). Previously, we reported that inverse agonists induce both homo- and heterologous desensitization, similar to agonist stimulation, at the Gs-coupled 5-HT7 receptor. The primary objective of this study was to determine whether different inverse agonists at the 5-HT7 receptor also induce internalization and/or degradation of 5-HT7 receptors. Experimental Approach HEK293 cells expressing 5-HT7(a, b or d) receptors were pre-incubated with 5-HT, clozapine, olanzapine, mesulergine or SB269970 and their effects upon receptor density, AC activity, internalization, recruitment of β-arrestins and lysosomal trafficking were measured. Key Results The agonist 5-HT and three out of four inverse agonists tested increased internalization independently of β-arrestin recruitment. Among these, only the atypical antipsychotics clozapine and olanzapine promoted lysosomal sorting and reduced 5-HT7 receptor density (∼60% reduction within 24 h). Inhibition of lysosomal degradation with chloroquine blocked the clozapine- and olanzapine-induced down-regulation of 5-HT7 receptors. Incubation with SB269970 decreased both 5-HT7(b) constitutive internalization and receptor density but increased 5-HT7(d) receptor density, indicating differential ligand regulation among the 5-HT7 splice variants. Conclusions and Implications Taken together, we found that various ligands differentially activate regulatory processes governing receptor internalization and degradation in addition to signal transduction. Thus, these data extend our understanding of functional selectivity at the 5-HT7 receptor. PMID:25884989

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

    DEFF Research Database (Denmark)

    Nielsen, René; 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...... mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P ... 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...

  16. The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes

    Science.gov (United States)

    Suessbrich, H; Schönherr, R; Heinemann, S H; Attali, B; Lang, F; Busch, A E

    1997-01-01

    The antipsychotic drug haloperidol can induce a marked QT prolongation and polymorphic ventricular arrhythmias. In this study, we expressed several cloned cardiac K+ channels, including the human ether-a-go-go related gene (HERG) channels, in Xenopus oocytes and tested them for their haloperidol sensitivity.Haloperidol had only little effects on the delayed rectifier channels Kv1.1, Kv1.2, Kv1.5 and IsK, the A-type channel Kv1.4 and the inward rectifier channel Kir2.1 (inhibition <6% at 3 μM haloperidol).In contrast, haloperidol blocked HERG channels potently with an IC50 value of approximately 1 μM. Reduced haloperidol, the primary metabolite of haloperidol, produced a block with an IC50 value of 2.6 μM.Haloperidol block was use- and voltage-dependent, suggesting that it binds preferentially to either open or inactivated HERG channels. As haloperidol increased the degree and rate of HERG inactivation, binding to inactivated HERG channels is suggested.The channel mutant HERG S631A has been shown to exhibit greatly reduced C-type inactivation which occurs only at potentials greater than 0 mV. Haloperidol block of HERG S631A at 0 mV was four fold weaker than for HERG wild-type channels. Haloperidol affinity for HERG S631A was increased four fold at +40 mV compared to 0 mV.In summary, the data suggest that HERG channel blockade is involved in the arrhythmogenic side effects of haloperidol. The mechanism of haloperidol block involves binding to inactivated HERG channels. PMID:9138706

  17. 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...

  18. Comparative Utility of Atypical Antipsychotics for the Treatment of Psychosis in Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.

    Science.gov (United States)

    Iketani, Ryo; Kawasaki, Yohei; Yamada, Hiroshi

    2017-01-01

    We performed a systematic review and Bayesian network meta-analysis to determine atypical antipsychotics that are effective and safe for the treatment of psychosis in Parkinson's disease (PD). We conducted a comprehensive literature search using PubMed/MEDLINE, Cochrane Library, and Japana Centra Revuo Medicina (Ichu-shi Web). We used randomized controlled trials evaluating the utility of atypical antipsychotics for the treatment of psychosis in PD using the Brief Psychiatric Rating Scale (BPRS) and the Unified PD rating Scale parts III (UPDRS-III) as the endpoints. Posterior distributions of mean differences between each treatment and placebo were estimated using Bayesian network meta-analysis. The distributions describing each treatment effect were expressed as means (95% credible intervals). Ten trials involving any two treatment arms using clozapine (64 subjects in four trials), olanzapine (99 subjects in three trials), quetiapine (79 subjects in five trials), risperidone (five subjects in one trial), or placebo (156 subjects in seven trials) were finally included in the present study. Pooled estimates of each posterior distribution based on the BPRS were as follows: clozapine, -2.0 (-6.7 to 2.7); olanzapine, 0.5 (-2.3 to 3.4); quetiapine, 0.3 (-3.9 to 4.5); and risperidone, -4.7 (-57.4 to 53.3). Based on the UPDRS-III, the pooled estimates were clozapine, 0.7 (-3.8 to 4.3); olanzapine, 2.8 (0.8 to 5.1); quetiapine, 3.3 (-0.7 to 5.8); and risperidone, 4.5 (-57.7 to 63.4). Although clozapine had an effective and relatively safe profile, all atypical antipsychotics included in the present study may be unsafe, as they may worsen motor function when compared to placebo.

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

    Science.gov (United States)

    Jensen, Ralph J

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Bodén R

    2013-03-01

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

  1. Antipsychotic medication-induced dysphoria: its meaning, association with typical vs. atypical medications and impact on adherence.

    Science.gov (United States)

    Wu, Hanjing Emily; Okusaga, Olaoluwa O

    2015-06-01

    Antipsychotic medication-induced dysphoria is a relatively under-recognized and understudied effect of antipsychotic medication. Although the term is encountered in clinical practice and in the literature, there is no consensus regarding its exact meaning. This article is a narrative review of the literature on antipsychotic medication and dysphoria based on a pubmed database search. We found that antipsychotic medication-induced dysphoria is a term used to describe a negative and unpleasant affective state which seems to be more often associated with high potency first-generation antipsychotics and could potentially lead to medication non-adherence. Though it is plausible to expect antipsychotic medication-induced dysphoria to be related to extrapyramidal symptoms, most especially akathisia, the nature of the association remains unspecified. Furthermore, there is some evidence that dopamine blockade maybe involved in the pathogenesis of antipsychotic medication-induced dysphoria. However, the limited methods of the currently available studies make it impossible to conclusively address the question of which class of antipsychotic (first- or second-generation) has a higher prevalence and severity of the syndrome.

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

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

    -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...

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

    NARCIS (Netherlands)

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

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

  4. Antipsychotic drugs activate the C. elegans akt pathway via the DAF-2 insulin/IGF-1 receptor.

    Science.gov (United States)

    Weeks, Kathrine R; Dwyer, Donard S; Aamodt, Eric J

    2010-06-16

    The molecular modes of action of antipsychotic drugs are poorly understood beyond their effects at the dopamine D2 receptor. Previous studies have placed Akt signaling downstream of D2 dopamine receptors, and recent data have suggested an association between psychotic illnesses and defective Akt signaling. To characterize the effect of antipsychotic drugs on the Akt pathway, we used the model organism C. elegans, a simple system where the Akt/forkhead box O transcription factor (FOXO) pathway has been well characterized. All major classes of antipsychotic drugs increased signaling through the insulin/Akt/FOXO pathway, whereas four other drugs that are known to affect the central nervous system did not. The antipsychotic drugs inhibited dauer formation, dauer recovery, and shortened lifespan, three biological processes affected by Akt signaling. Genetic analysis showed that AKT-1 and the insulin and insulin-like growth factor receptor, DAF-2, were required for the antipsychotic drugs to increase signaling. Serotonin synthesis was partially involved, whereas the mitogen activated protein kinase (MAPK), SEK-1 is a MAP kinase kinase (MAPKK), and calcineurin were not involved. This is the first example of a common but specific molecular effect produced by all presently known antipsychotic drugs in any biological system. Because untreated schizophrenics have been reported to have low levels of Akt signaling, increased Akt signaling might contribute to the therapeutic actions of antipsychotic drugs.

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

    Science.gov (United States)

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

    2014-09-01

    To assess the differences in antipsychotic drug prescription rates in residents with dementia in dementia special care units (SCUs) of Dutch nursing homes, considering the differences in patient characteristics. As part of the Waalbed-II study, the data on antipsychotic drug use in 290 patients were collected and the Global Deterioration Scale (GDS) stage, type of dementia and behaviour (Cohen-Mansfield Agitation Inventory (CMAI)) were measured in 14 SCUs in nine nursing homes. A multilevel logistic regression model was used to assess the difference in antipsychotic drug prescription rates between dementia SCUs adjusted for age, gender, GDS stage, type of dementia and CMAI factor scores. Two hundred and ninety residents met the inclusion criteria. Thirty-two per cent were prescribed an antipsychotic drug. Antipsychotic drugs were more often prescribed in patients with physically aggressive and non-aggressive behaviour and in patients with mixed dementia (vascular/Alzheimer's) than in patients with other types of dementia. Antipsychotic drug prescriptions significantly differed among the dementia SCUs. The odds of antipsychotic drug use for patients in the SCU with the highest prevalence of drug use were 2.76 (95% confidence interval (CI) 1.14-6.69) times as high as for the SCU with the lowest prevalence of drug use, taking the patient characteristics into account. Antipsychotic drug use in nursing home residents with dementia is not only predicted by the type of dementia and patient behaviour, but it is independently associated with the dementia SCU at which the patient resides. This result indicates that antipsychotic drugs are not only prescribed for their clinical indications (agitation/aggression) but are associated with environmental factors that may reflect a specific nursing home prescribing culture.

  6. Comparative effects of aripiprazole and selected antipsychotic drugs on lipid peroxidation in plasma.

    Science.gov (United States)

    Dietrich-Muszalska, Anna; Kolińska-Łukaszuk, Jolanta

    2017-12-27

    The aim of the present study was to evaluate and compare the effects of a new antipsychotic aripiprazole, unique due to its mechanism of action, with the effects of selected antipsychotic drugs such as quetiapine, olanzapine, clozapine, risperidone and ziprasidone (at the final concentrations corresponding to clinically effective doses used for the treatment of acute episodes of schizophrenia) on lipid peroxidation in human plasma measured by the level of TBARS (thiobarbituric acid reactive substances), which is a marker of oxidative stress. The level of TBARS were measured spectrophotometrically, according to the modification of the Rice-Evans method. Our results indicate that antipsychotics at doses recommended for the treatment of acute episodes of schizophrenia may induce distinct changes in the levels of lipid peroxidation products (TBARS) in plasma. Aripiprazole had no effect on the level of a lipid peroxidation marker in plasma, although used at lower doses it showed insignificant prooxidative properties similar to clozapine. Quetiapine had the strongest antioxidant properties, contrary to prooxidative action of risperidone, ziprasidone or haloperidol, and clozapine at lower doses. Olanzapine reduced the level of TBARS in plasma only at a lower dose. Antipsychotics at doses recommended for the treatment of acute episode in schizophrenia may induce the distinct changes in plasma lipid peroxidation. Aripiprazole did not induce significant changes in plasma lipid peroxidation. In further studies, the role of oxidative stress in schizophrenic patients together with their clinical symptomatology and use of antipsychotics should be taken into account. This article is protected by copyright. All rights reserved.

  7. Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy.

    Science.gov (United States)

    Swathy, Babu; Banerjee, Moinak

    2017-05-01

    The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects. We re-examine the context of epigenetics in disease pathogenesis and antipsychotic drug therapy in SCZ to understand how much of these observations act as real indicators of the disease or therapeutic response. We propose that epigenetic viewpoint in SCZ needs to be critically examined under the genetic, epigenetic and pharmacoepigenetic background.

  8. Mortality and Antipsychotic Drug Use in Elderly Patients With Parkinson Disease in Nursing Homes.

    Science.gov (United States)

    Thu Trang, Dao; Cool, Charlène; Laffon de Mazieres, Clarisse; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis; Rascol, Olivier; Rolland, Yves; Sommet, Agnès

    2017-09-01

    To evaluate mortality rate in elderly and very elderly (≥85 years) residents with Parkinson disease (PD) in nursing homes (NHs) with and without antipsychotic drugs. Cross-sectional study. All residents with PD from the 6275 NH residents participating in the Impact d'une démarche QUAlité sur l'évolution des pratiques et le déclin fonctionnel des Résidents en Etablissement d'hébergement pour personnes âgées dépendantes (IQUARE) study. A total of 175 NHs in Midi-Pyrénées region, South-Western France. Patients with PD taking antipsychotic drugs. All-cause mortality between baseline and 18 months. Logistic regression was used to explore baseline characteristics associated with mortality rate and with antipsychotic use at 18 months. At baseline, among 452 residents with PD, 72 (15.9%) received at least 1 antipsychotic drug. Mortality rates at 18 months in residents with PD with and without antipsychotic use were similar (34.3% and 38.2%, respectively, P = .58). Among factors associated with mortality, a statistically significant increase in mortality rate was found in very old residents (≥85 years of age) [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.3-3.1] or in those with chronic pulmonary disease (OR 3.6; 95% CI 1.5-8.5). Among residents ≥85 years of age, we also found a statistically significant increase in mortality rate in individuals with arterial hypertension (OR 2.8; 95% CI 1.3-5.8). Moreover, a statistically significant increase in prescription of antipsychotic drugs was found in residents who tried to elope (OR 3.8; 95% CI 1.4-10.7) and in those with severe psychiatric diseases (excluding depression) (OR 7.5; 95% CI 4.1-13.6). In this study investigating factors associated with mortality in old and very old residents with PD in NHs, no significant association was observed with the use of antipsychotics. However, our study suggests that age (≥85 years) or chronic pulmonary disease could be associated with mortality among

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

    Directory of Open Access Journals (Sweden)

    Saki Shimizu

    2015-04-01

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

  10. 'He was like a zombie': off-label prescription of antipsychotic drugs in dementia.

    Science.gov (United States)

    Harding, Rosie; Peel, Elizabeth

    2013-03-01

    This paper explores the legal position of the off-label prescription of antipsychotic medications to people with dementia who experience behavioural and psychological symptoms of dementia (BPSD). Dementia is a challenging illness, and BPSD can be very difficult for carers to manage, with evidence that this contributes to carer strain and can result in the early institutionalisation of people with dementia. As a result, the prescription of antipsychotic and other neuroleptic medications to treat BPSD has become commonplace, in spite of these drugs being untested and unlicensed for use to treat older people with dementia. In recent years, it has become apparent through clinical trials that antipsychotic drugs increase the risk of cerebrovascular accident (stroke) and death in people with dementia. In addition, these types of medication also have other risk factors for people with dementia, including over-sedation and worsening of cognitive function. Drawing on recent questionnaire (n = 185), focus group (n = 15), and interview (n = 11) data with carers of people with dementia, this paper explores the law relating to off-label prescription, and the applicability of medical negligence law to cases where adverse events follow the use of antipsychotic medication. It is argued that the practice of off-label prescribing requires regulatory intervention in order to protect vulnerable patients.

  11. Antipsychotic Drugs Rechallenge in Multi-antipsychotic Drug Induced Atypical Neuroleptic Malignant Syndrome: A Case of Cotard’s Syndrome

    Directory of Open Access Journals (Sweden)

    Helin Yılmaz

    2017-03-01

    Full Text Available Neuroleptic malignant syndrome (NMS is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics and characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. Cotard’s syndrome is characterized by the appearance of nihilistic delusions concerning one’s own body or life. By presenting this case, we aim to discuss the differential diagnosis and treatment plan of a patient with catatonia and Cotard’s syndrome, which were noted after NMS, in light of the literature.

  12. Antipsychotic Drugs Rechallenge in Multi-antipsychotic Drug Induced Atypical Neuroleptic Malignant Syndrome: A Case of Cotard’s Syndrome

    OpenAIRE

    Helin Yılmaz; N. Burcu Özbaran; Sezen Köse

    2017-01-01

    Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics and characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. Cotard’s syndrome is characterized by the appearance of nihilistic delusions concerning one’s own body or life. By presenting this case, we aim to discuss the differential diagnosis and treatment plan of a patient with catatonia and Cotard’s syndrome, which were noted af...

  13. Antipsychotic and Benzodiazepine Drug Changes Affect Acute Falls Risk Differently in the Nursing Home.

    Science.gov (United States)

    Berry, Sarah D; Placide, Sebastian G; Mostofsky, Elizabeth; Zhang, Yuqing; Lipsitz, Lewis A; Mittleman, Murray A; Kiel, Douglas P

    2016-02-01

    Psychotropic drugs increase the risk of falls, but they are still frequently prescribed to treat behavioral symptoms associated with dementia in the nursing home. We examined whether there is an acute increased risk of falls in the days following a change to an antipsychotic or benzodiazepine drug prescription. We collected information on 594 long-stay nursing home residents from two facilities who fell at least once between September 1, 2010 and May 31, 2013. Psychotropic drug changes were ascertained from the facilities' computerized medication administration log. We used the case-crossover design to compare the frequency of antipsychotic and benzodiazepine drug changes during the days before a fall with the frequency of drug changes at more remote times. Mean age was 87.5 years, and 75.1% were female. The risk of falls was higher in the 24 hours following benzodiazepine initiation compared with other times (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.10, 13.00). There was no clear difference in risk following antipsychotic initiation (OR 2.42, CI 0.58, 10.06), but this could be due to the small sample size. Stopping a benzodiazepine was associated with a significantly reduced fall risk (OR 0.26, 95% CI 0.08-0.91). Benzodiazepines pose an immediate threat to fall risk, whereas it is less clear if antipsychotics also pose an immediate risk. Nursing home staff should be particularly vigilant in the days following the new prescription for a benzodiazepine in an effort to prevent injury. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Margaret E. Mattson

    2015-01-01

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

  15. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial.

    Science.gov (United States)

    Anagnostou, Evdokia; Aman, Michael G; Handen, Benjamin L; Sanders, Kevin B; Shui, Amy; Hollway, Jill A; Brian, Jessica; Arnold, L Eugene; Capano, Lucia; Hellings, Jessica A; Butter, Eric; Mankad, Deepali; Tumuluru, Rameshwari; Kettel, Jessica; Newsom, Cassandra R; Hadjiyannakis, Stasia; Peleg, Naomi; Odrobina, Dina; McAuliffe-Bellin, Sarah; Zakroysky, Pearl; Marler, Sarah; Wagner, Alexis; Wong, Taylor; Macklin, Eric A; Veenstra-VanderWeele, Jeremy

    2016-09-01

    Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use. To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4

  16. Medical costs and hospitalizations among patients with depression treated with adjunctive atypical antipsychotic therapy: an analysis of health insurance claims data.

    Science.gov (United States)

    Halpern, Rachel; Nadkarni, Anagha; Kalsekar, Iftekhar; Nguyen, Hiep; Song, Rui; Baker, Ross A; Nelson, J Craig

    2013-01-01

    Depression is frequently debilitating. The American Psychiatric Association recommends adjunctive atypical antipsychotics as a treatment option when response to antidepressants is inadequate. To compare medical costs and hospitalizations among patients with depression treated with adjunctive aripiprazole, olanzapine, or quetiapine. This retrospective analysis used medical and pharmacy claims data and enrollment information from a large US health plan. Patients were adult members of a commercial health plan who were diagnosed with depression (ie, ICD-9-CM 296.2x, 296.3x, or 311) and who received an antidepressant with adjunctive atypical antipsychotic therapy (aripiprazole, olanzapine, or quetiapine) between January 1, 2004, and January 31, 2010. Patients were continuously enrolled for 6-month pre- and 12-month postaugmentation periods. Those with schizophrenia or bipolar disorder were excluded. Postaugmentation outcomes were total and mental health-related medical costs and hospitalizations. Costs and hospitalizations were modeled with generalized linear models (ie, gamma distribution, log link) and logistic regression, respectively. Regressions controlled for dose, demographics, and general and medical health-related health status. A total of 10,292 patients were identified across atypical antipsychotic cohorts: 3849 used aripiprazole, 1033 used olanzapine, and 5410 used quetiapine. Mean (SD) age was 44.1 (11.6) years and 70.3% were female. Compared with patients in the aripiprazole cohort, those in the olanzapine cohort had higher total medical costs (cost ratio [CR] 1.22, 95% CI 1.07-1.39) and higher mental health-related medical costs (CR 1.33, 95% CI 1.11-1.59), as well as higher odds of any (total) hospitalization (OR 1.58, 95% CI 1.30-1.92) and any mental health-related hospitalization (OR 1.81, 95% CI 1.38-2.38). Similarly, the quetiapine cohort had higher total medical costs (CR 1.27, 95% CI 1.16-1.39) and higher mental health-related medical costs (CR 1

  17. Evaluation of human D-amino acid oxidase inhibition by anti-psychotic drugs in vitro.

    Science.gov (United States)

    Shishikura, Miho; Hakariya, Hitomi; Iwasa, Sumiko; Yoshio, Takashi; Ichiba, Hideaki; Yorita, Kazuko; Fukui, Kiyoshi; Fukushima, Takeshi

    2014-06-01

    It is of importance to determine whether antipsychotic drugs currently prescribed for schizophrenia exert D-amino acid oxidase (DAO)-inhibitory effects. We first investigated whether human (h)DAO can metabolize D-kynurenine (D-KYN) to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence spectrometry. After confirmation of KYNA production from D-KYN by hDAO, 8 first- and second-generation antipsychotic drugs, and 6 drugs often prescribed concomitantly, were assayed for hDAO-inhibitory effects by using in vitro fluorometric methods with D-KYN as the substrate. DAO inhibitors 3-methylpyrazole-5-carboxylic acid and 4H-thieno[3,2-b]pyrrole-5-carboxylic acid inhibited KYNA production in a dose-dependent manner. Similarly, the second-generation antipsychotics blonanserin and risperidone were found to possess relatively strong hDAO-inhibitory effects in vitro (5.29 ± 0.47 μM and 4.70 ± 0.17 μM, respectively). With regard to blonanserin and risperidone, DAO-inhibitory effects should be taken into consideration in the context of their in vivo pharmacotherapeutic efficacy.

  18. Antipsychotic drug effects on brain morphology in first-episode psychosis.

    Science.gov (United States)

    Lieberman, Jeffrey A; Tollefson, Gary D; Charles, Cecil; Zipursky, Robert; Sharma, Tonmoy; Kahn, Rene S; Keefe, Richard S E; Green, Alan I; Gur, Raquel E; McEvoy, Joseph; Perkins, Diana; Hamer, Robert M; Gu, Hongbin; Tohen, Mauricio

    2005-04-01

    Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). Patients with first-episode psychosis (DSM-IV) and healthy volunteers. Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). Brain volume changes assessed by MRI. Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses

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

    Science.gov (United States)

    2015-10-01

    Atypical antipsychotics (AAP) are prescribed to patients with autism spectrum disorders with symptoms of aggression or agitation, stereotypic behavior...Atypical antipsychotics (AAP) are used chronically to treat millions of pediatric, adult, and geriatric patients with schizophrenia , bipolar disorder

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

    Directory of Open Access Journals (Sweden)

    José María Rico-Gomis

    2016-07-01

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

  1. 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.......7% for elderly patients with dementia, with a national incidence of 3.9%. The prevalence ranged from 17.0% to 23.3% in the five regions and from 7.5% to 33.1% in the 98 municipalities, demonstrating an over four-fold difference. CONCLUSION: The observed geographical variation was more pronounced at municipal...

  2. Comparative efficacy and acceptability of combined antipsychotics and mood stabilizers versus individual drug classes for acute mania: Network meta-analysis.

    Science.gov (United States)

    Glue, Paul; Herbison, Peter

    2015-12-01

    Recent network meta-analyses of drug treatments for acute mania have only evaluated the efficacy and acceptability of individual drug treatments. The relative efficacy and acceptability of combined drug treatment has not been assessed. Double-blind drug trials in acute mania were identified using a systematic search strategy. We recorded numbers of patients enrolled, endpoints for efficacy (changes in mania rating scales, numbers of responders) and acceptability (numbers of dropouts) and treatment administered (categorized as antipsychotic, mood stabilizer, combined antipsychotic/mood stabilizer or placebo). Data were analyzed using a random effects frequentist network meta-analysis. All three drug categories were more effective than placebo. Antipsychotics and combined antipsychotic/mood stabilizer were significantly more effective than mood stabilizers for changes in mania rating scales. Combined antipsychotic/mood stabilizer was significantly more effective than mood stabilizers and antipsychotics for responder rate. Dropout rates were significantly lower for antipsychotics compared with placebo and mood stabilizers. Combined antipsychotic/mood stabilizer had the highest probability of being the best treatment based on change in mania rating scales (96.1% for all mania scales; 85.5% for Young Mania Rating Scale), and 99.3% for being the best treatment for responders. Antipsychotics had 82.0% probability as the best treatment to minimize dropouts. Combined antipsychotic/mood stabilizer appears to have efficacy advantages over antipsychotic or mood stabilizer monotherapy in acute mania, and should be considered as first line therapy. © The Royal Australian and New Zealand College of Psychiatrists 2015.

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

    Science.gov (United States)

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

    2017-08-03

    To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, pdisability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013). Differences in rates of movement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study.

    Science.gov (United States)

    Volavka, Jan; Czobor, Pál; Citrome, Leslie; Van Dorn, Richard A

    2014-10-01

    Aggressive behavior can be a dangerous complication of schizophrenia. Hostility is related to aggression. This study aimed to compare the effects of olanzapine, perphenazine, risperidone, quetiapine, and ziprasidone on hostility in schizophrenia. We used the data that were acquired in the 18-month Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. We analyzed the scores of the Positive and Negative Syndrome Scale (PANSS) hostility item in a subset of 614 patients who showed at least minimal hostility (a score ≥ 2) at baseline. The primary analysis of hostility indicated an effect of difference between treatments (F(4,1487) = 7.78, P schizophrenia enrolled in the European First-Episode Schizophrenia Trial (EUFEST) trial, where olanzapine demonstrated advantages compared with haloperidol, quetiapine, and amisulpride. Olanzapine demonstrated advantages in terms of a specific antihostility effect over the other antipsychotics tested in Phase 1 of the CATIE trial.

  5. Physicians' reasons not to discontinue long-term used off-label antipsychotic drugs in people with intellectual disability

    NARCIS (Netherlands)

    de Kuijper, G. M.; Hoekstra, P. J.

    2017-01-01

    Background: People with intellectual disability (ID) frequently use antipsychotic drugs on an off-label base, often for many years. Physicians' decisions to discontinue these drugs not only depend on patient characteristics, like the presence of mental or behavioural disorders, but also on

  6. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects?

    Science.gov (United States)

    Raeder, Maria B; Fernø, Johan; Vik-Mo, Audun O; Steen, Vidar M

    2006-09-01

    Drug-induced weight gain is a major problem in the treatment of psychiatric disorders, especially with some antipsychotic- and antidepressant drugs. We have recently demonstrated that antipsychotic- and antidepressant drugs activate the SREBP (sterol regulatory element-binding proteins) transcription factors in human- and rat glial cells, with subsequent up-regulation of downstream genes involved in cholesterol- and fatty acid biosynthesis. Since stimulation of cellular lipogenesis in the liver could be of relevance for the metabolic side effects of these drugs, we have now investigated the effects of antidepressants, antipsychotic- and mood-stabilizing drugs on cell cultures of human liver cells. For several of the drugs being strongly associated with weight gain (clozapine, imipramine, and amitriptyline), we observed a very pronounced activation of SREBP. Ziprasidone and buproprion, however, which are not associated with weight gain, did hardly stimulate the SREBP system. For haloperidol, olanzapine and mirtazapine, the correspondence between metabolic side effects and SREBP stimulation in liver cells was less obvious. The mood-stabilizers did not increase SREBP activation. The results indicate a relationship between drug-induced activation of SREBP in cultured human liver cells and weight gain side-effects of antidepressant and antipsychotic drugs.

  7. Intent-to-treat analysis of health care expenditures of patients treated with atypical antipsychotics as adjunctive therapy in depression.

    Science.gov (United States)

    Jing, Yonghua; Kalsekar, Iftekhar; Curkendall, Suellen M; Carls, Ginger S; Bagalman, Erin; Forbes, Robert A; Hebden, Tony; Thase, Michael E

    2011-09-01

    To compare health care utilization and expenditures in patients with depression whose initial antidepressant (AD) treatment was augmented with a second-generation antipsychotic. Claims data from January 1, 2001, through June 30, 2009, were used to select patients aged 18 to 64 years with depression treated with ADs augmented with aripiprazole, olanzapine, or quetiapine. Patients were required to have 6 months of continuous eligibility before the first AD prescription and 6 months after the second-generation antipsychotic augmentation (index) date. Utilization and expenditures were assessed for 6 months after the index date. Multivariate regression was used to estimate adjusted expenditures and risks for hospitalizations and emergency department visits. A total of 483 patients treated with aripiprazole, 978 with olanzapine, and 2471 with quetiapine were selected. Mean adjusted expenditures for aripiprazole were significantly lower than those for olanzapine for each service category (all-cause, all-cause medical care, mental health-related, and mental health-related medical care) and were significantly lower than those for quetiapine for each category with the exception of mental health-related. The adjusted risks for hospitalization and emergency department visits were significantly higher for quetiapine than for aripiprazole. Compared with patients treated with ADs and aripiprazole, those treated with ADs and olanzapine or quetiapine had greater utilization and higher expenditures. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  8. 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.

    Science.gov (United States)

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila; Frimurer, Thomas; Schwartz, Thue W; Levy, Finn Olav; Andressen, Kjetil Wessel

    2015-07-15

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We 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-mediated degradation of 5-HT7 receptors and also interfered with G protein activation. In addition, we tested whether receptor degradation was mediated by the GPCR-associated sorting protein-1 (GASP-1). We show that GASP-1 binds the 5-HT7 receptor and regulates the clozapine-mediated degradation. Mutations of the identified motifs and residues, located in or close to Helix-VIII of the 5-HT7 receptor, modified antipsychotic-stimulated binding of proteins (such as GASP-1), possibly by altering the flexibility of Helix-VIII, and also interfered with G protein activation. Taken together, our data demonstrate that binding 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.

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

    Science.gov (United States)

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

    2008-03-01

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

  10. 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

    risperidone (n = 14,134). The primary outcome was any major cardiovascular event (composite of cardiovascular mortality, acute coronary syndrome, or ischemic stroke) within 1 year following treatment initiation. Cox regression was used to estimate hazard ratios (HRs) while on current antipsychotic monotherapy...... in the outpatient setting, adjusting for an outcome-specific disease risk score. RESULTS: The crude rate of any major cardiovascular event was 5.3 per 1,000 person-years among olanzapine users, 3.4 in quetiapine users, and 5.2 in risperidone users. Compared with risperidone, the risk of any major cardiovascular.......9 to 2.0) events for quetiapine. CONCLUSIONS: Among young and middle-aged outpatients, the risk of acute major cardiovascular events was similar with use of olanzapine, quetiapine, and risperidone. Although moderate relative differences cannot be ruled out, any differences are small in absolute terms....

  11. Synthesis of [sup 3]H- and [sup 14]C-labelled CP-88,059: a potent atypical antipsychotic agent

    Energy Technology Data Exchange (ETDEWEB)

    Howard, H.R.; Shenk, K.D.; Smolarek, T.A. (Pfizer Inc., Groton, CT (United States). Central Research Div.); Marx, M.H.; Windels, J.H.; Roth, R.W. (Chemsyn Science Labs., Lenexa, KS (United States))

    1994-02-01

    CP-88,059 is a combined D[sub 2]/5-HT[sub 2] antagonist currently undergoing clinical evaluation as an antipsychotic agent with reduced potential for induction of EPS in schizophrenic patients. Displacement of bromine from the 7-position of the benzisothiazole moeity, by reductive dehydrogenation with tritium gas and Pd/BaSO[sub 4] catalysis, provided [sup 3]H-CP-88,059. Incorporation of [sup 14]C into the ethylene portion of the molecule was achieved via the Friedel-Crafts acylation of 6-chlorooxindole with [2-[sup 14]C]-chloroacetyl chloride, followed by triethylsilane reduction of the aryl carbonyl and coupling with N-(1,2-benzisothiazol-3-yl)piperazine in refluxing aqueous Na[sub 2]CO[sub 3]. (author).

  12. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe.

    Directory of Open Access Journals (Sweden)

    Emanuel Raschi

    Full Text Available BACKGROUND: Antipsychotics (APs have been associated with risk of torsade de Pointes (TdP. This has important public health implications. Therefore, (a we exploited the public FDA Adverse Event Reporting System (FAERS to characterize their torsadogenic profile; (b we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010 were analyzed based on the following criteria: (1 ≥ 4 cases of TdP/QT abnormalities; (2 Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers; (3 ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD; (4 Significant ROR for VA/SCD; (5 Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled to group E (unclear/uncertain signal: only 2/5 criteria. Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID. RESULTS: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone. In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia to 13.99 (France, 2009. Considerable increment of Group A agents was found in several Countries (+3.47 in France: the exposure to olanzapine increased across all Countries (+1.84 in France and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009. Among Group B drugs, levomepromazine peaked 3.78 (Serbia; fluphenazine 1.61 (Slovenia. CONCLUSIONS: This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  13. Risk of ischemic stroke associated with the use of antipsychotic drugs in elderly patients: a retrospective cohort study in Korea.

    Directory of Open Access Journals (Sweden)

    Ju-Young Shin

    Full Text Available Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs and atypical antipsychotics (AAPs. This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs.We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine and those prescribed the AAPs (risperidone, quetiapine, or olanzapine. We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63 were identified. The hazard ratios (HR for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference.Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97-5.38, which was followed by haloperidol (HR = 2.43, 95% CI, 1.18-3.14, quetiapine (HR = 1.23, 95% CI, 0.78-2.12, and olanzapine (HR = 1.12, 95% CI, 0.59-2.75. Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83-6.02 than those who took it for a shorter period of time.A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics.

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

    Directory of Open Access Journals (Sweden)

    Irismar Reis de Oliveira

    2009-03-01

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

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

    Science.gov (United States)

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

    2017-07-14

    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.

  16. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study.

    Science.gov (United States)

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun; Bahk, Won-Myong

    2016-07-01

    The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, pblonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP.

  17. Does the use of atypical antipsychotics as adjunctive therapy in depression result in cost savings? Comparing healthcare costs and utilization between second-line treatment options.

    Science.gov (United States)

    Hassan, Amany K; Farmer, Kevin C; Brahm, Nancy C; Keast, Shellie; Nesser, Nancy; Neas, Barbara R

    2016-12-01

    Several atypical antipsychotics (AAPs) are used as second-line agents for treatment resistant depression. AAPs can be expensive compared to other treatment options and can cause several side effects. To estimate healthcare costs and utilization of AAPs compared to other second-line agents. Observational study using Medicaid claims data (2006-2011). Subjects were depression-diagnosed adult members with at least two prescriptions of antidepressant medications followed by a second-line agent. Gamma generalized linear models (GLM) produced estimates of the difference in mean expenditures among treatment groups after adjusting for individual baseline characteristics using propensity scores. Negative binomial models produced estimates of the difference in number of hospitalizations and emergency department (ED) visits. A total of 3910 members received second-line treatment. Treatment groups were AAPs (n = 2211), augmentation agents other than AAPs (n = 1008), and antidepressant switching (n = 691). AAPs resulted in higher mean adjusted pharmacy costs and higher mean adjusted total mental health-related costs. Mean adjusted total healthcare costs and number of inpatient and ED visits were not different among treatments. The results show no evidence that AAPs used as second-line treatment for depression results in overall cost savings or lower inpatient and ED visits compared to other treatment strategies.

  18. A Systematic Review of Atypical Antipsychotics in Chronic Pain Management: Olanzapine Demonstrates Potential in Central Sensitization, Fibromyalgia, and Headache/Migraine.

    Science.gov (United States)

    Jimenez, Xavier F; Sundararajan, Tharani; Covington, Edward C

    2017-10-26

    Many psychopharmacologic agents are used as primary or adjunct agents in pain management. Atypical antipsychotics (AAs) have also been used as adjuncts in pain management regimens in a variety of manners; however, their efficacy in this capacity is unclear. A systematic review of all studies examining AA use for pain was conducted. Three literature databases were utilized to search for word combinations of "pain" and a variety of commonly-prescribed AAs (olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, clozapine, paliperidone, iloperidone, lurasidone). Articles chosen for review included retrospective analyses, randomized control trials, and case series/reports. A PRISMA diagram illustrates the study selection process. Olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone are the only AAs with published studies in pain syndromes. Of these, olanzapine and quetiapine have the most combined studies (11 and 6, respectively). Olanzapine shows preliminary and consistent efficacy in fibromyalgia and headache/migraine, although only one study was a randomized controlled trial with Level I evidence of efficacy. Other AAs (quetiapine included) fail to demonstrate efficacy in pain syndromes and/or lack robust study designs. Few studies have been conducted to evaluate the analgesic effects of AAs. The collective findings of multiple studies evaluating olanzapine in pain syndromes suggest a high yet preliminary level of evidence of efficacy, warranting prospective studies in various pain syndrome contexts. Pharmacological mechanisms of AA action are elaborated, and the findings of this review are discussed. Risk and benefits of using AAs in chronic pain are elaborated, and investigational implications and future directions are explored.

  19. Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2008-01-01

    Full Text Available INTRODUCTION Olanzapine is a second generation antipsychotic (SGA with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline was associated with good initial response (PANSS reduction 20% in the first two weeks and the improvement was maintained further on (PANSS reduction 50% after 16 weeks. Significant increase (20 kg, 40% in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2. CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

  20. A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment.

    Science.gov (United States)

    Dilly, Suzanne J; Clark, Andrew J; Marsh, Andrew; Mitchell, Daniel A; Cain, Ricky; Fishwick, Colin W G; Taylor, Paul C

    2017-05-01

    Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag ® chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17-β-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-β-HSD10 identifies risperidone as a drug reprofiling candidate. When formulated with rumenic acid, risperidone slows proliferation of PC3 prostate cancer cells in vitro and retards PC3 prostate cancer tumour growth in vivo in xenografts in mice, presenting an opportunity to reprofile risperidone as a cancer treatment. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  1. [Improve safety monitoring of antipsychotics in the French pediatric population].

    Science.gov (United States)

    Menard, M-L; Askenazy, F; Auby, P; Bonnot, O; Cohen, D

    2015-01-01

    In France, as in the rest of the world, the prescription of second generation antipsychotics is on the rise in the pediatric population. At the same time, the use of first generation antipsychotics continues, although it is declining in France as in other countries. In France, we lack data on the pediatric population to ensure a safe prescription, unlike other countries such as Canada and the United States. This is disturbing when many adverse events, potentially serious for young patients' health (neuromuscular complications, risk factors, cardiovascular problems) are beginning to be identified. This article reports the current French and international knowledge on antipsychotics in the pediatric population. It appears that data in the French population are nearly nonexistent and that the methodological tools used are not always relevant (population already exposed to psychotropic drugs, short studies, debatable rating scale and somatic parameters). Within this context, a safety monitoring procedure for the naive pediatric population treated with antipsychotics was developed (ETAPE study) to determine the incidence of adverse events appearing with these drugs. Safety monitoring during the 12-month study period will include clinical assessments and laboratory testing. These assessments will be performed before treatment and at 1, 3, 6, 9, and 12 months after the introduction of the antipsychotic drug. This study received funding from the National Security Agency of Medicines (ANSM 2012 No. 40). The results should contribute to educating all practitioners (general physicians, pediatricians, psychiatrists, child psychiatrists) on adverse events, helping practitioners with prescribing decisions, reinforcing the French system of monitoring adverse events caused by atypical antipsychotic drugs, and developing recommendations to improve the safety of atypical antipsychotic drugs in child psychiatry. Copyright © 2014. Published by Elsevier SAS.

  2. Can antipsychotic drugs be classified by their effects on a particular group of dopamine neurons in the brain?

    NARCIS (Netherlands)

    Westerink, BHC

    2002-01-01

    During the four decades that research has been carried out on antipsychotic drugs, a variety of methods have been used to study the effects of these compounds on dopamine neurotransmission. An important issue in this research was to find an explanation for the difference between "typical" and

  3. Practical Guidelines for the Use of New Generation Antipsychotic Drugs (except Clozapine) in Adult Individuals with Intellectual Disabilities

    Science.gov (United States)

    de Leon, Jose; Greenlee, Brian; Barber, Jack; Sabaawi, Mohamed; Singh, Nirbhay N.

    2009-01-01

    New generation antipsychotic (NGA) drugs introduced to the US market after clozapine (aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) are frequently used in individuals with intellectual disabilities (ID). However, there is very limited research to fully establish evidence-based or personalized medicine approaches…

  4. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

    NARCIS (Netherlands)

    Westerink, B.H.C.; Kawahara, Y; de Boer, P; Geels, C; de Vries, J.B; Wikström, H.V; van Kalkeren, A; van Vliet, B; Kruse, C.H; Long, S.K

    2001-01-01

    Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in

  5. The antagonistic effect of antipsychotic drugs on a HEK293 cell line stably expressing human alpha(1A1)-adrenoceptors

    DEFF Research Database (Denmark)

    Nourian, Zahra; Mulvany, Michael J; Nielsen, Karsten Bork

    2008-01-01

    Antipsychotic drugs often cause orthostatic hypotension, probably through antagonist action on resistance vessel alpha(1A)-adrenoceptors. Here we have tested this possibility directly using cells transfected with a relevant human alpha(1A)-adrenoceptor splice variant. To determine a splice variant...

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

    Directory of Open Access Journals (Sweden)

    Acioly LT Lacerda

    2002-03-01

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

  7. Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.

    Science.gov (United States)

    Jeyaseeli, L; Dasgupta, A; Dastidar, S G; Molnar, J; Amaral, L

    2012-06-01

    Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp.

  8. Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model.

    Science.gov (United States)

    Furiak, Nicolas M; Gahn, James C; Klein, Robert W; Camper, Stephen B; Summers, Kent H

    2012-11-16

    The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements

  9. Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model

    Directory of Open Access Journals (Sweden)

    Furiak Nicolas M

    2012-11-01

    Full Text Available Abstract The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms. A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill. Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT and once-monthly risperidone long-acting injection (RIS-LAI with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total and are estimated for LFA therapies given at three, six, and nine month intervals. The one-year results show that LFA therapy every 3 months (LFA-3 ($6,088 is less costly than either RIS-SOT ($10,721 or RIS-LAI ($9,450 with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41. Extending the interval to six (LFA-6 and nine (LFA-9 months resulted in further reductions in relapse and costs. Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health

  10. Learning and generalization in schizophrenia: effects of disease and antipsychotic drug treatment.

    Science.gov (United States)

    Shohamy, Daphna; Mihalakos, Perry; Chin, Ronald; Thomas, Binu; Wagner, Anthony D; Tamminga, Carol

    2010-05-15

    Schizophrenia involves alterations in hippocampal function. The implications of these alterations for memory function in the illness remain poorly understood. Furthermore, it remains unknown how memory is impacted by drug treatments for schizophrenia. The goal of this study was to delineate specific memory processes that are disrupted in schizophrenia and explore how they are affected by medication. We specifically focus on memory generalization--the ability to flexibly generalize memories in novel situations. Individuals with schizophrenia (n = 56) and healthy control subjects (n = 20) were tested on a computerized memory generalization paradigm. Participants first engaged in trial-by-error associative learning. They were then asked to generalize what they learned by responding to novel stimulus combinations. Individuals with schizophrenia were tested on or off antipsychotic medication, using a between-subject design in order to eliminate concerns about learning-set effects. Individuals with schizophrenia were selectively impaired in their ability to generalize knowledge, despite having intact learning and memory accuracy. This impairment was found only in individuals tested off medication. Individuals tested on medication generalized almost as well as healthy control subjects. This between-group difference was selective to memory generalization. These findings suggest that individuals with schizophrenia have a selective alteration in the ability to flexibly generalize past experience toward novel learning environments. This alteration is unaccompanied by global memory impairments. Additionally, the results indicate a robust generalization difference on the basis of medication status. These results suggest that hippocampal abnormalities in schizophrenia might be alleviated with antipsychotic medication, with important implications for understanding adaptive memory-guided behavior. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Lefebvre, Patrick; Muser, Erik; Joshi, Kruti; DerSarkissian, Maral; Bhak, Rachel H; Duh, Mei Sheng; Shiner, Brian; Young-Xu, Yinong

    2017-07-01

    Almost half of all patients diagnosed with schizophrenia have a history of substance abuse (SA). However, data on treatment of schizophrenia with paliperidone palmitate (PP) among patients with comorbid SA are limited. The objective of this study was to compare all-cause and SA-related health care resource utilization and costs in veterans with schizophrenia and co-occurring SA who were treated with PP versus oral atypical antipsychotics (OAAs). Veterans Health Administration electronic health record data were used to conduct a retrospective longitudinal study in veterans with schizophrenia who initiated PP or OAA between January 1, 2010 and June 30, 2016, had ≥12 months of enrollment before treatment initiation (baseline), were diagnosed with SA, and had ≥1 Global Assessment of Functioning score during baseline. Differences in baseline characteristics were adjusted for using inverse probability of treatment weighting. Adjusted cost differences and incidence rate ratios (IRR) for the association between PP versus OAA and all-cause and SA-related health care costs and health care resource utilization in the 12 months after treatment initiation were estimated with corresponding 95% CIs using weighted linear and Poisson regression models, respectively. Of 6872 veterans in the study, 1684 (25%) and 5188 (75%) were treated with PP and OAA, respectively. After adjustment, PP was associated with fewer all-cause inpatient (IRR = 0.88; 95% CI, 0.85 to 0.90), mental health-related inpatient (IRR = 0.88; 95% CI, 0.85 to 0.91), and long-term care stays (IRR = 0.53; 95% CI, 0.44 to 0.64), but more frequent mental health intensive case management visits (IRR = 1.51; 95% CI, 1.49 to 1.53) compared with OAA (all P schizophrenia and comorbid SA. Thus, PP appears to be a valuable treatment option for patients in this subpopulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Atypical charles bonnet syndrome

    OpenAIRE

    Priti Arun; Rajan Jain; Vaibhav Tripathi

    2013-01-01

    Charles Bonnet syndrome (CBS) is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  14. A short term prospective study of the effects of the commonly used antipsychotic drugs on ECG parameters

    Directory of Open Access Journals (Sweden)

    Aditya A Pandurangi

    2015-01-01

    Full Text Available Context: Psychiatric patients have been identified as a population at risk for cardiovascular problems. Mortality rates are higher among psychiatric patients than in the general population and pharmacological treatment may produce side-effects that affect morbidity and mortality. Most of the previous studies are cross-sectional and are done without taking the base line values and they do not mention clearly the effects of antipsychotic drugs when used for a short period. Aims: To compare the effects of Olanzapine (OLZ, Risperidone (RSP, Trifluperazine (TFP and Haloperidol (HPL antipsychotic drugs on various ECG Parameters. Settings and Design: Short term prospective study. Materials and Methods: All the consecutive patients attending the hospital, who mandated the use of antipsychotic drugs, were recruited. A baseline electrocardiogram (ECG was recorded on Day 0, before starting the antipsychotic drug. ECGs were repeated on Days 1, 5 and 10 after starting the drug. A total of 71 patients were included (N = 71, of which 33 were in OLZ group (N = 33, 14 in the RSP group (N = 14, 13 in the TFP group (N = 13 and 11 in HPL group (N = 11. Statistical analysis used: The data was analysed using SPSS Ver. 14 software. Results: No statistically significant differences were found in the ECG parameters in patients on OLZ, RSP, TFP and HPL. Conclusions: Our study shows that there are no significant changes in ECG parameters after administration of OLZ, RSP, TFP and HPL. Thus all the four drugs are equally safe in healthy adults for short-term use.

  15. [Antipsychotics in bipolar disorders].

    Science.gov (United States)

    Vacheron-Trystram, M-N; Braitman, A; Cheref, S; Auffray, L

    2004-01-01

    This article is a review of the various treatments that are currently available, in particular in France, for the treatment of bipolar disorders. This article specifically addresses the use of novel antipsychotic agents as alternative therapy to a lithium therapy and/or the use of conventional antipsychotics. The prevalence of bipolar disorder over a lifetime is around 1% of the general population. Bipolar disorder consists of alternating depressive and manic episodes. It mainly affects younger subjects, and is often associated with alcohol and drug addictions. There are two main subtypes of bipolar disorder. According to the DSM IV-R, type 1 of bipolar disorder is characterised when at least one manic episode (or a mixed episode) has been diagnosed. Type 2 of bipolar disorder is related to patients enduring recurrent depressive episodes but no manic episode. Type 2 affects women more frequently as opposed to type 1 affecting individuals of both sexes. Manic-depressive disorder (or cyclo-thymic disorder) appears in relation to patients who has never suffered manic episode, mixed episode or severe depressive episode but have undergone numerous periods with some symptoms of depression and hypomanic symptoms over a two-year period during which any asymptomatic periods last no longer than two months. The average age of the person going through a first episode (often a depressive one) is 20 years-old. Untreated bipolar patients may endure more than ten manic or depressive episodes. Finally, in relation to 10 to 20% of patients, the bipolar disorder will turn into a fast cycle form, either spontaneously or as a result of certain medical treatments. Psychiatrists are now able to initiate various treating strategies which are most likely to be effective as a result of the identification of clinical subtypes of the bipolar disorder. Lithium therapy has been effectively and acutely used for patients with pure or elated mania and its prophylaxis. However, lithium medication

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

    Directory of Open Access Journals (Sweden)

    M. Mohanalakshmi

    2017-03-01

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

  17. Social feeding in Caenorhabditis elegans is modulated by antipsychotic drugs and calmodulin and may serve as a protophenotype for asociality.

    Science.gov (United States)

    Dwyer, Donard S; Awatramani, Poonam; Thakur, Rashmi; Seeni, Ramya; Aamodt, Eric J

    2015-05-01

    Here, we define a protophenotype as an endophenotype that has been conserved during evolution. Social feeding in Caenorhabditis elegans may be an example of a protophenotype related to asociality in schizophrenia. It is regulated by the highly conserved neuropeptide Y receptor, NPR-1, and we speculated that social feeding should be affected by antipsychotic drugs. The social feeding strain, npr-1(g320), was exposed to antipsychotic drugs, dopamine or calmodulin antagonists on plates with bacterial lawns, and the number of aggregates on the plates was counted as a measure of social feeding. First-generation antipsychotics, chlorpromazine, trifluoperazine, fluphenazine, and haloperidol, and the second-generation drug, olanzapine, inhibited social feeding. Dopamine accelerated aggregation, whereas selective D2 dopamine receptor antagonists, sulpiride and raclopride, were inhibitory. Calmodulin antagonists effectively inhibited social feeding, as did RNAi knockdown of calmodulin (cmd-1) expression. In addition, gap junction inhibitors prevented aggregation, which is consistent with the hub-and-spoke arrangement of neurons that regulate social feeding via functional gap junctions. The studies described here revealed novel connections between dopaminergic signaling, the NPY receptor, calmodulin, and gap junctions in the regulation of social behavior in C. elegans. These pathways are evolutionarily-conserved, and have also been implicated in the pathogenesis of schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y1 and P2Y12 Receptors

    Directory of Open Access Journals (Sweden)

    Chang-Chieh Wu

    2016-01-01

    Full Text Available Antipsychotic drugs (APDs used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM. Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP receptors, P2Y1 and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1 receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats’ platelets, as assessed by in vitro or ex vivo approach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats’ platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms.

  19. Social memory in mice: disruption with an NMDA antagonist and attenuation with antipsychotic drugs.

    Science.gov (United States)

    Gao, Xue-Min; Elmer, Gregory I; Adams-Huet, Beverley; Tamminga, Carol A

    2009-04-01

    Social recognition reflects the ability of one animal to learn and remember the identity of another. Animal models of social learning and memory are pertinent to several different CNS diseases involving disruptions in cognition. Moreover, the increased understanding of the basic biology of memory increases the likelihood of discovery of memory-enhancing treatments in these human diseases. In the present study, we investigated the effects of the non-competitive NMDA antagonist ketamine on social recognition in mice across a broad dose range (5-30 mg/kg) and time-course (60 min-7 days). We also tested the ability of two antipsychotic drugs, haloperidol and olanzapine, to block the ketamine effect. Our results show that mice demonstrate social recognition over a several day period, with loss of recognition between 3-7 days. Ketamine disrupts social memory at doses which do not affect task performance. Chronic oral administration of haloperidol or olanzapine attenuates these ketamine-induced effects on social recognition, tending to normalize the memory behavior. The neural mechanisms of these actions are not known, although medial temporal lobe memory systems have been implicated.

  20. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy.

    Science.gov (United States)

    Wu, Chia-Hsien; Bai, Li-Yuan; Tsai, Ming-Hsui; Chu, Po-Chen; Chiu, Chang-Fang; Chen, Michael Yuanchien; Chiu, Shih-Jiuan; Chiang, Jo-Hua; Weng, Jing-Ru

    2016-06-09

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy.

  1. Immediate-Early Genes Modulation by Antipsychotics: Translational Implications for a Putative Gateway to Drug-Induced Long-Term Brain Changes

    Directory of Open Access Journals (Sweden)

    Andrea de Bartolomeis

    2017-12-01

    Full Text Available An increasing amount of research aims at recognizing the molecular mechanisms involved in long-lasting brain architectural changes induced by antipsychotic treatments. Although both structural and functional modifications have been identified following acute antipsychotic administration in humans, currently there is scarce knowledge on the enduring consequences of these acute changes. New insights in immediate-early genes (IEGs modulation following acute or chronic antipsychotic administration may help to fill the gap between primary molecular response and putative long-term changes. Moreover, a critical appraisal of the spatial and temporal patterns of IEGs expression may shed light on the functional “signature” of antipsychotics, such as the propensity to induce motor side effects, the potential neurobiological mechanisms underlying the differences between antipsychotics beyond D2 dopamine receptor affinity, as well as the relevant effects of brain region-specificity in their mechanisms of action. The interest for brain IEGs modulation after antipsychotic treatments has been revitalized by breakthrough findings such as the role of early genes in schizophrenia pathophysiology, the involvement of IEGs in epigenetic mechanisms relevant for cognition, and in neuronal mapping by means of IEGs expression profiling. Here we critically review the evidence on the differential modulation of IEGs by antipsychotics, highlighting the association between IEGs expression and neuroplasticity changes in brain regions impacted by antipsychotics, trying to elucidate the molecular mechanisms underpinning the effects of this class of drugs on psychotic, cognitive and behavioral symptoms.

  2. Efficacy and safety of blonanserin versus other antipsychotics: a review

    OpenAIRE

    Anant D. Patil

    2013-01-01

    Although many atypical antipsychotics are available, there is a need of an atypical antipsychotic effective in all symptom domains of schizophrenia and well tolerated especially for side effects like extrapyramidal side effects, weight gain and blood prolactin elevation. Blonanserin is an atypical antipsychotic which blocks dopamine D2 and serotonin 5HT2A receptors. Its efficacy and safety has been studied in patients with schizophrenia and delirium. Blonanserin is found to be effective and w...

  3. Atypical Antipsychotics and the Risks of Acute Kidney Injury and Related Outcomes Among Older Adults: A Replication Analysis and an Evaluation of Adapted Confounding Control Strategies.

    Science.gov (United States)

    Ryan, Patrick B; Schuemie, Martijn J; Ramcharran, Darmendra; Stang, Paul E

    2017-03-01

    A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32-1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78-1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may

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

    Directory of Open Access Journals (Sweden)

    Zhang-Jin Zhang

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

  5. Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model: influence of non-cardiac α₁-adrenergic receptors.

    Science.gov (United States)

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

    2015-02-05

    Torsades de Pointes (TdP) is a potentially lethal cardiac arrhythmia and a known adverse effect of many drugs secondary to block of the rapidly activating delayed rectifier potassium current (IKr). In animal models antipsychotic drugs have shown reduced pro-arrhythmic potential compared to drugs with comparable IKr-blocking characteristics. The reduced pro-arrhythmic properties of antipsychotic drugs has been attributed to a variety of different causes e.g., effects on α₁-adrenergic receptors, β-adrenergic receptors, muscarinic receptors or cardiac ion channels like Ca(2+)- and Na(+)-channels. Since only 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 for the first time in an in vivo pro-arrhythmic rabbit model that several antipsychotic drugs in accordance with their known α₁-adrenergic receptor blocking properties reduced the incidence of drug-induced TdP and that the overall ability of the antipsychotic drugs to prevent TdP was associated with prevention of methoxamine induced increase in blood pressure. Further investigations are required to clarify the relative importance of α₁-adrenergic receptor antagonism in conjunction with the additional effects of antipsychotic drugs on various receptors and ion channels. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    Vik-Mo Audun O

    2006-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Mihoko Hagiwara

    2016-09-01

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

  8. Prevalence and correlates of atypical patterns of drug use progression

    African Journals Online (AJOL)

    alcohol, tobacco, and cannabis is associated with increased ... was the use of extra-medical drugs prior to alcohol and tobacco. Gender ...... Morelos, Mexico. Drug and Alcohol Dependence 2005; 77: 93-96. 10. Brecht ML, Greenwell L, Anglin MD. Substance use pathways to methamphetamine use among treated users.

  9. Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia.

    Science.gov (United States)

    Barber, Sarah; Olotu, Uwaila; Corsi, Martina; Cipriani, Andrea

    2017-03-23

    Between 40% and 70% of people with treatment-resistant schizophrenia do not respond to clozapine, despite adequate blood levels. For these people, a number of treatment strategies have emerged, including the prescription of a second anti-psychotic drug in combination with clozapine. To determine the clinical effects of various clozapine combination strategies with antipsychotic drugs in people with treatment-resistant schizophrenia both in terms of efficacy and tolerability. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (to 28 August 2015) and MEDLINE (November 2008). We checked the reference lists of all identified randomised controlled trials (RCT). For the first version of the review, we also contacted pharmaceutical companies to identify further trials. We included only RCTs recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug. We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and 95% confidence intervals (CI) on an intention-to-treat basis using a random-effects meta-analysis. For continuous data, we calculated mean differences (MD) and 95% CIs. We used GRADE to create 'Summary of findings' tables and assessed risk of bias for included studies. We identified two further studies with 169 participants that met our inclusion criteria. This review now includes five studies with 309 participants. The quality of evidence was low, and, due to the high degree of heterogeneity between studies, we were unable to undertake a formal meta-analysis to increase the statistical power.For this update, we specified seven main outcomes of interest: clinical response in mental state (clinically significant response, mean score/change in mental state), clinical response in global state (mean score/change in global state), weight

  10. The role of thermogenesis in antipsychotic drug-induced weight gain.

    Science.gov (United States)

    Stefanidis, Aneta; Verty, Aaron N A; Allen, Andrew M; Owens, Neil C; Cowley, Michael A; Oldfield, Brian J

    2009-01-01

    The administration of antipsychotic drugs to human patients or experimental animals leads to significant weight gain, which is widely presumed to be driven by hyperphagia; however, the contribution from energy expenditure remains unclear. These studies aim to examine the contribution of shifts in energy expenditure, particularly those involving centrally mediated changes in thermogenesis, to the body weight gain associated with the administration of olanzapine to female Sprague Dawley rats. Olanzapine (6 mg/kg/day orally) caused a transient increase in food intake but a maintained increase in body weight. When pair-fed rats were treated with olanzapine, body weight continued to rise compared to vehicle-treated rats, consistent with a reduction in energy expenditure. Brown adipose tissue (BAT) temperature, measured using biotelemetry devices, decreased immediately after the onset of olanzapine treatment and remained depressed, as did physical activity. UCP1 expression in interscapular BAT was reduced following chronic olanzapine treatment. An acute injection of olanzapine was preceded by an injection of a retrograde tracer into the spinal cord to evaluate the nature of the olanzapine-activated neural pathway. Levels of Fos protein in a number of spinally projecting neurons within discrete hypothalamic and brainstem sites were elevated in olanzapine-treated rats. Some of these neurons in the perifornical region of the lateral hypothalamus (LHA) were also Orexin A positive. These data collectively show a significant impact of thermogenesis (and physical activity) on the weight gain associated with olanzapine treatment. The anatomical studies provide an insight into the central neuroanatomical substrate that may subserve the altered thermogenic responses brought about by olanzapine.

  11. Isolation-drug resistance profile and molecular characterization of indigenous typical and atypical mycobacteria.

    Science.gov (United States)

    Khanum, Tanveer; Rasool, Sheikh Ajaz; Ajaz, Munazza; Khan, Asif Iqbal

    2011-10-01

    One hundred and fifty mycobacterial isolates from different pathological Labs. of Karachi were collected and screened as acid fast. On the bases of phenotypic and biochemical results, it was found that, 58.66% isolates were typical mycobacteria while 41.33% belonged to atypical mycobacteria. The individual percentages of different mycobacterial species include: M. xenopi 35%, M. thermoresistible 19 %, M. terrae complex 6 %, M. marinum 6 %, M. fortuitum 6 %, M. kansasii 25 % and M. tuberculosis 58.66 %. The sensitivity of mycobacterial isolates was determined against 5 first line, 3 second line and 1 third line anti-tuberculosis drugs. The highest number of the isolates (typical and atypical mycobacteria) offered resistance against isoniazid and streptomycin. Clarithromycin was found to be the drug of choice as regards the drug sensitivity in case of atypical mycobacterial isolates. A total of 40 isolates were subjected to PCR based identification and differentiation of 16S rRNA gene(s). Accordingly, 37.5% isolates were identified as typical mycobacteria while 25% were identified as atypical mycobacteria. These findings carry significance because a detailed research based identification (PCR and Multiplex PCR based) regarding indigenous mycobacteria has been reported for the first time in Pakistan. However, both the approaches (conventional and molecular methods) have experimental importance while identifying these organisms.

  12. Covariation between motor signs and negative symptoms in drug-naive subjects with schizophrenia-spectrum disorders before and after antipsychotic treatment.

    Science.gov (United States)

    Peralta, Victor; de Jalón, Elena García; Campos, María S; Cuesta, Manuel J

    2017-08-29

    Objective To examine the covariation between negative symptoms and motor signs in a broad sample of drug-naïve subjects with schizophrenia-spectrum psychoses before and after inception of antipsychotic medication. One-hundred and eighty-nine antipsychotic-naïve subjects with DSM-IV schizophrenia-spectrum psychoses were assessed for negative symptoms including affective flattening, alogia, avolition/apathy and anhedonia/associality, and motor signs including catatonia, parkinsonism and dyskinesia. We examined the association between negative and motor features at baseline, 4-weeks after inception of antipsychotic treatment and that of their mean change over the treatment period, such as their trajectories and treatment response pattern. At the drug-naïve state, motor signs were strongly related to affective flattening and alogia (p0.01). Although to a different extent, motor and negative features showed drug-responsive, drug-worsening, of drug-unchanged patterns of response to antipsychotic medication. The main predictors of negative and motor features in treated subjects were their corresponding baseline ratings (p<0.001). Negative and motor features are differentiated, but to some extent, overlapping domains that are meaningfully influenced by antipsychotic medication. At the drug-naïve state, motor signs and the diminished expression domain of negative symptoms may share underlying neurobiological mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe

    2017-01-01

    A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she...... negative. The low level of quetiapine in the hair segment and its absence in the other segments indicate that the victim had only consumed one or a few doses of quetiapine within that period and was not a regular user. This study describes the first drug-facilitated assault involving a single dose...

  14. 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 (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.

  15. Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment

    DEFF Research Database (Denmark)

    Sjo, Christina Power; Stenstrøm, Anne Dorte; Bojesen, Anders Bo

    2017-01-01

    OBJECTIVES: Mental illness is often accompanied by poor physical health and shorter life expectancy. Second-generation antipsychotics (SGAs) are suspected of increasing cardiovascular risk, possibly through development of metabolic syndrome (MetS), and the risk of adverse outcome is even higher...... if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG...

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

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    Stefanović Vesna

    2015-01-01

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

  17. Antipsychotic polypharmacy.

    Science.gov (United States)

    Ananth, J; Parameswaran, S; Gunatilake, S

    2004-01-01

    The administration of more than one drug for a single medical condition is considered to be polypharmacy. There are many possible reasons for polypharmacy: (1) psychosis is a chronic disease that cannot be cured; (2) expectations to improve patients' quality of life beyond what drugs can actually do is high; (3) the lack of side effects and interactions can cause physicians to be more daring in terms of potential complications; (4) information from the Internet may cause patients and their families to demand medications; (5) the diluted mental health system allows legal guardians and other mental health professionals to force physicians to provide multiple drugs; (6) many new drugs are available; and (7) physicians are forced to shorten hospitalization days. The 1997 American Psychiatric Association Practice Research Network found that 17% of 146 patients with schizophrenia were treated concurrently with more than one antipsychotic medication. Polypharmacy may increase the risk of adverse effects, drug interactions, noncompliance, and medication errors. It is not wise to use polypharmacy only to prevent side effects and drug and interactions. Our attempts to reduce polypharmacy may fail, as academicians also propagate polypharmacy, and all of the algorithms indicate polypharmacy as an option, putting physicians in a legal and ethical bind. Techniques such as experimental ward, peer review, computer information feedback, and comparing different techniques may temporarily reduce polypharmacy but long-term outcome is not affected. Scientific data on the efficacy of polypharmacy is needed in order to sort out good and bad polypharmacy.

  18. Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS. PMID:25116424

  19. The ticking of the epigenetic clock: antipsychotic drugs in old age

    Directory of Open Access Journals (Sweden)

    Adonis Sfera

    2016-08-01

    Full Text Available AbstractBackground: Exposed to antipsychotic drugs (APDs, older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE, including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs, however they seldom progresses to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear.CNS small vessel disease (SVD is a well-known age-related risk factor for strokes, dementia and sudden death, which may constitute the initial CVAE-predisposing pathology. We therefore propose a two strike CVAE paradigm in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities (WMH may be directly proportional with the CVAE risk.To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4. Since microRNA-29 has shown efficacy against the same malignancies, and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 up-regulation, which in turn facilitates the development of SVD. Aim: to assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.Method: we conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity, and may be relevant for CVAE

  20. Off-label utilization of antipsychotics

    African Journals Online (AJOL)

    Adele

    was used to determine factors predicting the prescription of atypical antipsychotics and the prescription of benzodiazepines. The forward stepwise method using likelihood-ratio statistic was performed. The third model, predicting the antipsychotic dose range used was analysed by stepwise multinominal logistic regression.

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

    African Journals Online (AJOL)

    Off-label utilization of antipsychotics. DF Zullino, R Bilancioni, P Conus, B Schwartz, Y Khazaal, P Baumann. Abstract. 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 ...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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......The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We...... 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...

  3. Social cognition and visual perception in schizophrenia inpatients treated with first-and second-generation antipsychotic drugs.

    Science.gov (United States)

    Kucharska-Pietura, Katarzyna; Mortimer, Ann; Tylec, Aneta; Czernikiewicz, Andrzej

    2012-04-01

    Social cognition captures affect recognition, social cue perception, "theory of mind," empathy, and attributional style. The aim of our study was to assess social cognition in schizophrenia inpatients being treated with first-generation antipsychotic drugs (FGAs), n=28 (perphenazine and haloperidol, FGAs) or with second-generation antipsychotic drugs (SGAs), n=56 (olanzapine and clozapine, SGAs). Eighty-four patients completed the Facial Expression Recognition Test, the Voice Emotion Recognition Test, the Short Recognition Memory Test for Faces, and the Reading the Mind in the Eyes Test. Patients also completed the Visual Object and Space Perception Test (VOSP) as a control task, which would not engage social cognition. The patients were compared with fifty healthy controls matched for age and gender. There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups. Nor was olanzapine superior to clozapine, FGAs or both. However, patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs, a 10% difference. We cannot conclude that SGAs were associated with better social cognition than FGAs. However, there were small but significant advantages for SGAs in non-social visual processing function, as evaluated with the VOSP.

  4. Antipsychotic drug effects on left prefrontal phospholipid metabolism: a follow-up 31P-2D-CSI study of haloperidol and risperidone in acutely ill chronic schizophrenia patients.

    Science.gov (United States)

    Smesny, Stefan; Langbein, Kerstin; Rzanny, Reinhardt; Gussew, Alexander; Burmeister, Hartmut P; Reichenbach, Juergen R; Sauer, Heinrich

    2012-07-01

    ³¹Phosphorous magnetic resonance spectroscopy (2D chemical shift imaging, CSI) allows multiregional study of membrane phospholipids and high-energy phosphates in vivo. Increased membrane lipid turnover and impaired energy supply have repeatedly been shown in first-episode schizophrenia patients, and might be a target of drug actions other than dopamine receptors. Here, we explored differential metabolic effects of a typical vs. an atypical antipsychotic on brain phospholipids. We applied 2D-CSI MR spectroscopy in 17 recurrent-episode schizophrenia patients off antipsychotics at baseline and at follow-up after 6 weeks, during which 7 patients were treated with haloperidol (10-16 mg/d) and 10 with risperidone (4-6 mg/d). Psychopathology changes were assessed using PANSS, BPRS and CGI scores. Follow-up analysis using repeated measure ANOVA revealed different effects of both antipsychotic agents: while risperidone generally increased metabolite levels, haloperidol showed a tendency to decrease them. This diverging effect was significant for ATP levels in the left lateral frontal cortex. Furthermore, risperidone increased ATP in the left dorsolateral prefrontal cortex, left anterior temporal cortex and left insular cortex, basal ganglia, and anterior cerebellum, along with left frontal and prefrontal increase of PCr, PDE and PME in these brain regions. Risperidone seems to stimulate neuronal and synaptic phospholipid remodeling in left frontal and prefrontal regions, and to a lesser extent also in temporal and insular cortices. We discuss these effects with respect to clinical effects on negative and cognitive symptoms, as well as interaction of phospholipid metabolism with glutamatergic neurotransmission. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Japan useful medication program for schizophrenia (JUMPs)-long-term study on discontinuation rate, resolution and remission, and improvement in social functioning rate associated with atypical antipsychotic medications in patients with schizophrenia

    Science.gov (United States)

    2013-01-01

    Background It is desirable to establish evidence for the selection of antipsychotics from the viewpoint of recovery of social activity in individual patient with schizophrenia receiving medication. From this perspective, awareness of the importance of studies about drug effectiveness on treatment discontinuation rate, remission rate, and improvement in QOL has grown recently. In Western countries, numerous reports are available in effectiveness studies, which are related to olanzapine and risperidone primarily, whereas evidence for other second-generation antipsychotics (SGAs) is poor. In Japan, no effectiveness study has been reported: thus, it is desirable to collect data that will serve as evidence for selection of the 3 SGAs approved after olanzapine. Methods The present study was a long-term effectiveness study under healthcare setting in Japan. It was designed as an open-label, multicenter, randomized, comparative study involving 104-week oral treatment with 1 of the 3 drugs (aripiprazole, blonanserin, and paliperidone) in patients with schizophrenia aged 20 years or over who required antipsychotic medication or switching of the current medication to others for reasons such as lack of efficacy and intolerability. The primary endpoint is treatment discontinuation rate for any causes. The secondary endpoints include remission rate, improvement of social activity, alleviation, aggravation or recurrence of psychiatric symptoms, and safety. The target number of subjects was set at 300. Discussion Because this study is expected to yield evidence regarding the selection of antipsychotics for facilitating the recovery of social activity in patients with schizophrenia, it is considered highly valuable to perform this effectiveness study under ordinary healthcare setting in Japan. Trial registration UMIN Clinical Trials Registry 000007942 PMID:24090047

  6. Efficacy of Atypical Antipsychotics in the Management of Acute Agitation and Aggression in Hospitalized Patients with Schizophrenia or Bipolar Disorder: Results from a Systematic Review

    OpenAIRE

    Correll, Christoph U.; ,; Kane, John M.; Masand, Prakash

    2016-01-01

    Summary Acute agitation and aggression are common symptoms in patients with bipolar disorder and schizophrenia. In this review, we discuss the prevalence, clinical assessment strategies, treatment options, and current Western and Chinese guidelines for the management of acute agitation and aggression in patients with bipolar disorder or schizophrenia. Among available approaches, we discuss in detail recent evidence supporting the use of intramuscular (IM) antipsychotics and some recently appr...

  7. Adverse events and treatment failure leading to discontinuation of recently approved antipsychotic drugs in schizophrenia: A network meta-analysis.

    Science.gov (United States)

    Tonin, Fernanda S; Piazza, Thais; Wiens, Astrid; Fernandez-Llimos, Fernando; Pontarolo, Roberto

    2015-12-01

    Objective:We aimed to gather evidence of the discontinuation rates owing to adverse events or treatment failure for four recently approved antipsychotics (asenapine, blonanserin, iloperidone, and lurasidone).Methods: A systematic review followed by pairwise meta-analysis and mixed treatment comparison meta analysis(MTC) was performed, including randomized controlled trials (RCTs) that compared the use of the above-mentioned drugs versus placebo in patients with schizophrenia. An electronic search was conducted in PubMed, Scopus, Science Direct, Scielo, the Cochrane Library, and International Pharmaceutical Abstracts(January 2015). The included trials were at least single blinded. The main outcome measures extracted were discontinuation owing to adverse events and discontinuation owing to treatment failure.Results: Fifteen RCTs were identified (n = 5400 participants) and 13 of them were amenable for use in our meta-analyses. No significant differences were observed between any of the four drugs and placebo as regards discontinuation owing to adverse events, whether in pairwise meta-analysis or in MTC. All drugs presented a better profile than placebo on discontinuation owing to treatment failure, both in pairwise meta-analysis and MTC. Asenapine was found to be the best therapy in terms of tolerability owing to failure,while lurasidone was the worst treatment in terms of adverse events. The evidence around blonanserin is weak.Conclusion: MTCs allowed the creation of two different rank orders of these four antipsychotic drugs in two outcome measures. This evidence-generating method allows direct and indirect comparisons, supporting approval and pricing decisions when lacking sufficient, direct, head-to-head trials.

  8. tional antipsychotic in South Africa

    African Journals Online (AJOL)

    Enrique

    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 ...

  9. Antipsychotic drugs up-regulate tryptophan hydroxylase in ADF neurons of Caenorhabditis elegans: role of calcium-calmodulin-dependent protein kinase II and transient receptor potential vanilloid channel.

    Science.gov (United States)

    Donohoe, Dallas R; Phan, Thang; Weeks, Kathrine; Aamodt, Eric J; Dwyer, Donard S

    2008-08-15

    Antipsychotic drugs produce acute behavioral effects through antagonism of dopamine and serotonin receptors, and long-term adaptive responses that are not well understood. The goal of the study presented here was to use Caenorhabditis elegans to investigate the molecular mechanism or mechanisms that contribute to adaptive responses produced by antipsychotic drugs. First-generation antipsychotics, trifluoperazine and fluphenazine, and second-generation drugs, clozapine and olanzapine, increased the expression of tryptophan hydroxylase-1::green fluorescent protein (TPH-1::GFP) and serotonin in the ADF neurons of C. elegans. This response was absent or diminished in mutant strains lacking the transient receptor potential vanilloid channel (TRPV; osm-9) or calcium/calmodulin-dependent protein kinase II (CaMKII; unc-43). The role of calcium signaling was further implicated by the finding that a selective antagonist of calmodulin and a calcineurin inhibitor also enhanced TPH-1::GFP expression. The ADF neurons modulate foraging behavior (turns/reversals off food) through serotonin production. We found that short-term exposure to the antipsychotic drugs altered the frequency of turns/reversals off food. This response was mediated through dopamine and serotonin receptors and was abolished in serotonin-deficient mutants (tph-1) and strains lacking the SER-1 and MOD-1 serotonin receptors. Consistent with the increase in serotonin in the ADF neurons induced by the drugs, drug withdrawal after 24-hr treatment was accompanied by a rebound in the number of turns/reversals, which demonstrates behavioral adaptation in serotonergic systems. Characterization of the cellular, molecular, and behavioral adaptations to continuous exposure to antipsychotic drugs may provide insight into the long-term clinical effects of these medications.

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

    Directory of Open Access Journals (Sweden)

    Jui-Hsiu Tsai

    2005-12-01

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

  11. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    Directory of Open Access Journals (Sweden)

    Quevedo-Florez Leonardo

    2017-01-01

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

  12. The explanatory role of stroke as a mediator of the mortality risk difference between older adults who initiate first- versus second-generation antipsychotic drugs.

    Science.gov (United States)

    Jackson, John W; VanderWeele, Tyler J; Viswanathan, Anand; Blacker, Deborah; Schneeweiss, Sebastian

    2014-10-15

    Antipsychotic drugs are used to treat dementia-related symptoms in older adults, and observational studies show higher risks of death and stroke associated with the use of first-generation antipsychotic drugs (FGAs) compared with second-generation antipsychotic drugs (SGAs). However, the extent to which stroke explains the differential mortality risk between FGA use and SGA use in older adults is unclear. We followed those who initiated use of antipsychotic drugs (9,777 FGA users and 21,164 SGA users) aged 65 years or older, and who were enrolled in Medicare and either the New Jersey or Pennsylvania pharmacy assistance program during 1994 to 2005, over 180 days for the outcomes of stroke and death. We estimated direct and indirect effects by comparing 180-day mortality risks associated with the use of FGAs versus SGAs as mediated by stroke on the risk ratio scale, as well as the proportion mediated on the risk difference scale. FGA use was associated with marginally higher risks of stroke (risk ratio =1.24, 95% confidence interval (CI): 1.01, 1.53) and death (risk ratio = 1.15, 95% CI: 1.08, 1.22) compared with SGA use, but stroke explained little (2.7%) of the observed difference in mortality risk. The indirect effect was null (risk ratio = 1.004, 95% CI: 1.000, 1.008), and the direct effect was equal to the total effect of antipsychotic drug type (FGA vs. SGA) on mortality risk (risk ratio = 1.15, 95% CI: 1.08, 1.22). These results suggest that the difference in mortality risk between users of FGAs and SGAs may develop mostly through pathways that do not involve stroke. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Using antipsychotic agents in older patients.

    Science.gov (United States)

    Alexopoulos, George S; Streim, Joel; Carpenter, Daniel; Docherty, John P

    2004-01-01

    absence of a major psychiatric syndrome. However, antipsychotics were favored in several other disorders. For agitated dementia with delusions, the experts' first-line recommendation is an antipsychotic drug alone; they would also consider adding a mood stabilizer. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. There was no first-line recommendation for agitated dementia without delusions; an antipsychotic alone was high second line (rated first line by 60% of the experts). The experts'first-line recommendation for late-life schizophrenia was risperidone (1.25-3.5 mg/day). Quetiapine (100-300 mg/day), olanzapine (7.5-15 mg/day), and aripiprazole (15-30 mg/day) were high second line. For older patients with delusional disorder, an antipsychotic was the only treatment recommended. For agitated nonpsychotic major depression in an older patient, the experts' first-line recommendation was an antidepressant alone (77% first line); second-line options were an antidepressant plus an antipsychotic, electroconvulsive therapy (ECT), an antidepressant plus a benzodiazepine, and an antidepressant plus a mood stabilizer. For nonpsychotic major depression with severe anxiety, the experts recommended an antidepressant alone (79% first line) and would also consider adding a benzodiazepine or mood stabilizer to the antidepressant. If an older patient with adequate dosages for adequate duration, there was limited support for adding an atypical antipsychotic to the antidepressant (36% first line after two failed antidepressant trials). Treatment of choice for geriatric psychotic major depression was an antipsychotic plus an antidepressant (98% first line), with ECT another first-line option (71% first line). For mild geriatric nonpsychotic mania, the first-line recommendation is a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving

  14. Effect of second-generation antipsychotics on caregiver burden in Alzheimer's disease.

    Science.gov (United States)

    Mohamed, Somaia; Rosenheck, Robert; Lyketsos, Constantine G; Kaczynski, Richard; Sultzer, David L; Schneider, Lon S

    2012-01-01

    Alzheimer's disease (AD) imposes a severe burden upon patients and their caregivers. Severity of psychiatric symptoms and behavioral disturbances is an important determinant of caregivers' experience of burden. These symptoms may be improved with atypical antipsychotic treatment. Data from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) trial were used to evaluate the effect of atypical antipsychotics versus placebo on the experiences of caregivers of outpatients with AD. We compared the effect of atypical antipsychotic drugs (olanzapine, risperidone, or quetiapine-considered together as a group) versus placebo on the experiences of caregivers of AD outpatients (diagnosed according to DSM-IV-TR). We also evaluated whether improvement in patients' psychiatric and behavioral symptoms mediated the relationship between drug treatment and caregiver burden. The CATIE-AD trial, conducted from April 2001 through November 2004, included outpatients (mean age = 77.9 years [SD = 7.5 years]) in usual care settings and assessed treatment effectiveness over a 9-month period at 42 US sites. In a set of secondary analyses, data from CATIE-AD participants who had at least 1 postbaseline outcome assessment and data from their caregivers were examined in an intention-to-treat (ITT) analysis (N = 361). A phase 1-only analysis was conducted including only observations while patients were receiving the initially randomized drug (N = 153). The Burden Interview, the Beck Depression Inventory, and the Neuropsychiatric Inventory (NPI) Caregiver Distress Scale were used to evaluate caregiver burden. In both ITT and phase 1-only analyses, caregivers of patients treated with second-generation antipsychotics scored significantly lower than caregivers of patients receiving placebo on both the Burden Interview (P = .0090) and the NPI Caregiver Distress Scale (P = .0209). These differences appeared to have been mediated by lower levels of agitation

  15. Efficacy and acceptability of atypical antipsychotics for the treatment of post-traumatic stress disorder: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

    Science.gov (United States)

    Liu, Xiao-hui; Xie, Xin-hui; Wang, Ke-yong; Cui, Hong

    2014-11-30

    As some evidences demonstrated that atypical antipsychotics (AA) may be efficacious in treating post-traumatic stress disorder (PTSD), we preformed a meta-analysis of randomized, double-blind, placebo-controlled clinical trials (RCTs) of AAs for the treatment of PTSD. Two hundred and fifty one papers were searched and screened. Eight RCTs met the inclusion criteria. AAs may be superior to placebo in the treatment of PTSD, as indicated by the changes in Clinician Administered PTSD Scale (CAPS) total scores (weighted mean differences (WMD)=-5.89, 95% confidence interval (CI) [-9.21, -2.56], P=0.0005) and also in CAPS subscale intrusion (WMD=-2.58, 95% CI[-3.83, -1.33], Pdifference (OR=1.24, 95%CI [0.78, 1.97], P=0.36). PTSD symptom cluster, especially in intrusion and hyperarousal. However, we should be careful to generalize the conclusion because of the small number of included trails. We expect more RCTs will be done in the future so as to clarify the specific value of AAs for PTSD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-10-01

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

  17. Antipsychotic drug exposure and risk of pneumonia: a systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Nosè, Michela; Recla, Elisabetta; Trifirò, Gianluca; Barbui, Corrado

    2015-08-01

    Pneumonia is one of the major leading causes of morbidity and mortality among persons aged 65 years or older. Recently, several studies suggested an association between antipsychotic (AP) use and risk of pneumonia in elderly patients. The aim of the present systematic review and meta-analysis of observational studies was to investigate if first-generation and second-generation AP drugs increase the risk of pneumonia in the elderly and also in the younger population, and to ascertain the risk associated with exposure to individual drugs. All observational cohort or case-control studies that reported data on pneumonia outcomes in individuals exposed to AP drugs as compared with individuals unexposed or with past exposure to AP drugs were included in the systematic review and meta-analysis. Study participants were of either sex and of any age with no restrictions in terms of diagnostic categories. The risk of pneumonia was significantly increased by exposure to first-generation AP drugs (odds ratio (OR) 1.68, 95% confidence interval (95%CI) 1.39-2.04, I(2)  = 47%) and exposure to second-generation AP drugs (OR 1.98, 95%CI 1.67-2.35, I(2)  = 36.7%). The risk was similar among different diagnostic categories and age groups, in elderly and young-adult populations; the finding on age was corroborated by a meta-regression analysis, which did not detect any relationship between age and risk of pneumonia. Only few studies provided data on individual drugs. Systematic review of current observational evidence suggests that exposure to first-generation and second-generation AP drugs is associated with an increased risk of pneumonia. The present systematic review expands previous knowledge by showing that the increased risk not only applies to elderly individuals but also to younger patients. The information about the risk of pneumonia for individual compounds is still very limited. Copyright © 2015 John Wiley & Sons, Ltd.

  18. The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs

    OpenAIRE

    Chouinard, Guy

    2006-01-01

    Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, ...

  19. Do Restrictions on Antipsychotic Use Differ Between Medicare Part D Stand-Alone Versus Medicare Advantage Plans?

    Science.gov (United States)

    Chou, Joshua; Brandt, Nicole J; Loh, F Ellen; Stuart, Bruce

    2017-02-01

    The objective of this study was to describe the type of restrictions and differences among antipsychotic users enrolled in Medicare Part D Stand-Alone (PDPs) and Advantage (MAPDs) prescription drug plans. This retrospective study used data from Chronic Condition Data Warehouse, comprising a random 5% sample of the Medicare population in 2008. This study used bivariate analyses and multivariate logistical regression models to study differences in formulary restrictions on antipsychotic use between PDP and MAPD enrollees, adjusting for enrollee characteristics. Dependent variables included type of restriction and antipsychotic therapeutic class. The study sample was restricted to continuous Part D enrollees (N = 1,346,978) stratified by plan type, MAPDs (N = 435,591), and PDPs (N = 911,387). According to the bivariate analysis, antipsychotic users enrolled in PDPs were more likely to encounter restrictions (39.8%), compared with those in MAPDs (30.3%). In the multivariate analyses, antipsychotic users in MAPDs were less likely to face any restriction (odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.72-0.78). Furthermore, atypical antipsychotic users in MAPDs were less likely to face any restriction (OR = 0.76, 95% CI 0.73-0.79), while first-generation antipsychotic users in MAPDs were more likely to face any restriction (OR = 1.87, 95% CI 1.32-2.65). Low-income subsidy (LIS) beneficiaries using any antipsychotic were much more likely to face restrictions compared with non-LIS beneficiaries. PDP enrollees prescribed antipsychotics were more likely to face formulary restrictions, as opposed to those in MAPDs. LIS beneficiaries enrolled in PDPs faced much higher risk of restricted access to this "protected" drug class.

  20. Some novelties and recommendations by swithing antipsychotics

    Directory of Open Access Journals (Sweden)

    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.

  1. Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials

    Directory of Open Access Journals (Sweden)

    Michele Fornaro

    2016-02-01

    Full Text Available Evidence supporting the use of second generation antipsychotics (SGAs in the treatment of acute depression with mixed features (MFs associated with bipolar disorder (BD is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo- controlled trials (RCTs or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI. Six RCTs and one open-label placebo-controlled studies (including post-hoc reports representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS (SMD −0.74, 95% CI −1.20 to −0.28, n SGA = 907, control = 652. Meta-analysis demonstrated that participants in receipt of SGA (n = 979 experienced a large improvement in the Montgomery–Åsberg Depression Rating Scale (MADRS scores (SMD −1.08, 95% CI −1.35 to −0.81, p < 0.001 vs. placebo (n = 678. Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable

  2. Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy

    Directory of Open Access Journals (Sweden)

    Stanković Žana

    2013-01-01

    Full Text Available Background/Aim. There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. Methods. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20 (ICD-10, 1992 clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19 were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation and the patients from the oral group (n = 37 were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale] and attitudes toward medication [Drug Attitude Inventory (DAI subscale] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's χ2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Results. Significant betweengroup differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found

  3. Blonanserin, a novel antipsychotic, is suitable for treating schizophrenia associated with hyperprolactinemia: a case series.

    Science.gov (United States)

    Kawabe, Kentaro; Horiuchi, Fumie; Ueno, Shu-ichi

    2013-01-01

    Recently, atypical antipsychotic agents have primarily been used in pharmacological treatment of schizophrenia because of the fewer associated adverse effects. Blonanserin is a novel atypical antipsychotic recently introduced to treat patients with schizophrenia in Japan and South Korea. In this study, we examined the efficacy of switching antipsychotic medications to blonanserin monotherapy in patients with chronic schizophrenia with associated hyperprolactinemia. Ten schizophrenic patients (5 males and 5 females) with hyperprolactinemia were recruited. Clinical data before (baseline) and 12 weeks after (end point) switching to blonanserin monotherapy were assessed using the Brief Psychiatric Rating Scale score, Drug-Induced Extrapyramidal Symptoms Scale, and serum prolactin levels. The mean (SD) blonanserin dosage was 14.8 (3.8) mg/d. After switching to blonanserin, there were significant improvements in the Brief Psychiatric Rating Scale in the patients from both sexes. Moreover, serum prolactin levels in the female patients significantly decreased to within reference range. There were no additional adverse effects observed with the blonanserin treatment. Switching to blonanserin can reverse medication-induced prolactin elevations found in female patients- and blonanserin is a suitable antipsychotic for schizophrenic patients.

  4. The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs.

    Science.gov (United States)

    Chouinard, Guy

    2006-05-01

    Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, such as in panic disorder and mania, were found with the introduction of 2 high-potency benzodiazepines, clonazepam and alprazolam, which were thought to have serotonergic properties. Our initial clinical trials of fluoxetine and sertraline led to their approved indications in the treatment of obsessive-compulsive disorder, and our trials of gabapentin led to new indications in anxiety disorders (generalized anxiety, panic attack and social phobia) and sleep disorders (insomnia).

  5. Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

    OpenAIRE

    Pacher, Pal; Kecskemeti, Valeria

    2004-01-01

    The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na+, Ca2+ and K+ channels often leading to life-threatening arrhythmia.

  6. Differences in Antipsychotic-Related Adverse Events in Adult, Pediatric, and Geriatric Populations.

    Science.gov (United States)

    Sagreiya, Hersh; Chen, Yi-Ren; Kumarasamy, Narmadan A; Ponnusamy, Karthik; Chen, Doris; Das, Amar K

    2017-02-26

    In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved based on clinical trials in adult patients only. Preliminary studies have shown that the "off-label" use of these drugs in pediatric and geriatric populations may result in adverse events not found in adults. In this study, we utilized the large-scale U.S. Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) database to look at differences in adverse events from antipsychotics among adult, pediatric, and geriatric populations. We performed a systematic analysis of the FDA AERS database using MySQL by standardizing the database using structured terminologies and ontologies. We compared adverse event profiles of atypical versus typical antipsychotic medications among adult (18-65), pediatric (age 65) populations. We found statistically significant differences between the number of adverse events in the pediatric versus adult populations with aripiprazole, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and thiothixene, and between the geriatric versus adult populations with aripiprazole, chlorpromazine, clozapine, fluphenazine, haloperidol, paliperidone, promazine, risperidone, thiothixene, and ziprasidone (p < 0.05, with adjustment for multiple comparisons). Furthermore, the particular types of adverse events reported also varied significantly between each population for aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (Chi-square, p < 10-6). Diabetes was the most commonly reported side effect in the adult population, compared to behavioral problems in the pediatric population and neurologic symptoms in the geriatric population. We also found discrepancies between the frequencies of reports in AERS and in the literature. Our analysis of the FDA AERS database shows that there are significant differences in both

  7. Do depressed patients on adjunctive atypical antipsychotics demonstrate a better quality of life compared to those on antidepressants only? A comparative cross-sectional study of a nationally representative sample of the US population.

    Science.gov (United States)

    Al-Ruthia, Yazed Sulaiman; Hong, Song Hee; Solomon, David

    2015-01-01

    The adjunctive use of some atypical antipsychotics (AAPs) has been popular for patients with treatment-resistant depression. However, little is known about the impact of these agents on patients' Health-related quality of life (HRQoL). The objective of this study is to examine the impact of the adjunctive AAPs use on HRQoL among users of antidepressants with self-reported depression. Patients with depression (ICD-9-CM: 296, 300, and 311), and to have used the given AAPs and/or antidepressants for at least a year, were identified in the Medical Expenditure Panel Survey of 2008-2011. The patients were classified into users of adjunctive AAPs (i.e., antidepressants plus AAPs) and users of antidepressants only. Adjusted multivariate linear regression analyses were conducted to examine the association between the utilization of AAPs and HRQoL measure.(c) A total of 3638 participants who met the inclusion criteria were identified (306 on AAPs vs. 3332 on antidepressants only). The study subjects were ≥18 years, predominately White (91.9%) and female (71%). The AAPs utilization was not associated with higher scores in the Physical Component Summary (PCS-12) of the Short Form Health Survey (SF-12v2) (β = 1.542, 95% CI = -0.0142 to 3.0977, P = 0.0521). Rather, it was negatively associated with the Mental Component Summary (MCS-12) scores of the SF-12v2 (β = -1.5537, 95% CI = -3.0247 to -0.0827, P = 0.0385). The utilization of AAPs was not associated with higher scores of HRQoL. The findings of this study should underscore the need to consider other treatment options as add-on therapy for depression before resorting to AAPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Identification of antipsychotic drug fluspirilene as a potential p53-MDM2 inhibitor: a combined computational and experimental study

    Science.gov (United States)

    Patil, Sachin P.; Pacitti, Michael F.; Gilroy, Kevin S.; Ruggiero, John C.; Griffin, Jonathan D.; Butera, Joseph J.; Notarfrancesco, Joseph M.; Tran, Shawn; Stoddart, John W.

    2015-02-01

    The inhibition of tumor suppressor p53 protein due to its direct interaction with oncogenic murine double minute 2 (MDM2) protein, plays a central role in almost 50 % of all human tumor cells. Therefore, pharmacological inhibition of the p53-binding pocket on MDM2, leading to p53 activation, presents an important therapeutic target against these cancers expressing wild-type p53. In this context, the present study utilized an integrated virtual and experimental screening approach to screen a database of approved drugs for potential p53-MDM2 interaction inhibitors. Specifically, using an ensemble rigid-receptor docking approach with four MDM2 protein crystal structures, six drug molecules were identified as possible p53-MDM2 inhibitors. These drug molecules were then subjected to further molecular modeling investigation through flexible-receptor docking followed by Prime/MM-GBSA binding energy analysis. These studies identified fluspirilene, an approved antipsychotic drug, as a top hit with MDM2 binding mode and energy similar to that of a native MDM2 crystal ligand. The molecular dynamics simulations suggested stable binding of fluspirilene to the p53-binding pocket on MDM2 protein. The experimental testing of fluspirilene showed significant growth inhibition of human colon tumor cells in a p53-dependent manner. Fluspirilene also inhibited growth of several other human tumor cell lines in the NCI60 cell line panel. Taken together, these computational and experimental data suggest a potentially novel role of fluspirilene in inhibiting the p53-MDM2 interaction. It is noteworthy here that fluspirilene has a long history of safe human use, thus presenting immediate clinical potential as a cancer therapeutic. Furthermore, fluspirilene could also serve as a structurally-novel lead molecule for the development of more potent, small-molecule p53-MDM2 inhibitors against several types of cancer. Importantly, the combined computational and experimental screening protocol

  9. Medication and participation: A qualitative study of patient experiences with antipsychotic drugs.

    Science.gov (United States)

    Lorem, Geir F; Frafjord, Jartrud S; Steffensen, Marie; Wang, Catharina E A

    2014-05-01

    Patient autonomy is recognised within mental healthcare, although the capacity to participate in one's own treatment planning is often reduced during a psychotic crisis. The patient may not be sufficiently competent to give consent or express preferences at the time treatment decisions are made. Nine participants were interviewed shortly after a crisis. We discussed participation in the treatment planning and recovery process with particular emphasis on interactions with professionals and understanding treatment. The participants recognised the need for drugs and mental healthcare but emphasised the need for better cooperation and communication. To facilitate the development of patient autonomy, we recommend an increased emphasis on providing information and participating in a dialogue about drug treatment options. This could counteract many of the negative experiences reported. The use of debriefing during hospitalisation and following coercion can be a practical tool for clarifying patient preferences and mutual understanding.

  10. Infant safety with antipsychotic therapy in breast-feeding: a systematic review.

    Science.gov (United States)

    Gentile, Salvatore

    2008-04-01

    A relatively high number of women may suffer from psychotic symptoms at postpartum onset. Such symptoms may have devastating effects not only on the mothers but also on the later infant's well being. Children born to mothers with psychosis are at increased risk of physiologic, psychological, and personality development disturbance, whereas children born to mothers with bipolar disorder are at increased risk of early-onset psychiatric disorders. Hence, clinicians should consider it imperative to prevent or manage effectively psychotic and affective relapses in new mothers. To analyze the literature for information about the safety of first- and second-generation antipsychotics for breast-fed infants in order to individuate the safest treatment option for women who need such medications during puerperium. A computerized search was carried out on MEDLINE/PubMed/TOXNET (1950-January 2008). The following key words were used: breast-feeding, lactation, puerperium, psychotropic drugs, atypical antipsychotics, typical antipsychotics, and neuroleptics. No conclusions can be drawn about the risk/benefit profile of the majority of antipsychotic medications in breast-feeding. Hence, when clinicians are forced to start antipsychotic treatment in drug-naive patients, the choice of the safest option should be based on the general effectiveness profile of each agent, with 2 possible exceptions: clozapine (the drug should be considered contraindicated during breast-feeding because of its liability of inducing potential life-threatening events in the infant), and olanzapine (the drug seems to be associated with an increased risk of inducing extrapyramidal reactions in the breast-fed babies). Conversely, in patients who need to continue antipsychotic therapy during breast-feeding, it is suitable to maintain the previous pharmacologic regimen, if known as effective.

  11. Combining the Antipsychotic Drug Haloperidol and Environmental Enrichment after Traumatic Brain Injury Is a Double-Edged Sword.

    Science.gov (United States)

    Folweiler, Kaitlin A; Bondi, Corina O; Ogunsanya, Elizabeth A; LaPorte, Megan J; Leary, Jacob B; Radabaugh, Hannah L; Monaco, Christina M; Kline, Anthony E

    2017-01-15

    Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2.8 mm tissue deformation at 4 m/sec) or sham injury and then were provided HAL (0.5 mg/kg; intraperitoneally [IP]) or vehicle (VEH; 1 mL/kg; IP) commencing 24 h after surgery and once daily for 19 days while housed in EE or standard (STD) conditions. Beam balance/walk and Morris water maze performance were assessed on post-injury days 1-5 and 14-19, respectively, followed immediately by quantification of cortical lesion volumes. The data revealed both expected and unexpected findings. It was not surprising that the TBI groups receiving EE performed significantly better than those in STD housing and that the TBI + STD + HAL group performed worse than the TBI + STD + VEH group (p  0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.

  12. Impact of depression and social support on nonadherence to antipsychotic drugs in persons with schizophrenia in Thailand

    Directory of Open Access Journals (Sweden)

    Sirijit Suttajit

    2010-09-01

    Full Text Available Sirijit Suttajit, Sutrak PilakantaDepartment of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandBackground: Little is known about the effect of social support on nonadherence in persons with schizophrenia, especially in developing Asian countries where social support is considered to be imperative. Additionally, the role of depression as a mediator in the association between social support deficits and nonadherence has not been evaluated.Methods: This was a cross-sectional study conducted in 75 participants at a university hospital in Thailand. Logistic regression was used to determine whether depression and a deficit in social support were associated with nonadherence, and whether depression mediated this association.Results: There were strong relationships between nonadherence and major depressive episodes (odds ratio [OR] 9.5, confidence interval [CI] 2.3–38.9, living alone (OR 21.8, CI 3.5–143.0, and dissatisfaction with support from family (OR 10.0, CI 1.9–53.1. The OR of the association between social support deficits and nonadherence decreased by nearly one half after adjusting for depression.Discussion: Depression and social support deficits were significantly associated with nonadherence in persons with schizophrenia. Depression is important in mediating the association between social support deficits and nonadherence. Enhancing social support, as well as early detection and effective intervention for depression should be emphasized in interventions to improve adherence in persons with schizophrenia.Keywords: nonadherence, schizophrenia, depression, social support, antipsychotic drugs

  13. Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100.

    Science.gov (United States)

    Byun, Nellie E; Grannan, Michael; Bubser, Michael; Barry, Robert L; Thompson, Analisa; Rosanelli, John; Gowrishankar, Raajaram; Kelm, Nathaniel D; Damon, Stephen; Bridges, Thomas M; Melancon, Bruce J; Tarr, James C; Brogan, John T; Avison, Malcolm J; Deutch, Ariel Y; Wess, Jürgen; Wood, Michael R; Lindsley, Craig W; Gore, John C; Conn, P Jeffrey; Jones, Carrie K

    2014-06-01

    Accumulating evidence suggests that selective M4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M4 activators were unsuccessful because of the lack of M4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M4 positive allosteric modulator (PAM) that exerts central effects after systemic administration. We now report that VU0152100 dose-dependently reverses amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M4 KO mice. VU0152100 also blocks amphetamine-induced disruption of the acquisition of contextual fear conditioning and prepulse inhibition of the acoustic startle reflex. These effects were observed at doses that do not produce catalepsy or peripheral adverse effects associated with non-selective mAChR agonists. To further understand the effects of selective potentiation of M4 on region-specific brain activation, VU0152100 alone and in combination with amphetamine were evaluated using pharmacologic magnetic resonance imaging (phMRI). Key neural substrates of M4-mediated modulation of the amphetamine response included the nucleus accumbens (NAS), caudate-putamen (CP), hippocampus, and medial thalamus. Functional connectivity analysis of phMRI data, specifically assessing correlations in activation between regions, revealed several brain networks involved in the M4 modulation of amphetamine-induced brain activation, including the NAS and retrosplenial cortex with motor cortex, hippocampus, and medial thalamus. Using in vivo microdialysis, we found that VU0152100 reversed amphetamine-induced increases in extracellular dopamine levels in NAS and CP. The present data are consistent with an antipsychotic drug-like profile of activity for VU0152100. Taken together, these data support the development of selective M4 PAMs as a new approach to the treatment of psychosis

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

    Directory of Open Access Journals (Sweden)

    Nordon C

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Sofian Berrouiguet

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Long-acting antipsychotic drugs for the treatment of schizophrenia: use in daily practice from naturalistic observations

    Directory of Open Access Journals (Sweden)

    Rossi Giuseppe

    2012-08-01

    Full Text Available Abstract Background Current guidelines suggest specific criteria for oral or long-acting injectable antipsychotic drugs (LAIs. This review aims to describe the demographic and clinical characteristics of the ideal profile of the patient with schizophrenia treated with LAIs, through the analysis of nonrandomized studies. Methods A systematic review of nonrandomized studies in English was performed attempting to analyze the factors related to the choice and use of LAIs in daily practice. The contents were outlined using the Cochrane methods for nonrandomized studies and the variables included demographic as well as clinical characteristics. The available literature did not allow any statistical analysis that could be used to identify the ideal profile of patients with schizophrenia to be treated with LAIs. Results Eighty publications were selected and reviewed. Prevalence of LAI use ranged from 4.8% to 66%. The only demographic characteristics that were consistently assessed through retrieved studies were age (38.5 years in the 1970’s, 35.8 years in the 1980’s, 39.3 years in the 1990’s, to 39.5 years in the 2000’s and gender (male > female. Efficacy was assessed through the use of various symptom scales and other indirect measurements; safety was assessed through extrapyramidal symptoms and the use of anticholinergic drugs, but these data were inconsistent and impossible to pool. Efficacy and safety results reported in the different studies yielded a good therapeutic profile with a maximum of 74% decrease in hospital admissions and the prevalence of extrapyramidal symptoms with LAIs consistently increased at 6, 12, 18, and 24 months (35.4%, 37.1%, 36.9%, and 41.3%, respectively. Conclusions This analysis of the available literature strongly suggests that further observational studies on patients with schizophrenia treated with LAIs are needed to systematically assess their demographic and clinical characteristics and the

  18. Blonanserin extensively occupies rat dopamine D3 receptors at antipsychotic dose range

    Directory of Open Access Journals (Sweden)

    Satoko Baba

    2015-03-01

    Full Text Available Antagonism of the dopamine D3 receptor has been hypothesized to be beneficial for schizophrenia cognitive deficits, negative symptoms and extrapyramidal symptoms. However, recent animal and human studies have shown that most antipsychotics do not occupy D3 receptors in vivo, despite their considerable binding affinity for this receptor in vitro. In the present study, we investigated the D3 receptor binding of blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptors antagonist, in vitro and in vivo. Blonanserin showed the most potent binding affinity for human D3 receptors among the tested atypical antipsychotics (risperidone, olanzapine and aripiprazole. Our GTPγS-binding assay demonstrated that blonanserin acts as a potent full antagonist for human D3 receptors. All test-drugs exhibited antipsychotic-like efficacy in methamphetamine-induced hyperactivity in rats. Treatment with blonanserin at its effective dose blocked the binding of [3H]-(+-PHNO, a D2/D3 receptor radiotracer, both in the D2 receptor-rich region (striatum and the D3 receptor-rich region (cerebellum lobes 9 and 10. On the other hand, the occupancies of other test-drugs for D3 receptors were relatively low. In conclusion, we have shown that blonanserin, but not other tested antipsychotics, extensively occupies D3 receptors in vivo in rats.

  19. Blonanserin extensively occupies rat dopamine D3 receptors at antipsychotic dose range.

    Science.gov (United States)

    Baba, Satoko; Enomoto, Takeshi; Horisawa, Tomoko; Hashimoto, Takashi; Ono, Michiko

    2015-03-01

    Antagonism of the dopamine D3 receptor has been hypothesized to be beneficial for schizophrenia cognitive deficits, negative symptoms and extrapyramidal symptoms. However, recent animal and human studies have shown that most antipsychotics do not occupy D3 receptors in vivo, despite their considerable binding affinity for this receptor in vitro. In the present study, we investigated the D3 receptor binding of blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptors antagonist, in vitro and in vivo. Blonanserin showed the most potent binding affinity for human D3 receptors among the tested atypical antipsychotics (risperidone, olanzapine and aripiprazole). Our GTPγS-binding assay demonstrated that blonanserin acts as a potent full antagonist for human D3 receptors. All test-drugs exhibited antipsychotic-like efficacy in methamphetamine-induced hyperactivity in rats. Treatment with blonanserin at its effective dose blocked the binding of [(3)H]-(+)-PHNO, a D2/D3 receptor radiotracer, both in the D2 receptor-rich region (striatum) and the D3 receptor-rich region (cerebellum lobes 9 and 10). On the other hand, the occupancies of other test-drugs for D3 receptors were relatively low. In conclusion, we have shown that blonanserin, but not other tested antipsychotics, extensively occupies D3 receptors in vivo in rats. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  20. [Functional status and quality of life in Latin American outpatients with schizophrenia treated with atypical or typical antipsychotics: outcomes of the 12 months schizophrenia outpatient health outcomes (IC-SOHO) Study].

    Science.gov (United States)

    Rovner, Jorge; Assunção, Sheila; Gargoloff, Pedro; Ibarra, Hernan Silva; Gasca, Jaime Aguilar; Fournais, Erick Landa; Adan, Pablo; Andrades, Nestor J; Dyachkova, Yulia

    2005-01-01

    Functional status and quality of life outcomes in Latin American outpatients with schizophrenia were compared after 12 months of monotherapy treatment with olanzapine, risperidone or typical antipsychotics. Both outcomes were assessed as part of a prospective, large (N= 7658), international (27 countries), observational study. from the Latin American subpopulation (N= 2671; 11 countries) are presented. Compared to typical antipsychotics, olanzapine and risperidone were associated with significantly (p < 0.05) greater odds of employment and social activity, and significantly greater improvements in quality of life. Olanzapine was also associated with significantly greater odds of living independently, compared to typical antipsychotics. This study indicates that functional status and quality of life outcomes are likely to be more favorable when Latin American outpatients with schizophrenia are treated with olanzapine or risperidone monotherapy, rather than typical antipsychotics.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Changes in antipsychotics and other psychotropic drugs during a 30-month lifestyle intervention among outpatients with schizophrenia

    DEFF Research Database (Denmark)

    Højlund, Mikkel; Elliott, Anja Friis; Madsen, Nikolaj Juul

    2017-01-01

    BACKGROUND: Patients with schizophrenia have high risk of early death from diabetes and cardiovascular diseases, partly because of poor lifestyle and partly because of long-lasting exposure to antipsychotic treatment. AIMS: To investigate the influence of a lifestyle intervention program on changes...... in psychotropic medication in a non-selected cohort of patients with schizophrenia. METHODS: Observational study of outpatients in the Central Denmark Region during a 30-month lifestyle program. RESULTS: One hundred and thirty-six patients were enrolled and 130 were available for analysis. Median follow-up time......, follow-up time and time since diagnosis. The number of prescriptions was significantly higher in the patients who decreased their DDD and the proportion of antipsychotic depot formulation was higher in those who increased their DDD. CONCLUSIONS: Most patients decreased or stabilized their total dose...

  3. Determinants of first- and second-generation antipsychotic drug use in clinically unstable patients with schizophrenia treated in four European countries

    NARCIS (Netherlands)

    Barbui, Corrado; Nosè, Michela; Mazzi, Maria Angela; Bindman, Jonathan; Leese, Morven; Schene, Aart; Becker, Thomas; Angermeyer, Matthias C.; Koeter, Maarten; Gray, Richard; Tansella, Michele

    2006-01-01

    The present study investigated the use of antipsychotics in a sample of clinically unstable patients with schizophrenia who were recruited in four European sites. The study aimed: (i) to test whether the length of previous antipsychotic exposure was associated with the choice of antipsychotic

  4. Blonanserin, an antipsychotic and dopamine D₂/D₃receptor antagonist, and ameliorated alcohol dependence.

    Science.gov (United States)

    Takaki, Manabu; Ujike, Hiroshi

    2013-01-01

    Blonanserin (BNS) is used for treatment of both positive and negative symptoms of schizophrenia in Japan and Korea. Because BNS has weak α1 receptor blocking activities and is almost devoid of histamine H1 and muscarinic M1 antagonist activity, BNS is better tolerated than other atypical antipsychotics. A high degree of D₃ receptor blockage is reported to be predictive of drug abuse and alcoholism, and BNS has strong D₃ receptor antagonism. Thus, BNS may be useful in the treatment of alcoholism. We present a case in which BNS ameliorated alcohol dependence.

  5. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

  6. Atypical Depression

    Science.gov (United States)

    Atypical depression Overview Any type of depression can make you feel sad and keep you from enjoying life. However, atypical depression — also called depression with atypical features — means that ...

  7. Newer antipsychotics and upcoming molecules for schizophrenia.

    Science.gov (United States)

    George, Melvin; Amrutheshwar, Radhika; Rajkumar, Ravi Philip; Kattimani, Shivanand; Dkhar, Steven Aibor

    2013-08-01

    The management of schizophrenia has seen significant strides over the last few decades, due to the increasing availability of a number of antipsychotics. Yet, the diminished efficacy in relation to the negative and cognitive symptoms of schizophrenia, and the disturbing adverse reactions associated with the current antipsychotics, reflect the need for better molecules targeting unexplored pathways. To review the salient features of the recently approved antipsychotics; namely, iloperidone, asenapine, lurasidone and blonanserin. We discuss the advantages, limitations and place in modern pharmacotherapy of each of these drugs. In addition, we briefly highlight the new targets that are being explored. Promising strategies include modulation of the glutamatergic and GABAergic pathways, as well as cholinergic systems. Although regulatory bodies have approved only a handful of antipsychotics in recent years, the wide spectrum of targets that are being explored could eventually bring out antipsychotics with improved efficacy and acceptability, as well as the potential to revolutionize psychiatric practice.

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

    DEFF Research Database (Denmark)

    Weeke, Peter; Jensen, Aksel; Folke, Fredrik

    2014-01-01

    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 OHCA in Denmark (2001-2010). Risk of OHCA associated with antipsychotic drug...

  9. Comparing the side effect profile of the Atypical

    African Journals Online (AJOL)

    antipsychotics have greater efficacy (especially for negative symptoms) and fewer EPSE when compared to the typical antipsychotics. Given the lack of studies directly comparing these agents, we used the Physician Desk Reference (PDR) to calculate the treatment emergent placebo adjusted side effects for these atypical ...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Antipsychotics for fibromyalgia in adults.

    Science.gov (United States)

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

    2016-06-02

    This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms. To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults. We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors. We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults. We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the

  12. Atypical pneumonia

    Science.gov (United States)

    Walking pneumonia; Community-acquired pneumonia - atypical ... Bacteria that cause atypical pneumonia include: Mycoplasma pneumonia is caused by the bacteria Mycoplasma pneumoniae . It often affects people younger than age 40. Pneumonia due ...

  13. Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum.

    Science.gov (United States)

    Hiroi, N; Graybiel, A M

    1996-10-07

    Atypical and typical neuroleptics, when administered chronically, can bring about profound but contrasting changes in schizophrenic symptoms and motor activation and dramatically modulate brain neurochemistry. To explore the transcriptional events that might be involved in this neurochemical regulation, we used immunohistochemistry and immunoblotting to examine the expression patterns of two bZip transcription factors, c-Fos and FosB, in the striatum of rats treated acutely and chronically with neuroleptic drugs of different classes. Typical and atypical neuroleptic drugs produced contrasting regulatory effects on a FosB-like protein of ca. 36-39 kDa, the molecular weight of truncated FosB (delta FosB). Chronic treatments with two typical neuroleptics, haloperidol and metoclopramide, but not with the atypical neuroleptic clozapine, led to markedly enhanced FosB-like immunoreactivity in the caudoputamen. Further, c-Fos-like protein in the striatum, considered a marker for the induction of antipsychotic actions by neuroleptic treatments, was downregulated by chronic treatment with the two potent antipsychotic drugs tested, but not by chronic treatment with metoclopramide, which has low antipsychotic efficacy but induces extrapyramidal side effects. These results suggest that chronic treatments with neuroleptics having different effects on cognitive and motor behavior induce different long-term changes in transcription factor expression in the striatum. Nevertheless, we found that neuroleptics of both classes regulated transcription factor expression in overlapping populations of striatal neurons expressing enkephalin or DARPP-32. Contrasting patterns of transcriptional regulation in these neurons may thus contribute to the distinct neurochemical and behavioral effects that characterize neuroleptics of different classes.

  14. Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, 
Present and Future

    Science.gov (United States)

    Li, Peng; Snyder, Gretchen L.; Vanover, Kimberly E.

    2016-01-01

    Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the world’s population. This disease is associated with considerable morbidity placing a major financial burden on society. Antipsychotics have been the mainstay of the pharmacological treatment of schizophrenia for decades. The traditional typical and atypical antipsychotics demonstrate clinical efficacy in treating positive symptoms, such as hallucinations and delusions, while are largely ineffective and may worsen negative symptoms, such as blunted affect and social withdrawal, as well as cognitive function. The inability to treat these latter symptoms may contribute to social function impairment associated with schizophrenia. The dysfunction of multiple neurotransmitter systems in schizophrenia suggests that drugs selectively targeting one neurotransmission pathway are unlikely to meet all the therapeutic needs of this heterogeneous disorder. Often, however, the unintentional engagement of multiple pharmacological targets or even the excessive engagement of intended pharmacological targets can lead to undesired consequences and poor tolerability. In this article, we will review marketed typical and atypical antipsychotics and new therapeutic agents targeting dopamine receptors and other neurotransmitters for the treatment of schizophrenia. Representative typical and atypical antipsychotic drugs and new investigational drug candidates will be systematically reviewed and compared by reviewing structure-activity relationships, pharmacokinetic properties, drug metabolism and safety, pharmacological properties, preclinical data in animal models, clinical outcomes and associated side effects. PMID:27291902

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

    Science.gov (United States)

    Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

    2006-01-01

    Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship 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.

  16. The Impact of Cannabis Use on the Dosage of Antipsychotic Drugs in Patients Admitted on the Psychiatric Ward at the University Hospital of the West Indies

    Directory of Open Access Journals (Sweden)

    P Thomas

    2015-03-01

    Full Text Available Objective: To assess the impact of cannabis use on the efficacy of antipsychotic drugs in male subjects presenting to the University Hospital of the West Indies (UHWI with psychotic episodes. Methods: Male subjects, 18–40 years old, admitted to the psychiatric ward of the UHWI between February 2013 and May 2013, diagnosed with schizophrenia, schizophreniform disorder and who tested positive for ∆9-tetrahydrocannabinol were recruited for the study. On day one, consenting subjects were assessed using the Brief Psychiatric Rating Scale (BPRS. Patients were prescribed seven days of an oral antipsychotic medication (haloperidol, chlorpromazine, risperidone, quetiapine, olanzapine. Medicated subjects were then reassessed using the BPRS on days three and seven. Statistical analysis involved the use of Student’s t-test and repeated measure analysis of variance. Results: In total, 20 subjects were recruited (mean age = 26.00 ± 5.96 years. Subjects were grouped based on the daily chlorpromazine equivalent (CPZE dose given on day one into CPZE1 (CPZE dose of 100–300mg; n = 8 and CPZE2 (CPZE dose of 400–1250 mg; n = 12. There was no significant difference in the total BPRS score between the groups on day one (CPZE1 = 41.38 ± 16.47 versus CPZE2 = 49.42 ± 25.58; p = 0.44; similar findings were obtained for the positive (26.75 ± 9.27 versus 31.83 ± 17.30; p = 0.46 and negative (14.63 ± 7.73 versus 17.58 ± 9.74; p = 0.48 symptom component on the BPRS. For subjects in CPZE1, there was no significant decrease in total BPRS score [F(2,21 = 0.07, p = 0.93] over the study period. For CPZE2, significant reduction in total BPRS scores was achieved [F(2,33 =7.12, p = 0.01], contributed by significant decrease in the positive [F(2,33 = 5.64, p = 0.02 and negative [F(2,33 = 7.53, p = 0.01 symptom components of the BPRS. Conclusion: The findings of this study purport that male cannabis users presenting with psychotic disorders may not achieve optimal

  17. Atypical Depression

    Directory of Open Access Journals (Sweden)

    Erhan Ertekin

    2013-09-01

    Full Text Available Atypical depression is defined as a specifier of major depressive disorder. Columbia criteria for atypical depression are commonly used to make a diagnosis. Female sex, onset at early age, chronic course, and higher rate of comorbidity (especially anxiety disorder and bipolar disorder is noteworthy in atypical depression. Although, the atypical depression seems to support the familial genetic transition, there is not any specific study supporting these data. In the treatment of atypical depression, monoamine oxidase inhibitors are reported to be more effective than tricyclic antidepressants. In recent studies, selective serotonin reuptake inhibitors have also proven to be efficient.

  18. Assessment of antipsychotic prescribing in Belgian nursing homes.

    Science.gov (United States)

    Azermai, Majda; Elseviers, Monique; Petrovic, Mirko; van Bortel, Luc; Stichele, Robert Vander

    2011-10-01

    Given the potential adverse effects of antipsychotics, high use in nursing homes creates concern. Our study goal was to explore the use of antipsychotics in relation to resident characteristics, and to assess the appropriateness of antipsychotic prescribing in Belgian nursing homes. Data were used from a cross-sectional study (Prescribing in Homes for the Elderly; PHEBE) conducted in 76 nursing homes in Belgium. Antipsychotics were classified into typical and atypical, using the anatomical therapeutic and chemical classification. Ten inappropriate antipsychotic prescribing indicators were selected from the updated Beers criteria (2003), Bergen District Nursing Home Study (BEDNURS) indicators, and Screening Tool of Older People's Prescriptions criteria (STOPP). The residents' mean age was 84.8 years, 78.1% of whom were female. The prevalence of antipsychotic utilization was 32.9%. Antipsychotics were mainly indicated for dementia-related agitation, and psychosis with/without dementia. Higher use of antipsychotics was found for dementia (OR: 3.27; 95% CI: 2.61-4.09), insomnia (OR: 1.38; 95% CI: 1.10-1.73), depression (OR: 1.30; 95% CI: 1.03-1.65), and age antipsychotic prescribing indicators scoring the highest among users were: long-term use (92.6%), use despite risk of falling (45.6%), combined use with other psychotropics (31.8%), and duplicate use (15.1%). Inappropriate prescribing was associated with depression (OR: 3.41) and insomnia (OR: 2.17). The indicator-driven analysis of antipsychotic prescribing quality revealed a need for improvement, with the main prescribing problems relating to duration and combination of therapies. Risks/benefits of off-label use need to be evaluated more consciously at the start of therapy, and at periodic re-evaluations.

  19. Antidepressants but not antipsychotics have antiepileptogenic effects with limited effects on comorbid depressive-like behaviour in the WAG/Rij rat model of absence epilepsy.

    Science.gov (United States)

    Citraro, Rita; Leo, Antonio; De Fazio, Pasquale; De Sarro, Giovambattista; Russo, Emilio

    2015-06-01

    Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behaviour in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6-month-old) rats after a chronic 7 weeks treatment. ELTT with all antipsychotics did not affect the development of seizures, whereas, both ELTT haloperidol (1 mg · kg(-1) day(-1)) and risperidone (0.5 mg · kg(-1) day(-1)) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30 mg · kg(-1) day(-1)) and duloxetine (10-30 mg · kg(-1) day(-1)) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30 mg · kg(-1) day(-1) reduced immobility time while at 10 mg · kg(-1) day(-1) an increase was observed. In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive-like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive-like behaviour. © 2015 The British Pharmacological Society.

  20. Effects of typical antipsychotic, haloperidol on regional cerebral blood flow in drug-naive schizophrenic patients-study with 99mTc-HMPAO SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kamoya, Masatoshi [Kanazawa Medical Univ., Ishikawa (Japan)

    2001-03-01

    For the purpose of examining antipsychotic action of haloperidol (HPD), effects of chronic perioral administration of HPD 4.5 mg/day on regional cerebral blood flow (rCBF) with 99mTc-HMPAO SPECT were investigated in 12 drug-naive schizophrenic patients with acute hallucinatory and delusional state. Further, the SPECT examinations were performed on 20 normal adult volunteers to investigate differences in rCBFs between schizophrenics and the normal subjects. Results are itemized as follows. The rCBF values were significantly increased in the bilateral superior and middle frontal, cingulate, middle temporal, pre-and post-central gyri, the left superior temporal gyrus, the bilateral inferior parietal lobule, and the bilateral hippocampal and thalamic cortices in comparison between normal subjects and before the HPD dose in schizophrenics. However, the rCBF values after the HPD dose showed significant increases only in the bilateral pre-and post-central gyri in comparison with the normal subjects. The rCBF values were significantly decreased in the bilateral superior, middle and inferior frontal, superior and middle temporal gyri, and the left insular gyrus after the HPD dose in comparison with before the HPD dose. The psychiatric assessment with PANSS showed an improvement of positive symptoms consisting of auditory hallucination and delusions after the HPD dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the HPD dose showed positive correlations between the right inferior frontal gyrus and auditory hallucination or positive symptoms, between the right superior temporal gyrus, left thalamus and delusions, and between the left thalamus, insular gyrus and negative symptoms. These results suggest that acute drug-naive schizophrenic patients have widespread cortico-subcortical energic hypermetabolism and HPD reduces the hypermetabolism, leading to whole normalized brain metabolism, in particular with the larger region

  1. Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder.

    Science.gov (United States)

    Abdolmaleky, Hamid M; Pajouhanfar, Sara; Faghankhani, Masoomeh; Joghataei, Mohammad Taghi; Mostafavi, Ashraf; Thiagalingam, Sam

    2015-12-01

    Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. © 2015 Wiley Periodicals, Inc.

  2. 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:

  3. Hypothermia due to Antipsychotic Medication : A Systematic Review

    NARCIS (Netherlands)

    Zonnenberg, Cherryl; Bueno-de-Mesquita, Jolien M.; Ramlal, Dharmindredew; Blom, Jan Dirk

    2017-01-01

    Background: Hypothermia is a rare, but potentially fatal adverse effect of antipsychotic drug (APD) use. Although the opposite condition, hyperthermia, has been researched extensively in the context of the malignant antipsychotic syndrome, little is known about hypothermia due to APDs. Objective:

  4. Cavitary pulmonary nodules in atypical collagen disease and lupoid drug reaction. Report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Muren, C.; Strandberg, O.

    The case histories of two patients with cavitary pulmonary nodules and the findings at chest radiography are reviewed. The first patient had a connective tissue disease with features common to systematic lupus erythematosus and Wegener's granulomatosis. In the second patient the lung changes developed as part of a drug reaction to carbamezapine and/or phenytoin. The common denominator of the cavitating nodules is probably the presence of granulomas, developing as a sequela of pulmonary vasculitis. (orig.).

  5. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  6. Pharmaco-epidemiological description of the population of the Marche Region (central Italy treated with the antipsychotic drug olanzapine

    Directory of Open Access Journals (Sweden)

    Fiorenzo Mignini

    2013-03-01

    Full Text Available BACKGROUND. In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA promulgated a cautionary note. MATERIALS AND METHODS. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. RESULTS. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. CONCLUSIONS. Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

  7. Incident users of antipsychotics

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kruse, Marie

    2016-01-01

    PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine...... initial antipsychotic prescribing patterns and associated use of mental health care services. METHOD: Population-based cohort study linking the following Danish national registers: the Central Psychiatric Research Register, the Register of Medicinal Product Statistics, and Statistics Denmark. RESULTS...

  8. Combination of experimental and in silico methods for the assessment of the phototransformation products of the antipsychotic drug/metabolite Mesoridazine.

    Science.gov (United States)

    Wilde, Marcelo L; Menz, Jakob; Leder, Christoph; Kümmerer, Klaus

    2018-03-15

    The lack of studies on the fate and effects of drug metabolites in the environment is of concern. As their parent compounds, metabolites enter the aquatic environment and are subject to biotic and abiotic process. In this regard, photolysis plays an important role. This study combined experimental and in silico quantitative structure-activity relationship (QSAR) methods to assess the fate and effects of Mesoridazine (MESO), a pharmacologically active human drug and metabolite of the antipsychotic agent Thioridazine, and its transformation products (TPs) formed through a Xenon lamp irradiation. After 256min, the photodegradation of MESO⋅besylate (50mgL -1 ) achieved 90.4% and 6.9% of primary elimination and mineralization, respectively. The photon flux emitted by the lamp (200-600nm) was 169.55Jcm -2 . Sixteen TPs were detected by means of liquid chromatography-high resolution mass spectrometry (LC-HRMS), and the structures were proposed based on MS n fragmentation patterns. The main transformation reactions were sulfoxidation, hydroxylation, dehydrogenation, and sulfoxide elimination. A back-transformation of MESO to Thioridazine was evidenced. Aerobic biodegradation tests (OECD 301 D and 301F) were applied to MESO and the mixture of TPs present after 256min of photolysis. Most of TPs were not biodegraded, demonstrating their tendency to persist in aquatic environments. The ecotoxicity towards Vibrio fischeri showed a decrease in toxicity during the photolysis process. The in silico QSAR tools QSARINS and US-EPA PBT profiler were applied for the screening of TPs with character of persistence, bioaccumulation, and toxicity (PBT). They have revealed the carbazole derivatives TP 355 and TP 337 as PBT/vPvB (very persistent and very bioaccumulative) compounds. In silico QSAR predictions for mutagenicity and genotoxicity provided by CASE Ultra and Leadscope® indicated positive alerts for mutagenicity on TP 355 and TP 337. Further studies regarding the carbazole

  9. The quality of lactation studies including antipsychotics

    NARCIS (Netherlands)

    Hummels, Hazel; Bertholee, Daphne; van der Meer, Douwe; Smit, Jan Pieter; Wilffert, Bob; ter Horst, Peter

    2016-01-01

    The aim of this study is to determine the quality of lactation studies that investigated antipsychotics in breast milk according to the Food and Drug Administration (FDA) and International Lactation Consultant Association (ILCA) draft guidelines. We used the draft FDA and ILCA guidelines to review

  10. Atypical responses in patients with advanced melanoma, lung cancer, renal-cell carcinoma and other solid tumors treated with anti-PD-1 drugs: A systematic review.

    Science.gov (United States)

    Queirolo, Paola; Spagnolo, Francesco

    2017-09-01

    Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were recently approved for the treatment of advanced melanoma and other solid tumors. Atypical patterns of response (i.e. tumor shrinkage or stabilization after initial progression) were observed in about 10% of metastatic melanoma patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug ipilimumab and were associated with improved survival; however, the rate of atypical response patterns to anti-PD-1 therapy is not clear. An electronic search was performed to identify clinical trials evaluating response to anti-PD-1 therapy with nivolumab and pembrolizumab in patients with advanced solid tumors. Thirty-eight studies were included in our analysis for a total of 7069 patients with advanced cancer treated with anti-PD-1 therapy. Responses were evaluated by unconventional response criteria in 19 trials and were observed for all cancer types but tumors with mismatch-repair deficiency and head and neck squamous cell carcinoma. Overall, 151 atypical responses were observed in 2400 patients (6%) evaluated by unconventional response criteria. The results of our systematic review highlight the clinical relevance of unconventional responses to anti-PD-1 therapy and support further investigation into the development of tools that may assist evaluation of the antitumor activity of immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The influence of clozapine treatment and other antipsychotics on the 18 kDa translocator protein, formerly named the peripheral-type benzodiazepine receptor, and steroid production.

    Science.gov (United States)

    Danovich, Lena; Veenman, Leo; Leschiner, Svetlana; Lahav, Michal; Shuster, Vered; Weizman, Abraham; Gavish, Moshe

    2008-01-01

    It has been shown that the atypical antipsychotic drug clozapine increases the levels of the neurosteroid allopregnanolone in the rat brain. The 18 kDa translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been demonstrated to be involved in the process of steroid biosynthesis, in peripheral steroidogenic tissues as well as in glia cells in the brain. In the current study, we investigated the influence of chronic treatment with clozapine and other antipsychotics (thioridazine,sulpiride and risperidone) on TSPO binding in cell cultures and rat tissues. Clozapine significantly increased TSPO binding density in C6 rat glioma cells and in MA-10 mouse Leydig tumor cells, while the antipsychotic sulpiride had no effect on TSPO binding density in both cell lines. In addition, clozapine, but not sulpiride, significantly increased progesterone synthesis by MA-10 Leydig tumor cells. In an animal experiment, male Sprague-Dawley rats were treated with clozapine (20 mg/kg), risperidone (0.5 mg/kg), thioridazine (20 mg/kg), or sulpiride (20 mg/kg) for 21 days, followed by 7 days of withdrawal. Clozapine induced significant increases in TSPO binding in brain and peripheral steroidogenic tissues, whereas the other antipsychotics did not show such pronounced effects on TSPO binding. Our results suggest that TSPO may be involved in the modulation of steroidogenesis by clozapine.

  12. A consensus guideline for antipsychotic drug use for dementia in care homes. Bridging the gap between scientific evidence and clinical practice

    NARCIS (Netherlands)

    Zuidema, Sytse U.; Johansson, Alice; Selbaek, Geir; Murray, Matt; Burns, Alistair; Ballard, Clive; Koopmans, Raymond T. C. M.

    2015-01-01

    Background: To produce a practice guideline that includes a set of detailed consensus principles regarding the prescription of antipsychotics (APs) amongst people with dementia living in care homes. Methods: We used a modified Delphi consensus procedure with three rounds, where we actively specified

  13. Off-label utilization of antipsychotics

    African Journals Online (AJOL)

    Adele

    clozapine, olanzapine, risperidone, quetiapine and amisulpride. All other antipsychotics were classed as conventional antipsychotics. Among the conventional antipsychotics, two subclasses were identified: “sedative” and “high potency”. Sedative antipsychotics were levomepromazine, promazine, clothiapine, thioridazine, ...

  14. Atypical psychotic symptoms and Dandy-Walker variant.

    Science.gov (United States)

    Williams, Aislinn J; Wang, Zhenni; Taylor, Stephan F

    2016-10-01

    New-onset psychotic symptoms often respond well to antipsychotic treatment; however, symptoms may be difficult to treat when an underlying brain malformation is present. Here, we present a case of atypical psychotic symptoms in the context of a congenital cerebellar malformation (Dandy-Walker variant). The patient ultimately improved with paliperidone palmitate after multiple antipsychotic medication trials (both oral and one long-acting injectable) were ineffective. Neuroimaging may provide valuable diagnostic and prognostic information in cases of new-onset psychosis with atypical features and treatment resistance, even in the absence of neurologic signs and symptoms.

  15. Antipsychotic agents: efficacy and safety in schizophrenia

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2012-11-01

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

  16. Atypical Antidepressants

    Science.gov (United States)

    ... which is also used to treat insomnia Vortioxetine (Trintellix) Side effects may occur with antidepressants, including atypical ... traz_imtb_ins.pdf. Accessed May 23, 2016. Trintellix (prescribing information). Deerfield, Ill.: Takeda Pharmaceuticals; 2016. http:// ...

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

    Science.gov (United States)

    Tuplin, Erin W; Holahan, Matthew R

    2017-11-14

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

  18. Treatment of Diabetic Ketoacidosis Associated With Antipsychotic Medication: Literature Review.

    Science.gov (United States)

    Vuk, Antonia; Baretic, Maja; Osvatic, Martina Matovinovic; Filipcic, Igor; Jovanovic, Nikolina; Kuzman, Martina Rojnic

    2017-10-01

    The second-generation antipsychotics (SGAs) are associated with metabolic disturbances. Diabetic ketoacidosis (DKA) is a rare, but potentially fatal sign of acute glucose metabolism dysregulation, which may be associated with the use of SGAs. This study aims to review published reports of patients with schizophrenia and antipsychotic drug-associated DKA, focusing on the effective management of both conditions. Using a predefined search strategy, we searched PubMed and EMBASE from their inception to July 2016. The search terms were related to "diabetic ketoacidosis" and "antipsychotic medication." Case reports, case series, and reviews of case series written in English language were included in the review. Sixty-five reports were analyzed. In most patients who developed antipsychotic-associated DKA, 1 or more suspected antipsychotic medications were discontinued. In 5 cases, a rechallenge test was trialed, and in only 1 case, it resulted in the elevation of blood glucose. The majority was subsequently treated with a different SGA in combination with insulin/oral hypoglycemic agents; although approximately a third of patients had a complete resolution of symptoms or could control diabetes with diet only at the point of discharge. Patients taking antipsychotic medications should be regularly screened for insulin resistance and educated about potential complications of antipsychotic medications. This will allow clinicians to individualize treatment decisions and reduce iatrogenic contribution to morbidity and mortality. To achieve best treatment outcomes, antipsychotic-induced DKA should be treated jointly by psychiatry and endocrinology teams.

  19. Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Laura R. Magni

    2017-03-01

    Full Text Available Objective: To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program on weight gain compared with a treatment-as-usual (TAU approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI variation and clinical variables. Method: Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59 and control (n=26. The Superwellness Program (experimental group consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks, and after 6 months. Results: BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021. Duration of illness moderated the effect of treatment on BMI (p = 0.026. No significant (p = 0.499 effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024 reduction in metabolic risk by reducing BMI. Conclusion: A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

  20. Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs.

    Science.gov (United States)

    Magni, Laura R; Ferrari, Clarissa; Rossi, Giuseppe; Staffieri, Elena; Uberti, Aldo; Lamonaca, Dario; Boggian, Ileana; Merlin, Silvia; Primerano, Giuseppe; Mombrini, Alessandra; Poli, Roberto; Saviotti, Francesco M; Caldera, Maria T; Zanotti, Luciana; Rossi, Roberta

    2017-01-01

    To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program) on weight gain compared with a treatment-as-usual (TAU) approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI) variation and clinical variables. Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59) and control (n=26). The Superwellness Program (experimental group) consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks), and after 6 months. BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021). Duration of illness moderated the effect of treatment on BMI (p = 0.026). No significant (p = 0.499) effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024) reduction in metabolic risk by reducing BMI. A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

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

    Directory of Open Access Journals (Sweden)

    Jingchun Sun

    2013-01-01

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

  2. 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.

  3. Atypical Cities

    Science.gov (United States)

    DiJulio, Betsy

    2011-01-01

    In this creative challenge, Surrealism and one-point perspective combine to produce images that not only go "beyond the real" but also beyond the ubiquitous "imaginary city" assignment often used to teach one-point perspective. Perhaps the difference is that in the "atypical cities challenge," an understanding of one-point perspective is a means…

  4. Atypical Depression

    Science.gov (United States)

    ... coping Other mental health disorders such as anxiety Suicide from feelings of depression Prevention There's no sure way to prevent depression. ... the association between oversleeping and overeating in atypical depression. Journal of Psychosomatic Research. 2015;78:52. Koyuncu A, et al. Relationship ...

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

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Antipsychotic Prescriptions for Children Aged 5 Years or Younger

    Directory of Open Access Journals (Sweden)

    Ana Lòpez-De Fede

    2014-10-01

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

  8. Antipsychotic prescription and mortality in hospitalized older persons.

    Science.gov (United States)

    Chiesa, Deborah; Marengoni, Alessandra; Nobili, Alessandro; Tettamanti, Mauro; Pasina, Luca; Franchi, Carlotta; Djade, Codjo D; Corrao, Salvatore; Salerno, Francesco; Marcucci, Maura; Romanelli, Giuseppe; Mannucci, Pier Mannuccio

    2017-11-01

    Recent scientific reports have shown that older persons treated with antipsychotics for dementia-related behavioural symptoms have increased mortality. However, the impact of these drugs prescribed during hospitalization has rarely been assessed. We aimed to investigate whether antipsychotics are associated with an increased risk of mortality during hospitalization and at 3-month follow-up in elderly inpatients. We analyzed data gathered during two waves (2010 and 2012) by the REPOSI (Registro Politerapie Società Italiana Medicina Interna). All new prescriptions of antipsychotic drugs during hospitalization, whether maintained or discontinued at discharge, were collected, and logistic regression models were used to analyze their association with in-hospital and 3-month mortality. Covariates were age, sex, the Short Blessed Test (SBT) score, and the Cumulative Illness Rating Scale. Among 2703 patients included in the study, 135 (5%) received new prescriptions for antipsychotic drugs. The most frequently prescribed antipsychotic during hospitalization and eventually maintained at discharge was haloperidol (38% and 36% of cases, respectively). Patients newly prescribed with antipsychotics were older and had a higher Cumulative Illness Rating Scale comorbidity index both at admission and at discharge compared to those who did not receive a prescription. Of those prescribed antipsychotics, 71% had an SBT score ≥10 (indicative of dementia), 12% had an SBT score of 5-9 (indicative of questionable dementia); and 17% had an SBT score <5 (indicative of normal cognition). In-hospital mortality was slightly higher in patients prescribed antipsychotic drugs (14.3% vs 9.4%; P = 0.109), but in multivariate analysis only male sex, older age, and higher SBT scores were significantly related to mortality during hospitalization. At 3-month follow-up, only male sex, older age, and higher SBT scores were associated with mortality. We found that the prescription of antipsychotic

  9. New drugs of abuse.

    Science.gov (United States)

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

    2015-02-01

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

  10. 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

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

    Science.gov (United States)

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

    2006-01-01

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

  12. 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....

  13. Prescription pattern and cost analysis of antipsychotics in a tertiary ...

    African Journals Online (AJOL)

    The percentage of encounters in which an antibiotic or injection was prescribed was 2.0% (n=11) and 40.9% (n=221) respectively. The percentage of drugs prescribed by generic name and from essential drug list was 92.5% (n=1165) and 70.0% (n=880) respectively. The oral antipsychotics prescribed (86%) included ...

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  15. [Atypical odontalgia].

    Science.gov (United States)

    Türp, Jens Christoph

    2005-01-01

    In spite of its first description by the English surgeon JOHN HUNTER more than 200 years ago, atypical odontalgia (AO), or phantom tooth pain, is not universally known among dentists. AO is a persistent neuropathic pain which may be initiated after deafferentiation of trigeminal nerve fibers following root canal treatment, apicectomy, or tooth extraction. In the absence of pathological clinical or radiological findings, the diagnosis is made by exclusion. After a thorough patient education about the condition, pharmacological and psychological pain management is required. Invasive and irreversible treatment attempts are contraindicated.

  16. Atypical antipsychotics as augmentation therapy in anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    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.

  17. Atypical antipsychotics as augmentation therapy in anorexia nervosa.

    Science.gov (United States)

    Marzola, Enrica; Desedime, Nadia; Giovannone, Cristina; Amianto, Federico; Fassino, Secondo; Abbate-Daga, Giovanni

    2015-01-01

    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.

  18. Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics

    Directory of Open Access Journals (Sweden)

    Lauren Klein

    2017-02-01

    Full Text Available Introduction: Case reports and poison center data have demonstrated that the second-generation antipsychotic quetiapine is being obtained and used for recreational abuse. The purpose of this study was to describe the relative rates of single-substance abuse for different atypical antipsychotics and compare their demographic and clinical features. Methods: We conducted a 10-year retrospective analysis of the National Poison Data System (NPDS database (2003 – 2013. Trained nurses and pharmacists with specialty training in toxicology prospectively collect all NPDS data at poison control centers around the United States. We queried the NPDS for all cases of single-substance second-generation antipsychotic exposures coded as “intentional abuse.” The data provided by the NPDS regarding rates and clinical features of quetiapine abuse and the abuse of all other second-generation antipsychotics were compared and described descriptively. Results: During the study period, 2,118 cases of quetiapine abuse and 1,379 cases of other secondgeneration antipsychotic abuse were identified. Quetiapine abuse was more common than the abuse of other second-generation antipsychotics, compromising 60.6% of all abuse cases during the study period. After quetiapine, the next most frequently abused medications were risperidone (530 cases, 15.2% and olanzapine (246 cases, 7.0%. For all second-generation antipsychotics including quetiapine, central nervous system clinical effects were most common, including drowsiness, confusion, and agitation. Other serious clinical effects observed with second-generation antipsychotic abuse included hypotension, respiratory depression, and seizures. Conclusion: Quetiapine abuse is relatively common, and is abused far more often than any other second-generation antipsychotic. Emergency physicians should be aware of the clinical effects that may occur after second-generation antipsychotic abuse. [West J Emerg Med. 2017;18(2243-250.

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

    Science.gov (United States)

    Apiquian, Rogelio; Fresán, Ana; de la Fuente-Sandoval, Camilo; Ulloa, Rosa-Elena; Nicolini, Humberto

    2004-04-27

    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. 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. 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. 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 Mexican physicians to change their prescription pattern. It is

  20. Variation in use of antipsychotic medications in nursing homes in the United States: A systematic review.

    Science.gov (United States)

    Cioltan, Hannah; Alshehri, Samah; Howe, Carol; Lee, Jeannie; Fain, Mindy; Eng, Howard; Schachter, Kenneth; Mohler, Jane

    2017-01-26

    The use of antipsychotic medications (APMs) in nursing home residents in the U.S. is an increasingly prominent issue and has been associated with increased risk of hospitalization, cardiovascular events, hip fractures, and mortality, among other adverse health events. The Food and Drug Administration has placed a black box warning on these drugs, specifying that they are not meant for residents with dementia, and has asked providers to review their treatment plans. The purpose of this systematic PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)-based review was to summarize original research studies on facility level characteristics contributing to the use of antipsychotics in nursing homes across the United States, in order to investigate the variation of use. We searched Ovid Medline, Embase, Cochrane Library, Web of Science, CINAHL, PsycInfo, and Sociological Abstracts. Articles were selected according to the following criteria: (1) Population of interest: older adults (≥60 years of age) residing in nursing homes (not home-based or inpatient hospital settings) in the U.S. (2) Receiving APMs, typical and/or atypical. Specifically excluded were studies of psychotropic medications such as antidepressants, benzodiazepines, anxiolytics, hypnotics, mood stabilizers, and stimulants. All study designs were considered, though reviews, editorials, letters to the editor and opinion pieces were excluded. An expert consultant panel was consulted to categorize facility characteristics into domains and determine possible etiologies of APM use based upon each characteristic. Nineteen observational studies, both quantitative and qualitative, published from 2000 to 2015, met full inclusion criteria and were included in this review. APM use varied based on multiple facility characteristics across several domains: 1) physical, 2) staffing, 3) occupancy, 4) market, and 5) quality. Variation in use of APMs in U.S. nursing homes based upon facility

  1. CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity.

    Science.gov (United States)

    Siuciak, Judith A; Chapin, Douglas S; McCarthy, Sheryl A; Guanowsky, Victor; Brown, Janice; Chiang, Phoebe; Marala, Ravi; Patterson, Terrell; Seymour, Patricia A; Swick, Andrew; Iredale, Philip A

    2007-02-01

    CP-809,101 is a potent, functionally selective 5-HT(2C) agonist that displays approximately 100% efficacy in vitro. The aim of the present studies was to assess the efficacy of a selective 5-HT(2C) agonist in animal models predictive of antipsychotic-like efficacy and side-effect liability. Similar to currently available antipsychotic drugs, CP-809,101 dose-dependently inhibited conditioned avoidance responding (CAR, ED(50)=4.8 mg/kg, sc). The efficacy of CP-809,101 in CAR was completely antagonized by the concurrent administration of the 5-HT(2C) receptor antagonist, SB-224,282. CP-809,101 antagonized both PCP- and d-amphetamine-induced hyperactivity with ED(50) values of 2.4 and 2.9 mg/kg (sc), respectively and also reversed an apomorphine induced-deficit in prepulse inhibition. At doses up to 56 mg/kg, CP-809,101 did not produce catalepsy. Thus, the present results demonstrate that the 5-HT(2C) agonist, CP-809,101, has a pharmacological profile similar to that of the atypical antipsychotics with low extrapyramidal symptom liability. CP-809,101 was inactive in two animal models of antidepressant-like activity, the forced swim test and learned helplessness. However, CP-809,101 was active in novel object recognition, an animal model of cognitive function. These data suggest that 5-HT(2C) agonists may be a novel approach in the treatment of psychosis as well as for the improvement of cognitive dysfunction associated with schizophrenia.

  2. Antipsychotic medication for early episode schizophrenia

    Science.gov (United States)

    Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

    2014-01-01

    Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications

  3. 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......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...... 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...

  4. Antipsychotic therapy during early and late pregnancy. A systematic review.

    Science.gov (United States)

    Gentile, Salvatore

    2010-05-01

    Both first- (FGAs) and second-generation antipsychotics (SGAs) are routinely used in treating severe and persistent psychiatric disorders. However, until now no articles have analyzed systematically the safety of both classes of psychotropics during pregnancy. DATA SOURCES AND SEARCH STRATEGY: Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs. Search terms were pregnancy, psychotropic drugs, (a)typical-first-second-generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 2008. All articles reporting primary data on the outcome of pregnancies exposed to antipsychotics were acquired, without methodological limitations. Reviewed information was too limited to draw definite conclusions on structural teratogenicity of FGAs and SGAs. Both classes of drugs seem to be associated with an increased risk of neonatal complications. However, most SGAs appear to increase risk of gestational metabolic complications and babies large for gestational age and with mean birth weight significantly heavier as compared with those exposed to FGAs. These risks have been reported rarely with FGAs. Hence, the choice of the less harmful option in pregnancy should be limited to FGAs in drug-naive patients. When pregnancy occurs during antipsychotic treatment, the choice to continue the previous therapy should be preferred.

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

    Science.gov (United States)

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

    2008-01-01

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

  6. Can antipsychotics improve social cognition in patients with schizophrenia?

    Science.gov (United States)

    Kucharska-Pietura, Katarzyna; Mortimer, Ann

    2013-05-01

    Social cognition is described as the higher mental processes that are engaged while people store, process, and use social information to make sense of themselves and others. Aspects of social cognition include emotion perception, social cue interpretation, attribution style, and theory of mind, all of which appear disordered in schizophrenia. Such social cognitive deficits are believed to be important predictors of functional outcome in schizophrenia, therefore they may represent a crucial treatment target. Few studies have evaluated the influence of antipsychotic treatment on these deficits. The purpose of this review is to examine the relationship between antipsychotic treatment and social cognition, whether antipsychotics improve social cognitive function, and if so to explore differential medication effects. Comprehensive searches of PsycINFO and MEDLINE/PUBMED were conducted to identify relevant published manuscripts. Fifteen relevant papers published in English were found, describing original studies. On the basis of this review, we have drawn the following conclusions: first, the results do not engender optimism for the possibility that antipsychotic drugs can specifically facilitate social recovery. Second, the actions of antipsychotics on social cognition are inconclusive, due to lack of standardization across research groups, leading to inconsistencies between study designs, methods used, and medication dosages. Third, large-scale longitudinal investigations are needed to explore the unclear relationships between social cognition, symptoms, and functional outcome. Other non-pharmacological treatments focusing on training patients in the social cognitive areas may hold more promise.

  7. Context-dependent efficacy of a counter-conditioning strategy with atypical neuroleptic drugs in mice previously sensitized to cocaine.

    Science.gov (United States)

    Oliveira-Lima, A J; Marinho, Eav; Santos-Baldaia, R; Hollais, A W; Baldaia, M A; Talhati, F; Ribeiro, L T; Wuo-Silva, R; Berro, L F; Frussa-Filho, R

    2017-02-06

    We have previously demonstrated that treatment with ziprasidone and aripiprazole selectively inhibit the development of behavioral sensitization to cocaine in mice. We now investigate their effects on a counter-conditioning strategy in mice and the importance of the treatment environment for this phenomenon. Evaluate the context-specificity of ziprasidone and aripiprazole on conditioned locomotion to cocaine and cocaine-induced hyperlocomotion and behavioral sensitization in a counter-conditioning strategy in mice. Animals were sensitized with saline or cocaine injections in the open-field apparatus in a 15-day intermittent treatment and subsequently treated with vehicle, 5mg/kg ziprasidone or 0.1mg/kg aripiprazole paired to the open-field or the home-cage for 4 alternate days. Mice were then challenged with saline and cocaine in the open-field apparatus on subsequent days. While treatment with ziprasidone decreased spontaneous locomotion and conditioned locomotion alike, treatment with aripiprazole specifically attenuated the expression of conditioned hyperlocomotion to cocaine. Ziprasidone and aripiprazole had no effects on cocaine-induced conditioned hyperlocomotion observed during saline challenge after drug withdrawal. Treatment with either ziprasidone or aripiprazole when previously given in the cocaine-paired environment attenuated the subsequent expression of behavioral sensitization to cocaine. Animals treated with aripiprazole in the open-field, but not in the home-cage, showed a blunted response to cocaine when receiving a cocaine challenge for the first time. Both neuroleptic drugs showed a context-dependent effectiveness in attenuating long-term expression of cocaine-induced behavioral sensitization when administered in the cocaine-associated environment, with aripiprazole also showing effectiveness in blocking the expression of acute cocaine effects. Copyright © 2016. Published by Elsevier Inc.

  8. Combined HTR2C-LEP Genotype as a Determinant of Obesity in Patients Using Antipsychotic Medication

    NARCIS (Netherlands)

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

    2010-01-01

    Obesity is one of the most serious common somatic adverse effects of atypical antipsychotic agents. Genetic factors partly determine the individual patient's risk of developing obesity during treatment. As weight-regulating mechanisms, such as the leptinergic and serotonergic system, may be

  9. Managing antipsychotic-induced acute and chronic akathisia.

    Science.gov (United States)

    Miller, C H; Fleischhacker, W W

    2000-01-01

    Akathisia is a frequent and common adverse effect of treatment with antipsychotic (neuroleptic) drugs. This syndrome consists of subjective (feeling of inner restlessness and the urge to move) as well as objective components (rocking while standing or sitting, lifting feet as if marching on the spot and crossing and uncrossing the legs while sitting). Antipsychotic-induced akathisia can be classified according to the time of onset in the course of antipsychotic treatment (acute, tardive, withdrawal and chronic akathisia). Reported prevalence rates vary widely between 5 and 36.8%. Numerous risk factors for acute akathisia have been described and the exact pathophysiology of akathisia is still unknown. Since akathisia is a drug-induced adverse effect, optimal management involves its prevention rather than treatment. Standardised titration and the use of novel antipsychotics are successful measures of prevention. This paper reviews different forms of therapeutic approaches for the treatment of akathisia. Based on the available literature, propranolol or other lipophilic beta-blockers seem to be the most consistently effective treatment for acute akathisia. There is nothing in the literature to guide a clinician when treatment with beta-blockers fails. Addition of benzodiazepines would appear to be a sensible next choice, especially if subjective distress persists. If all of these drugs are unsuccessful, amantadine or clonidine can be tried. Other agents that have been investigated include ritanserin, piracetam, valproic acid (sodium valproate) and tricyclic antidepressants. Evidence on the treatment of tardive akathisia is unsatisfactory.

  10. Adherence challenges and long-acting injectable antipsychotic treatment in patients with schizophrenia.

    Science.gov (United States)

    Kirk Morton, N; Zubek, Donna

    2013-03-01

    Medication nonadherence has been associated with persistence of psychotic symptoms, relapse, and hospitalization in patients with schizophrenia. Patients with untreated psychosis are significantly less likely to achieve remission, whereas antipsychotic drug adherence has been associated with recovery. As such, adherence to antipsychotic drug treatment is a key issue for nurses and treatment team members caring for patients who typically are on chronic, progressive disease course. Long-acting injectable (LAI) anti-psychotic drugs, developed to improve adherence and provide and alternative antipsychotic drug treatment fro schizophrenia, have been associated with improved treatment outcomes including reduction of relapse rates approximately 30% and reduction in hospitalizations. However, LAI antipsychotic drugs remain underutilized in the United States despite a growing body of literature supporting positive outcomes of LAI versus oral antipsychotic drugs. Mental health nurses are in a key position to support improved adherence inpatients with schizophrenia through use of practical educational strategies that help patients, family members, and health care providers better understand and manage treatment.

  11. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

    Directory of Open Access Journals (Sweden)

    Wentzel-Larsen Tore

    2009-05-01

    Full Text Available Abstract Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA. The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800. In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in

  12. Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors

    Directory of Open Access Journals (Sweden)

    Eldina Rizvić

    2017-08-01

    Full Text Available Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Studies on lerimazoline are rare, and its pharmacological profile is not completely understood. Here, we analyzed the affinity of lerimazoline for dopamine receptor D2, serotonin 5-HT1A and 5-HT2A receptors and α1-adrenoceptor, and investigated lerimazoline contractile effects in isolated rat thoracic aorta. We also determined the effect of several antagonists on the contractile response to lerimazoline, including prazosin (α1-adrenoceptor antagonist, RX 821002 and rauwolscine (α2-adrenoceptor antagonists, JP 1302 (α2C-adrenoceptor antagonist, methiothepin (non-selective 5-HT receptor antagonist, SB 224289 (5-HT1B receptor antagonist, BRL 15572 (5-HT1D receptor antagonist, and ketanserin (5-HT2A receptor antagonist. Lerimazoline displayed high affinity for the 5-HT1A receptor (Ki = 162.5 nM, similar to the previously reported affinity for the 5-HT1D receptor. Binding affinity estimates (Ki for α1, 5-HT2A, and D2 receptors were 6656, 4202 and 3437.5 nM, respectively (the literature reported Ki for 5-HT1B receptor is 3480 nM. Lerimazoline caused concentration-dependent contractions in 70% of preparations, varying in the range between 40% and 55% of the maximal contraction elicited by phenylephrine. While prazosin reduced the maximum contractile response to lerimazoline, rauwolscine showed a non-significant trend in reduction of the response. Both ketanserin (10 nM and 1 µM and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, α1-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an “atypical” decongestant.

  13. Degradation of the tricyclic antipsychotic drug chlorpromazine under environmental conditions, identification of its main aquatic biotic and abiotic transformation products by LC-MSn and their effects on environmental bacteria.

    Science.gov (United States)

    Trautwein, Christoph; Kümmerer, Klaus

    2012-03-15

    The search for environmental transformation products of organic pollutants (like drugs) is a difficult task and usually only few compounds are detected. This might be due to effective degradation but could also be a result of analytical deficits dealing with complex matrices. Especially transformation products of very low concentrations in sludge were difficult to identify so far. Additionally, the use of standard separation techniques might lead to the loss of isomeric compounds, which possess identical spectroscopic and spectrometric properties. To date no complete study investigating the environmental fate of any tricyclic antipsychotic drug has been reported. Therefore, this study investigated the popular neuroleptic drug chlorpromazine and its potential transformation by all main environmental pathways: aerobic and anaerobic biodegradation as well as abiotic photolytic degradation by sunlight. Analysis of test samples by high performance liquid chromatography coupled to multiple stage mass-spectrometry (HPLC-MS(n)) allowed the detection of numerous compounds. Further, the use of a special software allowed distinguishing between transformation products of small intensities and background "noise" caused by sludge or matrix. Three aerobic tests of different bacterial density (the Closed Bottle test, OECD 301D; the Manometric Respiratory test, OECD 301F; the modified Zahn-Wellens test, 302B; one anaerobic test (a modified anaerobic degradation test according to ISO 11734) as well as a photodegradation test were performed in the present study. According to the individual test guidelines, chlorpromazine had to be classified as not biodegradable in all of the biodegradation tests. However, a special chromatographic column and gradient along with mass spectrometric fragmentation experiments of higher order uncovered the presence of a total of 61 abiotic and biotic transformation products which where formed during the course of the tests. The structures of three

  14. Brain Connectivity Studies in Schizophrenia: Unravelling the Effects of Antipsychotics

    DEFF Research Database (Denmark)

    Nejad, A.B.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte Yding

    2012-01-01

    Impaired brain connectivity is a hallmark of schizophrenia brain dysfunction. However, the effect of drug treatment and challenges on the dysconnectivity of functional networks in schizophrenia is an understudied area. In this review, we provide an overview of functional magnetic resonance imaging...... studies examining dysconnectivity in schizophrenia and discuss the few studies which have also attempted to probe connectivity changes with antipsychotic drug treatment. We conclude with a discussion of possible avenues for further investigation....

  15. Acute Pancreatitis Associated With Antipsychotic Medication: Evaluation of Clinical Features, Treatment, and Polypharmacy in a Series of Cases.

    Science.gov (United States)

    Silva, Matthew A; Key, Sujin; Han, Edward; Malloy, Michael J

    2016-04-01

    Antipsychotic-associated acute pancreatitis presents like pancreatitis from other causes, requiring clinical judgment, tests, and decision support to establish the diagnosis. Many new cases of atypical antipsychotic pancreatitis have been established, and current decision supports are out of date as antipsychotic polypharmacy is being recognized. Given the population frequency of psychosis and frequency of antipsychotic prescribing, we reviewed published cases summarizing common clinical findings and antipsychotics associated with acute pancreatitis to updating earlier decision support. Case reports of antipsychotic pancreatitis from 1990 to 2015 were reviewed and abstracted by independent reviewers. Demographic, clinical features, management, and Naranjo and probability scores were abstracted and reviewed for associations. Appropriate statistical tests were selected for normally and non-normally distributed data. We summarized 41 cases of acute pancreatitis associated with antipsychotics, and cases were younger men (59%) (mean age, 39 years). Alcohol, diabetes, and previous lithiasis appeared in 27%; polypharmacy was associated with 53% of cases, and 80% had concomitant use of other medication linked to pancreatitis.The median lipase, amylase, and alkaline phosphate during acute presentation were 1210 IU/L (range, 243-5482 IU/L), 492 IU/L (range, 3-2916 IU/L), and 152 IU/L (range, 119-367 IU/L), respectively. Median exposure to antipsychotics were 49 days (range, 5-3,650 days); most were mild (63%, n = 26), several severe (27%, n = 11), and few fatal (10%, n = 4). We identified 41 reports of antipsychotic-related acute pancreatitis, many associated with antipsychotic polypharmacy. Olanzapine, risperidone, quetiapine, aripiprazole, and ziprasidone are associated with acute pancreatitis and often in combination with mood stabilizers.

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

    Directory of Open Access Journals (Sweden)

    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

  17. Application of On-line Electrochemistry/Electrospray/Tandem Mass Spectrometry to a Quantification Method for the Antipsychotic Drug Zotepine in Human Serum

    OpenAIRE

    NOZAKI, Kazuyoshi; OSAKA, Issey; KAWASAKI, Hideya; ARAKAWA, Ryuichi

    2009-01-01

    A simple, rapid, and sensitive on-line liquid chromatographic electrochemistry/electrospray/tandem mass spectrometry (LC-EC/ESI-MS/MS) method for the determination of zotepine in human serum was developed using a new generated-electrochemically fragment ion, and was validated. A recent novel technique of LC-EC/ESI-MS/MS that combines LC-MS/MS and the on-line EC reaction is potentially applicable to developing a quantification method for drugs in biological samples. Newly formed products gener...

  18. Oculomotor and neuropsychological effects of antipsychotic treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    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.

  19. Sensorimotor gating and habituation in antipsychotic-naive, first-episode schizophrenia patients before and after 6 months' treatment with quetiapine

    DEFF Research Database (Denmark)

    Aggernaes, Bodil; Glenthøj, Birte Yding; Ebdrup, Bjorn H

    2010-01-01

    , since these patients are so difficult to recruit. Furthermore, longitudinal studies are few, and their results are inconsistent: some results indicating a reduction of PPI deficits by treatment with atypical antipsychotics, while others do not. This study reports on PPI, habituation and sensitization...... of the human startle reflex in a large group of antipsychotic-naive, first-episode schizophrenia patients, and the effect of subsequent treatment with quetiapine. Thirty-four antipsychotic-naive, first-episode schizophrenia patients (24 males, 10 females), and age- and gender-matched healthy controls were...

  20. Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes.

    Science.gov (United States)

    Stevenson, J M; Reilly, J L; Harris, M S H; Patel, S R; Weiden, P J; Prasad, K M; Badner, J A; Nimgaonkar, V L; Keshavan, M S; Sweeney, J A; Bishop, J R

    2016-02-23

    Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development.

  1. Appropriate prescribing in nursing homes demonstration project (APDP) study protocol: pragmatic, cluster-randomized trial and mixed methods process evaluation of an Ontario policy-maker initiative to improve appropriate prescribing of antipsychotics

    OpenAIRE

    Desveaux, Laura; Gomes, Tara; Tadrous, Mina; Jeffs, Lianne; Taljaard, Monica; Rogers, Jess; Bell, Chaim M.; Ivers, Noah M.

    2016-01-01

    Background Antipsychotic medications are routinely prescribed in nursing homes to address the behavioral and psychological symptoms of dementia. Unfortunately, inappropriate prescribing of antipsychotic medications is common and associated with increased morbidity, adverse drug events, and hospitalizations. Multifaceted interventions can achieve a 12?20?% reduction in antipsychotic prescribing levels in nursing homes. Effective interventions have featured educational outreach and ongoing perf...

  2. Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

    Science.gov (United States)

    Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P; Podea, Delia; Micluția, Ioana; Tiugan, Alexandru; Păcală, Bogdan; Grecu, Iosif Gabos; Noy, Adam; Zamora, Daisy; Davis, John M

    2017-07-01

    Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of

  3. 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

    Drugs acting at dopamine D2-like receptors play a pivotal role in the treatment of both schizophrenia and Parkinson's disease. Recent studies have demonstrated a role for G-protein independent D2 receptor signaling pathways acting through beta-arrestin. In this study we describe the establishment...... of a Bioluminescence Resonance Energy Transfer (BRET) assay for measuring dopamine induced recruitment of human beta-arrestin2 to the human dopamine D2 receptor. Dopamine, as well as the dopamine receptor agonists pramipexole and quinpirole, acted as full agonists in the assay as reflected by their ability to elicit...... marked concentration dependent increases in the BRET signal signifying beta-arrestin2 recruitment to the D2 receptor. As expected from their effect on G-protein coupling and cAMP levels mediated through the D2 receptor RNPA, pergolide, apomorphine, ropinirole, bromocriptine, 3PPP, terguride, aripiprazole...

  4. [Cognition, schizophrenia and the effect of antipsychotics].

    Science.gov (United States)

    Stip, E

    2006-01-01

    In this review, we conclude that cognitive impairments are as important as positive and negative symptoms in the clinical assessment and management of patients with schizophrenia. This is not a comprehensive review, considering that the new Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) model will soon provide valuable data. It is however a product of the collective efforts of a French Canadian clinical research team that proposes a synthesis of data of pragmatic interest to clinicians. Medication with improved safety and cognition profile, gene-rally lead to better outcomes by facilitating compliance with drug regimens and rehabilitation programs. In addition, measures of attention and executive function (EF) appear to improve with novel antipsychotics when compared to traditional neuroleptics. Nevertheless, evaluating cognitive performance is not a routine procedure outside the domain of research. For example, procedural learning (PL) -- an important measure of cognitive function -- refers to cognitive and motor learning processes in which execution strategies cannot be explicitly described (ie learning by doing). These actions or procedures are then progressively learned through trial and error until automation of optimal performance is established. Procedural learning is rarely assessed in clinical practice. Inconsistent findings regarding the effects of neuroleptic drugs on PL have been reported. Trials using acute administration of chlorpromazine in normal subjects induced PL deficits, suggesting the direct effect of neuroleptics, presumably via a D(2) dopamine blockade in the striatum. In a recent study by our group, schizophrenia patients, divided into three groups according to their pharmacological treatment (haloperidol, clozapine and risperidone) were compared to normal controls on two PL tasks; a visuomotor learning task (mirror drawing) and a problem solving learning task (Tower of Toronto). No deficits were detected

  5. Use of antipsychotics increases the risk of fracture: a systematic review and meta-analysis.

    Science.gov (United States)

    Lee, S-H; Hsu, W-T; Lai, C-C; Esmaily-Fard, A; Tsai, Y-W; Chiu, C-C; Wang, J; Chang, S-S; Lee, C C

    2017-04-01

    Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs). The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures. Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis. The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83). FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.

  6. Atypical depression: current perspectives

    Directory of Open Access Journals (Sweden)

    Łojko D

    2017-09-01

    Full Text Available Dorota Łojko,1 Janusz K Rybakowski1,2 1Department of Adult Psychiatry, 2Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland Abstract: The history and present status of the definition, prevalence, neurobiology, and treatment of atypical depression (AD is presented. The concept of AD has evolved through the years, and currently, in Diagnostic and Statistical Manual of Mental Disorders (DSM, Fifth Edition, the specifier of depressive episode with atypical feature is present for both diagnostic groups, that is, depressive disorders and bipolar and related disorders. This specifier includes mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity. Prevalence rates of AD are variable, depending on the criteria, methodology, and settings. The results of epidemiological studies using DSM criteria suggest that 15%–29% of depressed patients have AD, and the results of clinical studies point to a prevalence of 18%–36%. A relationship of AD with bipolar depression, seasonal depression, and obesity has also been postulated. Pathogenic research has been mostly focused on distinguishing AD from melancholic depression. The differences have been found in biochemical studies in the areas of hypothalamic–pituitary–adrenal axis, inflammatory markers, and the leptin system, although the results obtained are frequently controversial. A number of findings concerning such differences have also been obtained using neuroimaging and neurophysiological and neuropsychological methods. An initial concept of AD as a preferentially monoamine oxidase inhibitor-responsive depression, although confirmed in some further studies, is of limited use nowadays. Currently, despite numerous drug trials, there are no comprehensive treatment guidelines for AD. We finalize the article by describing the future research perspectives for the definition, neurobiology, and treatment. A better

  7. Atypical depression: current perspectives

    Science.gov (United States)

    Łojko, Dorota; Rybakowski, Janusz K

    2017-01-01

    The history and present status of the definition, prevalence, neurobiology, and treatment of atypical depression (AD) is presented. The concept of AD has evolved through the years, and currently, in Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, the specifier of depressive episode with atypical feature is present for both diagnostic groups, that is, depressive disorders and bipolar and related disorders. This specifier includes mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity. Prevalence rates of AD are variable, depending on the criteria, methodology, and settings. The results of epidemiological studies using DSM criteria suggest that 15%–29% of depressed patients have AD, and the results of clinical studies point to a prevalence of 18%–36%. A relationship of AD with bipolar depression, seasonal depression, and obesity has also been postulated. Pathogenic research has been mostly focused on distinguishing AD from melancholic depression. The differences have been found in biochemical studies in the areas of hypothalamic–pituitary–adrenal axis, inflammatory markers, and the leptin system, although the results obtained are frequently controversial. A number of findings concerning such differences have also been obtained using neuroimaging and neurophysiological and neuropsychological methods. An initial concept of AD as a preferentially monoamine oxidase inhibitor-responsive depression, although confirmed in some further studies, is of limited use nowadays. Currently, despite numerous drug trials, there are no comprehensive treatment guidelines for AD. We finalize the article by describing the future research perspectives for the definition, neurobiology, and treatment. A better specification of diagnostic criteria and description of clinical picture, a genome-wide association study of AD, and establishing updated treatment recommendations for this clinical phenomenon should be

  8. Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

    Science.gov (United States)

    Rohleder, Cathrin; Müller, Juliane K.; Lange, Bettina; Leweke, F. M.

    2016-01-01

    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 both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being 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. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs 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. PMID:27877130

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

    Directory of Open Access Journals (Sweden)

    Cathrin Rohleder

    2016-11-01

    Full Text Available There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC, cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial had been conducted and demonstrated that cannabidiol exerts antipsychotic properties in acute schizophrenia comparable to the antipsychotic drug amisulpride accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. However, a plethora of mechanisms of action has been suggested, but their potential relevance for the antipsychotic effects of cannabidiol needs still to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

  10. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.

    2011-01-01

    imprecise, partly because QT interval changes are subject to measurement error. In particular, drug-induced T-wave changes (e.g. flattening of the T-wave) may complicate the measurement of the QT interval. Furthermore, the QT interval depends on the heart rate and a corrected QT (QTc) interval is often used...... of the heart, illustrated as a prolongation of the QT interval on a surface ECG. SCD in individuals receiving antipsychotics has an incidence of approximately 15 cases per 10,000 years of drug exposure but the exact association with TdP remains unknown because the diagnosis of TdP is uncertain. Most patients...... manifesting antipsychotic-associated TdP and subsequently SCD have well established risk factors for SCD, i.e. older age, female gender, hypokalaemia and cardiovascular disease. QT interval prolongation is the most widely used surrogate marker for assessing the risk of TdP but it is considered somewhat...

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

    Directory of Open Access Journals (Sweden)

    Montgomery William

    2009-07-01

    Full Text Available Abstract Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314. Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4% who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests, recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a

  12. Subjective Versus Objective Weight Gain During Acute Treatment With Second-Generation Antipsychotics in Schizophrenia and Bipolar Disorder.

    Science.gov (United States)

    Gao, Keming; Fang, Fang; Wang, Zuowei; Calabrese, Joseph R

    2016-12-01

    To compare objective and subjective weight gain of second-generation antipsychotics in schizophrenia and bipolar disorder. English-language literature published and cited in PubMed (MEDLINE) from January 1966 to December 2015 was searched with the keywords antipsychotic, atypical antipsychotic, or generic/brand name of atypical antipsychotics, and schizophrenia, bipolar disorder, bipolar mania, or bipolar depression, and safety, tolerability, weight gain, and randomized, placebo-controlled clinical trials. The absolute risk increases and the numbers needed to treat to harm (NNH) for ≥7% weight gain (objective) and self-report weight gain (subjective) were estimated. In schizophrenia, the NNH for 7% or greater weight gain ranged from 5 to 62, and the NNH for self-reported weight gain was from 11 to -224. The ratio of self-reported NNH to 7% or greater NNH was from 1.5 to 8.0. In bipolar mania, the NNH for 7% or greater weight gain ranged from 7 to -101 and the NNH for self-reported weight gain was from 13 to 84. The ratio of self-reported NNH to 7% or greater NNH was from 0.9 to 2.5. In bipolar depression, the NNH for 7% or greater weight gain ranged from 5 to 69, and the NNH for self-reported weight gain was from 8 to 17. The ratio of self-reported NNH to 7% or greater NNH was 1.2 to 1.6. Subjective reporting underestimated the risk of antipsychotic-related weight gain compared with objectively measured weight change. Self-awareness of antipsychotic-related weight gain was lower in patients with schizophrenia than in patients with bipolar disorder. Measuring weight change during antipsychotic treatment should be a routine practice.

  13. 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

    2016-12-28

    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 730th 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 <80% of the days (aPR = 1.49; 95%IC = 1.28-1.74). This first exploration of community pharmacy 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

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

    Directory of Open Access Journals (Sweden)

    Rayees Ahmad Wani

    2015-01-01

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

  15. Prolactin gene polymorphism (-1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics

    NARCIS (Netherlands)

    Ivanova, Svetlana A.; Osmanova, Diana Z.; Boiko, Anastasia S.; Pozhidaev, Ivan V.; Freidin, Maxim B.; Fedorenko, Olga Yu.; Semke, Arkadiy V.; Bokhan, Nikolay A.; Kornetova, Elena G.; Rakhmazova, Lubov D.; Wilffert, Bob; Loonen, Anton J. M.

    Background: Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin

  16. 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 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.

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

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

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

  18. Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study.

    Science.gov (United States)

    Koga, Arthur T; Strauss, John; Zai, Clement; Remington, Gary; De Luca, Vincenzo

    2016-03-01

    In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication.

  19. Time course of the attenuation effect of repeated antipsychotic treatment on prepulse inhibition disruption induced by repeated phencyclidine treatment

    Science.gov (United States)

    Li, Ming; He, Erik; Volf, Nick

    2011-01-01

    Antagonism of prepulse inhibition (PPI) deficits produced by psychotomimetic drugs has been widely used as an effective tool for the study of the mechanisms of antipsychotic action and identifying potential antipsychotic drugs. Many studies have relied on the acute effect of a single administration of antipsychotics, whereas patients with schizophrenia are treated chronically with antipsychotic drugs. The clinical relevance of acute antipsychotic effect in this model is still an open question. In this study, we investigated the time course of repeated antipsychotic treatment on persistent PPI deficit induced by repeated phencyclidine (PCP) treatment. After a baseline test with saline, male Sprague-Dawley rats were repeatedly injected with either vehicle, haloperidol (0.05 mg/kg), clozapine (5.0 or 10.0 mg/kg), olanzapine (2.0 mg/kg), risperidone (1.0 mg/kg) or quetiapine (10 mg/kg), followed by PCP (1.5 mg/kg, sc) and tested for PPI once daily for 6 consecutive days. A single injection of PCP disrupted PPI and this effect was maintained with repeated PCP injections throughout the testing period. Acute clozapine, but not other antipsychotic drugs, attenuated acute PCP-induced PPI disruption at both tested doses. With repeated treatment, clozapine and quetiapine maintained their attenuation, while risperidone enhanced its effect with a significant reduction of PCP-induced disruption toward the end of treatment period. In contrast, repeated haloperidol and olanzapine treatments were ineffective. The PPI effects of these drugs were more conspicuous at a higher prepulse level (e.g. 82 dB) and were dissociable from their effects on startle response and general activity. Overall, the repeated PCP-PPI model appears to be a useful model for the study of the time-dependent antipsychotic effect, and may help identify potential treatments that have a quicker onset of action than current antipsychotics. PMID:21402097

  20. Costs, Control or Just Good Clinical Practice? The Use of Antipsychotic Medications and Formulary Decision-Making in Large U.S. Prisons and Jails

    Science.gov (United States)

    Veysey, Bonita M.; Stenius, Vanja; Mazade, Noel; Schacht, Lucille

    2007-01-01

    Medications are central to the psychiatric armamentorium in U.S. jails and prisons. Psychiatric medications are used both to stabilize acute symptoms as well as maintain mental health once symptoms are reduced. Both jails and prisons rely heavily on traditional antipsychotics, but both have a full array of atypical medications in their…

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

    Science.gov (United States)

    Tesfaye, Siranesh; Debencho, Nigussie; Kisi, Teresa; Tareke, Minale

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Siranesh Tesfaye

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

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

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

    Science.gov (United States)

    2012-01-01

    Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009) from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%), followed by valproic acid (23%), mirtazapine and venlafaxine (16% each), quetiapine (15%), lamotrigine (14%) and olanzapine (13%). Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI), but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined) was the most frequently prescribed drug (39%); aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine) with mood stabilizers (lithium, valproic acid, lamotrigine) and / or atypical antipsychotics (quetiapine, olanzapine) are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines. PMID:22998655

  5. Could cannabidiol be used as an alternative to antipsychotics?

    Science.gov (United States)

    Fakhoury, Marc

    2016-09-01

    Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Antipsychotic treatment among youth in foster care.

    Science.gov (United States)

    Dosreis, Susan; Yoon, Yesel; Rubin, David M; Riddle, Mark A; Noll, Elizabeth; Rothbard, Aileen

    2011-12-01

    Despite national concerns over high rates of antipsychotic medication use among youth in foster care, concomitant antipsychotic use has not been examined. In this study, concomitant antipsychotic use among Medicaid-enrolled youth in foster care was compared with disabled or low-income Medicaid-enrolled youth. The sample included 16 969 youths younger than 20 years who were continuously enrolled in a Mid-Atlantic state Medicaid program and had ≥1 claim with a psychiatric diagnosis and ≥1 antipsychotic claim in 2003. Antipsychotic treatment was characterized by days of any use and concomitant use with ≥2 overlapping antipsychotics for >30 days. Medicaid program categories were foster care, disabled (Supplemental Security Income), and Temporary Assistance for Needy Families (TANF). Multicategory involvement for youths in foster care was classified as foster care/Supplemental Security Income, foster care/TANF, and foster care/adoption. We used multivariate analyses, adjusting for demographics, psychiatric comorbidities, and other psychotropic use, to assess associations between Medicaid program category and concomitant antipsychotic use. Average antipsychotic use ranged from 222 ± 110 days in foster care to only 135 ± 101 days in TANF (P foster care only and 24% in foster care/adoption compared with foster care system.

  7. Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat

    OpenAIRE

    Davey, K J; Cotter, P D; O?Sullivan, O.; Crispie, F; Dinan, T G; Cryan, J F; O'Mahony, S M

    2013-01-01

    The atypical antipsychotic olanzapine is often associated with serious metabolic side effects including weight gain and increased visceral fat. These adverse events are a considerable clinical problem and the mechanisms underlying them are multifactorial and poorly understood. Growing evidence suggests that the gut microbiota has a key role in energy regulation and disease states such as obesity. Moreover, we recently showed that chronic olanzapine altered the composition of the gut microbiom...

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

    Directory of Open Access Journals (Sweden)

    Elke Ericson

    2008-08-01

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

  9. Antipsychotics, mood stabilisers, and risk of violent crime.

    Science.gov (United States)

    Fazel, Seena; Zetterqvist, Johan; Larsson, Henrik; Långström, Niklas; Lichtenstein, Paul

    2014-09-27

    Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden. We used linked Swedish national registers to study 82,647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006-09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register. In 2006-09, 40,937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41,710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47-0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62-0·93). However, we identified potentially important differences by diagnosis-mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

    To determine the effectiveness and security of the antipsychotics available for the management of adult patients with schizophrenia in the maintenance phase. To develop recommendations of treatment for the maintenance phase of the disease. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. 18 studies were included to evaluate the effectiveness and / or safety of different antipsychotic drugs first and second generation. Overall, antipsychotics (AP) showed superiority over placebo in relapse rate over 12 months (RR 0.59 95% CI 0.42, 0.82) and hospitalization rate over 24 months of follow-up (RR 0.38 95% 0.27, 0.55); its use is associated with increased risk of treatment dropout (RR 0.53 95% CI 0.46, 0.61) and adverse events such as weight gain, dystonia, extrapyramidal symptoms and sedation. There was no difference in the outcome of re hospitalizations, comparisons on quality of life, negative symptoms or weight gain between AP first and second generation. Continuous or standard dose regimens appear to be superior to intermittent or low doses in reducing the risk of abandonment of treatment regimes. Adult patients diagnosed with schizophrenia should receive maintenance treatment with antipsychotics. The medication of choice will depend on the management of the acute phase, the patient's tolerance to it and the presentation of adverse events. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  12. Anti-Inflammatory properties of antipsychotics via microglia modulations: are antipsychotics a 'fire extinguisher' in the brain of schizophrenia?

    Science.gov (United States)

    Kato, T A; Monji, A; Mizoguchi, Y; Hashioka, S; Horikawa, H; Seki, Y; Kasai, M; Utsumi, H; Kanba, S

    2011-06-01

    Schizophrenia is one of the most severe psychiatric diseases noted for its chronic and often debilitating processes; affecting approximately 1% of the world's population, while its etiology and therapeutic strategies still remain elusive. In the 1950s, the discovery of antipsychotic effects of haloperidol and chlorpromazine shifted the paradigm of schizophrenia. These drugs proved to be antagonists of dopamine D2 receptor (D2R), thus dopamine system dysfunction came to be hypothesized in the pathophysiology of schizophrenia, and D2R antagonism against dopamine neurons has been considered as the primary therapeutic target for schizophrenia. In addition, abnormalities of glutamatergic neurons have been indicated in the pathophysiology of schizophrenia. On the other hand, recent neuroimaging studies have shown that not only dementia but also schizophrenic patients have a significant volume reduction of some specific regions in the brain, which indicates that schizophrenia may involve some neurodegenerative process. Microglia, major sources of various inflammatory cytokines and free radicals such as superoxide and nitric oxide (NO) in the CNS, play a crucial role in a variety of neurodegenerative diseases such as dementia. Recent postmortem and positron emission computed tomography (PET) studies have indicated that activated microglia may be present in schizophrenic patients. Recent in vitro studies have suggested the anti-inflammatory effects of antipsychotics on microglial activation. In this article, we review the anti-inflammatory effects of antipsychotics on microglia, and propose a novel therapeutic hypothesis of schizophrenia from the perspective of microglial modulation.

  13. Neuroleptic malignant syndrome induced by atypical neuroleptics and responsive to lorazepam

    OpenAIRE

    Yacoub, Adeeb; Francis, Andrew

    2006-01-01

    Objective The authors report three cases of neuroleptic malignant syndrome (NMS) induced by atypical antipsychotics (olanzapine and clozapine) which showed classic features of NMS including muscular rigidity and prominent fever. Method Case reports. Results A 66-year-old man with dementia and alcohol abuse developed NMS while on olanzapine for agitation and combativeness. A 62-year-old man with schizophrenia developed NMS 6 days after starting clozapine. A 43-year-old man with bipolar disorde...

  14. Does the use of antipsychotics increase when coercion decreases in a general psychiatric ward?

    DEFF Research Database (Denmark)

    Højlund, Mikkel; Høgh, Lene; Munk-Jørgensen, Povl

    2017-01-01

    %), risperidone (18%) and clozapine (15%). In exible dosing the most frequently used antipsychotic drug was also quetiapine (50%) followed by olanzapine (27%) and chlorprothixene (17%). Conclusions Reduction in coercive measures at the Department of Psychiatry in Aabenraa has not lead to an increase...

  15. Antipsychotic use in a resource-limited setting: Findings in an ...

    African Journals Online (AJOL)

    Method: The study is a cross-sectional survey conducted as a retrospective chart review at a psychiatric hospital in the Eastern Cape over a study period of 2 months. The demographics, diagnostic data, antipsychotic drug used and whether a switch from an FGA to an SGA took place were recorded using a data collection ...

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

    Directory of Open Access Journals (Sweden)

    Dayabandara M

    2017-08-01

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

  17. "First do no harm." A systematic review of the prevalence and management of antipsychotic adverse effects.

    Science.gov (United States)

    Young, Su Ling; Taylor, Mark; Lawrie, Stephen M

    2015-04-01

    We aim to identify the prevalence and management strategies of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects. Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence or management of adverse antipsychotic effects is a neglected area. A systematic review was undertaken using pre-defined search criteria and three databases, with hand searching of citations and references. Inclusion was agreed on by two independent researchers after review of abstracts or full text. Quality analysis of included studies was conducted using pre-agreed criteria. In total, 53 studies met inclusion criteria, revealing the following: (1) antipsychotic polypharmacy was associated with increased frequency of adverse effects, and (2) a longer duration of treatment is associated with greater severity (e.g. higher BMI); (3) clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; (4) hyperprolactinaemia was more common in women than men, but 50% men noted sexual dysfunction versus 25-50% in women; (5) despite clinical guideline recommendations there is a low rate of baseline testing for lipids and glucose; and (6) seven studies described adverse effect management strategies, but only two examined their efficacy - one found a significant reduction in weight with non-pharmacological group therapy and the other found a significant reduction in dyslipidaemia with statins. Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed

  18. Psychosis patients' knowledge, adherence and attitudes towards the naming of antipsychotic medication in Hong Kong.

    Science.gov (United States)

    Lau, Karen Chi-Kwan; Lee, Edwin Ho-Ming; Hui, Christy Lai-Ming; Chang, Wing-Chung; Chan, Sherry Kit-Wa; Chen, Eric Yu-Hai

    2015-10-01

    Non-adherence to medication is a common and significant challenge to successful treatment of psychosis. Knowledge of prescribed antipsychotic medication may influence psychosis patients' willingness to adhere to prescriptions. This study aimed to assess knowledge of psychosis patients on their prescribed antipsychotic medication with regard to drug name, type, dosage, purpose, side effects and reasons for taking medication, so as to investigate the associations between knowledge and adherence. The study also aimed to evaluate patient attitudes towards the current Chinese name of 'anti-psyche drug' for antipsychotic medication in Hong Kong, and survey patients' opinions on alternative names for antipsychotic medication. A questionnaire was administered to 70 consecutive patients from the psychiatric ward and outpatient clinic at Queen Mary Hospital in Hong Kong. Current knowledge of Hong Kong psychosis patients falls short in areas of drug name (51.4% unaware), drug type (40% unaware) and prescribed dosage (28.6% unaware). The rate of self-reported non-adherence in the study sample was 38.6%. Adherence to medication was found to be positively associated with knowledge of purpose for taking medication. The current Chinese name 'anti-psyche drug' had a rating of 47/100 among psychosis patients. Measures should be taken to improve patient knowledge in areas of drug name, type and prescribed dosage. Reminding patients about the purpose of medication may also benefit adherence and overall treatment. Finally, because of the possible stigma of the current name of antipsychotic medication, an alternative term may be more favourable in promoting its acceptance in Hong Kong. © 2014 Wiley Publishing Asia Pty Ltd.

  19. Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian

    2017-01-01

    to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population...... between 1995 and 2010 in the Danish Prescription Register and compared the prevalence and incidence of use of antidepressants, sedatives and antipsychotics. The prevalence of antidepressant use by women was lower in 1998 but no different from that in controls in 2003 and 2008; the prevalence...... of antidepressant use by men was higher in both 1998 and 2008 than in the Danish population. The incidence of antidepressant use was lower for female members in 1996–2000, but no difference was observed in the other periods. The prevalence and incidence of use of sedatives and antipsychotics did not consistently...

  20. Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role of heat-shock protein production.

    Science.gov (United States)

    Kaneta, Hiroo; Ukai, Wataru; Tsujino, Hanako; Furuse, Kengo; Kigawa, Yoshiyasu; Tayama, Masaya; Ishii, Takao; Hashimoto, Eri; Kawanishi, Chiaki

    2017-09-01

    Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801. We herein demonstrated that antipsychotics promoted or restored changes in the oligodendrocyte/GABAergic interneuron differentiation functions of NG2(+) cells induced by the exposure to MK-801, which was considered to be one of the drug-induced schizophrenia model. We also demonstrated that antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with differentiation impairment. The antipsychotics olanzapine, aripiprazole, and blonanserin, but not haloperidol increased HSP90 levels, which were reduced by the exposure to MK-801. Our results showed that antipsychotics, particularly those recently synthesized, exerted similar GABAergic interneuron genesis effects on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing cellular HSP production, and also suggest that HSP90 may play a crucial role in the pathophysiology of schizophrenia and is a key target for next drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Metabolic syndrome: relative risk associated with post-traumatic stress disorder (PTSD) severity and antipsychotic medication use.

    Science.gov (United States)

    Heppner, Pia S; Lohr, James B; Kash, Taylor P; Jin, Hua; Wang, Hongjun; Baker, Dewleen G

    2012-01-01

    In recent years, numerous lines of converging evidence have revealed an association between post-traumatic stress disorder (PTSD) and impaired physical health outcomes, including cardiovascular disease and metabolic syndrome. Although these findings have been interpreted as indicating a direct association of PTSD with metabolic syndrome and obesity, previous studies have not addressed the important confound of antipsychotic drug usage in this population. Second generation antipsychotic medications themselves are associated with metabolic syndrome and obesity, and it is unclear whether the common utilization of these drugs in PTSD may account for some if not all of the observed metabolic problems. The present study examined the relative contributions of PTSD severity and use of antipsychotic medications to risk of metabolic syndrome among veterans. Cross-sectional clinical data, including five factors representing metabolic syndrome, psychiatric diagnoses, and medications were gathered from 253 veterans enrolling in mental health services. We used a logistic regression model to measure the relative association of antipsychotic medication use and PTSD severity on risk of metabolic syndrome. We found that antipsychotic medication usage was not uniquely associated with elevated risk of metabolic syndrome (Wald = 0.30, ns) when PTSD severity and other sociodemographic, psychiatric, and behavioral variables were accounted for. Furthermore, PTSD severity continued to be a significant and unique predictor of risk for metabolic syndrome (Wald = 4.04, p PTSD, independent of antipsychotic medications, is associated with increased risk of metabolic syndrome. Published by Elsevier Inc.

  2. Atypical swallowing: a review.

    Science.gov (United States)

    Maspero, C; Prevedello, C; Giannini, L; Galbiati, G; Farronato, G

    2014-06-01

    Atypical swallowing is a myofunctional problem consisting of an altered tongue position during the act of swallowing. High incidence in population, multifactorial etiology and the recurring connection with the presence of malocclusions made it a topic of strong interest and discussion in science. The purpose of this review is to illustrate the current orientation on the topic of atypical swallowing, trying in particular to answer two questions: 1) what kind of connection is there between atypical swallowing and malocclusion; 2) what kind of therapy should be used to solve it. This review was conducted on the Medline database [www.ncbi.nim.nih.gov/pubmed] searching for the keywords "atypical swallowing" and "tongue thrust". We examined all the documents from the year 1990 onwards, excluding the ones about syndromic cases of the central motor system. The causal relation between the two problems seems to be biunique: some authors affirm that this oral habit starts as a compensation mechanism for a preexisting malocclusion (especially in case of open-bite); other texts show that it has a tendency to exacerbate cases of malocclusion; it is also proven that a non-physiological tongue thrust can negatively influence the progress of an ongoing orthodontic therapy. Thereby, the best therapeutic approach seems to be a multidisciplinary one: beside orthodontics, which is necessary to correct the malocclusion, it is essential to set up a myofunctional rehabilitation procedure to correct the oral habit, therefore granting long time permanent results. There is also proof of a substantial difference between the results obtained from early (deciduous or primary mixed dentition) or later treatments. The biunique causal relation between atypical swallowing and malocclusion suggests a multidisciplinary therapeutic approach, orthodontic and myofunctional, to temporarily solve both problems. An early diagnosis and a prompt intervention have a significantly positive influence on the

  3. Modulation of antipsychotic-induced extrapyramidal side effects by medications for mood disorders.

    Science.gov (United States)

    Tatara, Ayaka; Shimizu, Saki; Shin, Noriyuki; Sato, Maho; Sugiuchi, Tomone; Imaki, Junta; Ohno, Yukihiro

    2012-08-07

    Antipsychotic drugs are widely used not only for schizophrenia, but also for mood disorders such as bipolar disorder and depression. To evaluate the interactions between antipsychotics and drugs for mood disorders in modulating extrapyramidal side effects (EPS), we examined the effects of antidepressants and mood-stabilizing drugs on haloperidol (HAL)-induced bradykinesia and catalepsy in mice and rats. The selective serotonin reuptake inhibitors (SSRIs), fluoxetine and paroxetine, and the tricyclic antidepressant (TCA) clomipramine, which showed no EPS by themselves, significantly potentiated HAL-induced bradykinesia and catalepsy in a dose-dependent manner. In contrast, the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine failed to augment, but rather attenuated HAL-induced bradykinesia and catalepsy. Mianserin also tended to reduce the EPS induction. In addition, neither treatment with lithium, sodium valproate nor carbamazepine potentiated HAL-induced EPS. Furthermore, treatment of animals with ritanserin (5-HT2A/2C antagonist), ondansetron (5-HT3 antagonist), and SB-258585 (5-HT6 antagonist) significantly antagonized the EPS augmentation by fluoxetine. Intrastriatal injection of ritanserin or SB-258585, but not ondansetron, also attenuated the EPS induction. The present study suggests that NaSSAs are superior to SSRIs or TCAs in combined therapy for mood disorders with antipsychotics in terms of EPS induction. In addition, 5-HT2A/2C, 5-HT3 and 5-HT6 receptors seem to be responsible for the augmentation of antipsychotic-induced EPS by serotonin reuptake inhibitors. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Hypothermia due to Antipsychotic Medication: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Cherryl Zonnenberg

    2017-09-01

    Full Text Available BackgroundHypothermia is a rare, but potentially fatal adverse effect of antipsychotic drug (APD use. Although the opposite condition, hyperthermia, has been researched extensively in the context of the malignant antipsychotic syndrome, little is known about hypothermia due to APDs.ObjectiveThis study aimed to review the literature on hypothermia in the context of APD use, and formulate implications for research and clinical care.MethodsA systematic search was made in PubMed and Ovid Medline.ResultsThe literature search yielded 433 articles, including 57 original case descriptions of hypothermia developed during APD use with non-toxic plasma levels. All cases together indicate that the risk of developing hypothermia is highest during the 7 days following initiation, or increase in dosage, of APDs, especially in the presence of additional predisposing factors, such as advanced age, exposure to cold, adjuvant use of benzodiazepines, and (subclinical hypothyroidism. In addition, data derived from drug-monitoring agencies suggest that the prevalence of APD-related hypothermia is at least 10 times higher than suggested by the literature.ConclusionWe conclude that health-care professionals need to monitor the body temperature of patients starting with (an increased dose of APDs for a duration of 7–10 days to prevent hypothermia, especially in the presence of multiple risk factors. Moreover, systematic studies are needed to establish the actual prevalence of APD-related hypothermia as well as the relative risk for individual APDs.

  5. Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

    Directory of Open Access Journals (Sweden)

    Kyle J. Burghardt

    2013-01-01

    Full Text Available Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1 and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226 or bipolar disorder (n=94 were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

  6. Cognitive Functioning in Euthymic Bipolar Patients on Monotherapy with Novel Antipsychotics or Mood Stabilizers.

    Science.gov (United States)

    Şentürk Cankorur, Vesile; Demirel, Hilal; Atbaşoğlu, Cem

    2017-09-01

    Bipolar disorder is associated with cognitive dysfunction in several domains. Medication effect is a potential confounder that can only be statistically controlled in many studies. The cognitive profile in bipolar disorder during remission on maintenance antipsychotics or mood stabilizers medication has not been compared before. We compared the cognitive profile of bipolar disorder patients euthymic for 2 month or more on monotherapy with novel antipsychotics (AP) (n=16), lithium carbonate (Li) (n=25) or valproic acid (VPA; n=26). Forty-two individuals were assessed as controls. The cognitive battery included Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Wechsler Memory Scale (WMS), and Wisconsin Card Sorting Test (WCST). All three patient groups compared to controls performed poorly on the working memory and verbal memory tasks (F=3.59, df=3, p=0.02 for WAIS-R Arithmetic and F=123.64, df=3, pbipolar patients on monotherapy with atypical AP, whereas verbal memory impairment might be related to bipolar disorder itself. Working memory might be a state marker, whereas verbal memory could be a trait marker of bipolar disorder. Atypical AP might have an adverse effect on cognition in bipolar disorder. These findings cannot be generalized to all bipolar patients, particularly the poor responders to monotherapy.

  7. Presynaptic Dopamine Synthesis Capacity in Schizophrenia and Striatal Blood Flow Change During Antipsychotic Treatment and Medication-Free Conditions.

    Science.gov (United States)

    Eisenberg, Daniel Paul; Yankowitz, Lisa; Ianni, Angela M; Rubinstein, Dani Y; Kohn, Philip D; Hegarty, Catherine E; Gregory, Michael D; Apud, José A; Berman, Karen F

    2017-10-01

    Standard-of-care biological treatment of schizophrenia remains dependent upon antipsychotic medications, which demonstrate D 2 receptor affinity and elicit variable, partial clinical responses via neural mechanisms that are not entirely understood. In the striatum, where D 2 receptors are abundant, antipsychotic medications may affect neural function in studies of animals, healthy volunteers, and patients, yet the relevance of this to pharmacotherapeutic actions remains unresolved. In this same brain region, some individuals with schizophrenia may demonstrate phenotypes consistent with exaggerated dopaminergic signaling, including alterations in dopamine synthesis capacity; however, the hypothesis that dopamine system characteristics underlie variance in medication-induced regional blood flow changes has not been directly tested. We therefore studied a cohort of 30 individuals with schizophrenia using longitudinal, multi-session [ 15 O]-water and [ 18 F]-FDOPA positron emission tomography to determine striatal blood flow during active atypical antipsychotic medication treatment and after at least 3 weeks of placebo treatment, along with presynaptic dopamine synthesis capacity (ie, DOPA decarboxylase activity). Regional striatal blood flow was significantly higher during active treatment than during the placebo condition. Furthermore, medication-related increases in ventral striatal blood flow were associated with more robust amelioration of excited factor symptoms during active medication and with higher dopamine synthesis capacity. These data indicate that atypical medications enact measureable physiological alterations in limbic striatal circuitry that vary as a function of dopaminergic tone and may have relevance to aspects of therapeutic responses.

  8. Sobrepeso e obesidade em pacientes esquizofrênicos em uso de clozapina comparado com o uso de outros antipsicóticos Overweight and obesity in schizophrenic patients taking clozapine compared to the use of other antipsychotics

    Directory of Open Access Journals (Sweden)

    Carmen Lúcia Leitão-Azevedo

    2006-08-01

    Full Text Available INTRODUÇÃO: O uso de antipsicóticos tem sido fundamental no tratamento de portadores de esquizofrenia. Entretanto, tanto a clozapina quanto a maior parte dos antipsicóticos atípicos podem induzir um maior ganho de peso corporal e alterações metabólicas. OBJETIVO: Comparar a freqüência de sobrepeso e obesidade em pacientes esquizofrênicos expostos à clozapina com a dos expostos a demais antipsicóticos. MÉTODO: Foram estudados 121 pacientes esquizofrênicos, com idade de 18 anos ou mais, de ambos os sexos, atendidos no Ambulatório de Esquizofrenia e Demências do Hospital de Clínicas de Porto Alegre, encaminhados de forma consecutiva. Foram avaliadas medidas antropométricas de 53 pacientes em uso de clozapina e de 68 usando outros antipsicóticos, e todos preencheram os critérios diagnósticos de esquizofrenia do DSM-IV e CID-10. RESULTADOS: Não houve diferença significativa na freqüência do IMC entre os esquizofrênicos em uso de clozapina, quando comparado com o dos que usam os demais antipsicóticos. As análises mostraram uma elevada prevalência de pacientes (72,7% com excesso de peso (sobrepeso + obesidade. DISCUSSÃO: Devido à maior freqüência de excesso de peso na população esquizofrênica, pode-se evidenciar na amostra um indicativo de maior risco para transtornos vasculares e metabólicos. A ausência de diferença significativa em relação ao uso de clozapina, comparada com os demais antipsicóticos, demonstra a necessidade da montagem de estudos prospectivos determinando a magnitude de ganho de peso e o aumento de risco relativo à exposição específica de cada antipsicótico.BACKGROUND: The use of antipsychotics has been crucial in the treatment of schizophrenic patients. However, clozapine, as well as most atypical antipsychotics, may lead to higher weight gain and metabolic changes. OBJECTIVE: To compare the frequency of overweight and obesity between schizophrenic patients exposed to clozapine to the

  9. 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...

  10. Study on the prescribing patterns of antipsychotic medication in a rural England Community Mental Health Team.

    Science.gov (United States)

    Seshadri, Madhavan; Elsemary, Ahmed; Thalitaya, Madhusudan Deepak; Chikodzore, Lawrence; Nagalingam, Priya

    2017-09-01

    utilized to help the orderly collection of information as dose, patient diagnoses, comorbid substance use etc. SPC was relied upon for investigating the licensing of the different antipsychotics. It was found that the most commonly prescribed antipsychotic was Quetiapine (28.07%) followed by Olanzapine (24.56%), Aripiprazole (14.04%) and Depot drugs (12.28%). It was found that the most commonly used depot drugs were Modecate and Depixol. It was also found that 14% of our patients were prescribed two antipsychotics at the same time. Unlicensed antipsychotics made up 17.54% of all prescribed antipsychotics. It was also found that no documentation on the system evidenced that patients were told about the use of unlicensed antipsychotics. Quetiapine and olanzapine made up 60 % of the unlicensed antipsychotics followed by risperidone and aripiprazole 40%. The conditions that were found to be given unlicensed medications were anxiety neurotic and stress related disorders and somatoform disorders (F40-48), disorders of adult personality and behaviour (F60-F69) and multiple conditions. The most common daily doses prescribed for Aripiprazole were found to be 5, 10 and 15 mg doses. For Quetiapine, it was the 300mg dose and for Olanzapine it was found to be the 10mg dose. In all but one patient antipsychotics were prescribed within BNF limits. One patient was prescribed Olanzapine 25 mg (BNF maximum dose 20 mg). Polypharmacy was found to be used more in the multiple diagnosis and schizophrenia conditions. Patients with schizophrenia and adult personality disorders were found to be the most patients who abused alcohol, cannabis and prescription opioid analgesic medications. Antipsychotics have a range of central nervous system effects and there are situations where it becomes necessary to use them off-license. However, it is essential to explain to the patient about the unlicensed use of antipsychotics and document this on the system. The effects of unlicensed antipsychotics need to

  11. Atypical femoral fractures

    OpenAIRE

    Giannini, Sandro; Chiarello, Eugenio; Tedesco, Giuseppe; Cadossi, Matteo; Luciani, Deianira; Mazzotti, Antonio; Donati, Davide Maria

    2013-01-01

    Bisphosphonates (BPs) represent the most widely used therapy for osteoporosis. Recently, a relationship between long-term treatment with BPs and a subset of atypical femoral fractures (AFFs) from below the lesser trochanter to the sovracondilar line has been described. Many etiopathogenetic theories have been invoked to explain AFFs: reduced bone turnover and increased osteoblast bone apposition with accumulation of microdamage and decreased bone toughness with subsequent increased risk of mi...

  12. Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

    DEFF Research Database (Denmark)

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

    2014-01-01

    INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative...... for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments when compared in a network meta-analysis. Unlike a contrast-based (standard) meta-analysis approach, an arm-based network meta-analysis enables statistical inference from combining...... perform data abstraction and assess risk of bias of eligible trials. We will conduct meta-analyses to establish the effect of all reported therapies on patient-relevant efficacy and safety outcomes when possible. ETHICS AND DISSEMINATION: No formal ethical procedures regarding informed consent...

  13. Osteoporosis Associated with Antipsychotic Treatment in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Haishan Wu

    2013-01-01

    Full Text Available Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis.

  14. 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

    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 of antipsyc...... 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.......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...... of antipsychotic medication in children and adolescents below 19 years of age in Denmark. A national cross-sectional survey registered the use of antipsychotic drugs on a given date. A questionnaire was sent to all child and adolescent psychiatric departments and all consultants in child and adolescent psychiatry...

  15. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

    with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...

  16. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agnoist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study - the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

    with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Materials and methods: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs...

  17. Use of Depot Antipsychotic Medications for Medication Nonadherence in Schizophrenia

    OpenAIRE

    West, Joyce C.; Marcus, Steven C.; Wilk, Joshua; Countis, Lisa M.; Regier, Darrel A.; Olfson, Mark

    2007-01-01

    Objectives: To describe factors associated with initiation of depot antipsychotic medications in psychiatric outpatients with schizophrenia and recent medication nonadherence. Methods: A national sample of psychiatrists reported on adult outpatients with schizophrenia who were nonadherent with oral antipsychotic medications in the last year. Results: In total, 17.6% of psychiatrists initiated depot antipsychotic injections. Initiation was significantly and positively associated with public in...

  18. Mediators of First- Versus Second-generation Antipsychotic-related Mortality in Older Adults.

    Science.gov (United States)

    Jackson, John W; VanderWeele, Tyler J; Blacker, Deborah; Schneeweiss, Sebastian

    2015-09-01

    Observational studies of older adults showed higher mortality for first-generation antipsychotics than their second- generation counterparts, which led to US Food and Drug Administration warnings, but the actual mechanisms involved remain unclear. A cohort of 9,060 initiators of first-generation antipsychotics and 17,137 of second-generation antipsychotics enrolled in New Jersey and Pennsylvania Medicare were followed for 180 days. Medical events were assessed using diagnostic and procedure codes on inpatient billing claims. For the individual and joint set of medical events (mediators), we estimated the total, direct, and indirect effects of antipsychotic type (first versus second generation) on mortality on the risk ratio scale and the proportion mediated on the risk difference scale, obtaining 95% confidence intervals through bootstrapping. We performed bias analyses for false-negative mediator misclassification in claims data, with sensitivity ranging from 0.25 to 0.75. There were 3,199 deaths (outcomes), 862 cardiovascular events, 675 infectious events, and 491 hip fractures (potential mediators). Mortality was higher for first- than second-generation antipsychotic initiators (adjusted risk ratio: 1.14; 95% confidence interval: 1.06, 1.22). In naïve analyses, that ignored potential misclassification, less than 4% of this difference was explained by any particular medical event. In bias analyses, the proportion mediated ranged from 6% to 16% for stroke, 3% to 9% for ventricular arrhythmia, 3% to 11% for myocardial infarction, 0% venous thromboembolism, 3% to 9% for pneumonia, 0% to 1% for other bacterial infection, and 1% to 3% for hip fracture. Acute cardiovascular events and pneumonia may explain part of the mortality difference between first- and second-generation antipsychotic initiators in this analysis.

  19. Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Douglas L Noordsy

    2010-07-01

    Full Text Available Douglas L Noordsy1, Glenn A Phillips2, Daniel E Ball2, Walter T Linde-Zwirble31Department of Psychiatry, Dartmouth Medical School, Lebanon, NH, USA; 2Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 3ZD Associates, Perkasie, PA, USAObjective: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to ­different treatments.Methods: Adults with schizophrenia in the California Medicaid (MediCal database who ­initiated treatment with index medications in 1998–2001, were classified as having: 1 ­abandoned antipsychotic medications; 2 switched to another medication; or 3 continued with the index antipsychotic, for up to 6 months after the index date.Results: Of 2300 patients meeting eligibility criteria, 1382 (60.1% continued index medications, 480 (20.9% switched, and 438 (19.0% abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications. These included using psychiatric (24.2% vs 14.5%; P < 0.001 or nonpsychiatric (31.5% vs 24.3%; P < 0.05 emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05; making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05 or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05; and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001 or nonpsychiatric (82.7% vs 74.6%; P < 0.001 services.Conclusions: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment.Keywords: antipsychotics, drug therapy, resource use, treatment adherence

  20. Average Out-of-Pocket Expenses Across Different Drug Categories and Commercial Third-Party Payers.

    Science.gov (United States)

    Lenderts, Susan; Kalali, Amir H

    2010-10-01

    In this Trend Watch, we look at retail pharmacy prescriptions for branded and generic attention deficit hyperactivity disorder treatments, atypical antipsychotics, selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors and analyze the average out-of-pocket costs incurred by patients who are covered by commercial third-party prescription plans (i.e., as opposed to patients covered by Medicaid or patients with no prescription coverage). Overall, patient out-of-pocket costs in commercial third-party plans are lower for generic prescriptions than they are for brand prescriptions by at least $19.02. Comparisons across the drug classes reveal that the average co-pay for brands and generics, as well as the difference between brand and generic out-of-pocket costs, differ by drug category.

  1. [Definition of the antineurotic, antipsychotic, neuroplegic and neuroleptic properties of psychotropic substances used in anesthesia and resuscitation].

    Science.gov (United States)

    Deligné, P

    1976-01-01

    There is a great deal of evidences (pharmacological, experimental and clinical, therapeutic, biological, biochemical, metabolic, toxicological and neurophysiological) which permits one to characterise among the psychotropic substances, the antineurotic or antipsychotic properties of certain psycholeptic drugs. They authorize also the differentiation in the sub-group of "antipsychotics" of substances with a dominant neuroplegic or neuroleptic activity and others, such as lithium, which do not have this activity. This revision of the terminology avoids the confusion maintained by the use of terms "tranquillisers" and "neuroleptics" in the classification of psychotropic drugs.

  2. Positive predictive value of a case definition for diabetes mellitus using automated administrative health data in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid study

    Science.gov (United States)

    2012-01-01

    Background We developed and validated an automated database case definition for diabetes in children and youth to facilitate pharmacoepidemiologic investigations of medications and the risk of diabetes. Methods The present study was part of an in-progress retrospective cohort study of antipsychotics and diabetes in Tennessee Medicaid enrollees aged 6–24 years. Diabetes was identified from diabetes-related medical care encounters: hospitalizations, outpatient visits, and filled prescriptions. The definition required either a primary inpatient diagnosis or at least two other encounters of different types, most commonly an outpatient diagnosis with a prescription. Type 1 diabetes was defined by insulin prescriptions with at most one oral hypoglycemic prescription; other cases were considered type 2 diabetes. The definition was validated for cohort members in the 15 county region geographically proximate to the investigators. Medical records were reviewed and adjudicated for cases that met the automated database definition as well as for a sample of persons with other diabetes-related medical care encounters. Results The study included 64 cases that met the automated database definition. Records were adjudicated for 46 (71.9%), of which 41 (89.1%) met clinical criteria for newly diagnosed diabetes. The positive predictive value for type 1 diabetes was 80.0%. For type 2 and unspecified diabetes combined, the positive predictive value was 83.9%. The estimated sensitivity of the definition, based on adjudication for a sample of 30 cases not meeting the automated database definition, was 64.8%. Conclusion These results suggest that the automated database case definition for diabetes may be useful for pharmacoepidemiologic studies of medications and diabetes. PMID:22920280

  3. Positive predictive value of a case definition for diabetes mellitus using automated administrative health data in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid study

    Directory of Open Access Journals (Sweden)

    Bobo William V

    2012-08-01

    Full Text Available Abstract Background We developed and validated an automated database case definition for diabetes in children and youth to facilitate pharmacoepidemiologic investigations of medications and the risk of diabetes. Methods The present study was part of an in-progress retrospective cohort study of antipsychotics and diabetes in Tennessee Medicaid enrollees aged 6–24 years. Diabetes was identified from diabetes-related medical care encounters: hospitalizations, outpatient visits, and filled prescriptions. The definition required either a primary inpatient diagnosis or at least two other encounters of different types, most commonly an outpatient diagnosis with a prescription. Type 1 diabetes was defined by insulin prescriptions with at most one oral hypoglycemic prescription; other cases were considered type 2 diabetes. The definition was validated for cohort members in the 15 county region geographically proximate to the investigators. Medical records were reviewed and adjudicated for cases that met the automated database definition as well as for a sample of persons with other diabetes-related medical care encounters. Results The study included 64 cases that met the automated database definition. Records were adjudicated for 46 (71.9%, of which 41 (89.1% met clinical criteria for newly diagnosed diabetes. The positive predictive value for type 1 diabetes was 80.0%. For type 2 and unspecified diabetes combined, the positive predictive value was 83.9%. The estimated sensitivity of the definition, based on adjudication for a sample of 30 cases not meeting the automated database definition, was 64.8%. Conclusion These results suggest that the automated database case definition for diabetes may be useful for pharmacoepidemiologic studies of medications and diabetes.

  4. Positive predictive value of a case definition for diabetes mellitus using automated administrative health data in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid study.

    Science.gov (United States)

    Bobo, William V; Cooper, William O; Stein, C Michael; Olfson, Mark; Mounsey, Jackie; Daugherty, James; Ray, Wayne A

    2012-08-24

    We developed and validated an automated database case definition for diabetes in children and youth to facilitate pharmacoepidemiologic investigations of medications and the risk of diabetes. The present study was part of an in-progress retrospective cohort study of antipsychotics and diabetes in Tennessee Medicaid enrollees aged 6-24 years. Diabetes was identified from diabetes-related medical care encounters: hospitalizations, outpatient visits, and filled prescriptions. The definition required either a primary inpatient diagnosis or at least two other encounters of different types, most commonly an outpatient diagnosis with a prescription. Type 1 diabetes was defined by insulin prescriptions with at most one oral hypoglycemic prescription; other cases were considered type 2 diabetes. The definition was validated for cohort members in the 15 county region geographically proximate to the investigators. Medical records were reviewed and adjudicated for cases that met the automated database definition as well as for a sample of persons with other diabetes-related medical care encounters. The study included 64 cases that met the automated database definition. Records were adjudicated for 46 (71.9%), of which 41 (89.1%) met clinical criteria for newly diagnosed diabetes. The positive predictive value for type 1 diabetes was 80.0%. For type 2 and unspecified diabetes combined, the positive predictive value was 83.9%. The estimated sensitivity of the definition, based on adjudication for a sample of 30 cases not meeting the automated database definition, was 64.8%. These results suggest that the automated database case definition for diabetes may be useful for pharmacoepidemiologic studies of medications and diabetes.

  5. Efficacy of Adenine in the Treatment of Leukopenia and Neutropenia Associated with an Overdose of Antipsychotics or Discontinuation of Lithium Carbonate Administration: Three Case Studies.

    Science.gov (United States)

    Tomita, Takashi; Goto, Hidekazu; Sumiya, Kenji; Yoshida, Tadashi; Tanaka, Katsuya; Kohda, Yukinao

    2016-11-30

    Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose.

  6. Atypical odontalgia--an update.

    Science.gov (United States)

    Patel, Seena B; Boros, Audrey L; Kumar, Satish K S

    2012-09-01

    Atypical odontalgia is a commonly misdiagnosed condition that frequently leads to unnecessary dental treatments such as extraction and endodontic therapy. These treatments often worsen the pain. Despite greater recognition and understanding of this condition, proper diagnosis and