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Sample records for antipsychotic agents

  1. A computational network analysis based on targets of antipsychotic agents.

    Science.gov (United States)

    Gao, Lei; Feng, Shuo; Liu, Zhao-Yuan; Wang, Jiu-Qiang; Qi, Ke-Ke; Wang, Kai

    2018-03-01

    Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum. By protein-protein interaction (PPI) network analysis, a PPI network with 77 significantly interconnected target genes was generated. By historeceptomics analysis, significant brain region specific target-drug interactions were identified in targets of dopamine receptors (DRD1-Olanzapine in caudate nucleus and pons (P-valueantipsychotic targets and insights for molecular mechanism of antipsychotic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Discovery of potential antipsychotic agents possessing pro-cognitive properties.

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    Lameh, Jelveh; McFarland, Krista; Ohlsson, Jorgen; Ek, Fredrik; Piu, Fabrice; Burstein, Ethan S; Tabatabaei, Ali; Olsson, Roger; Bradley, Stefania Risso; Bonhaus, Douglas W

    2012-03-01

    Current antipsychotic drug therapies for schizophrenia have limited efficacy and are notably ineffective at addressing the cognitive deficits associated with this disorder. The present study was designed to develop effective antipsychotic agents that would also ameliorate the cognitive deficits associated with this disease. In vitro studies comprised of binding and functional assays were utilized to identify compounds with the receptor profile that could provide both antipsychotic and pro-cognitive features. Antipsychotic and cognitive models assessing in vivo activity of these compounds included locomotor activity assays and novel object recognition assays. We developed a series of potential antipsychotic agents with a novel receptor activity profile comprised of muscarinic M(1) receptor agonism in addition to dopamine D(2) antagonism and serotonin 5-HT(2A) inverse agonism. Like other antipsychotic agents, these compounds reverse both amphetamine and dizocilpine-induced hyperactivity in animals. In addition, unlike other antipsychotic drugs, these compounds demonstrate pro-cognitive actions in the novel object recognition assay. The dual attributes of antipsychotic and pro-cognitive actions distinguish these compounds from other antipsychotic drugs and suggest that these compounds are prototype molecules in the development of novel pro-cognitive antipsychotic agents.

  3. Risk of venous thromboembolism during treatment with antipsychotic agents.

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    Masopust, Jiří; Malý, Radovan; Vališ, Martin

    2012-12-01

    The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first-generation low-potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second-generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

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

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    Hermes, Eric D A; Sernyak, Michael; Rosenheck, Robert

    2013-04-01

    Anecdotal evidence suggests that second-generation antipsychotic agents are increasingly used to treat sleep problems. This study sought to quantify the proportion of new prescriptions for second-generation antipsychotic agents started for sleep/sedation and the correlates of such use. A cross-sectional survey of provider decision making at the time second-generation antipsychotic agents were prescribed, documenting the reasons for the medication, patient demographics, psychiatric and medical diagnoses, patient health characteristics, and provider background. A single Veterans Affairs Medical Center over a 20-month period. Prescribers of second-generation antipsychotic agents. N/A. Seven hundred seven (32.2%) of 2,613 surveys indicated sleep/sedation was at least one reason for using a second-generation anti-psychotic agent, whereas for 266 (12.1%) it was the only reason. Quetiapine was most frequently prescribed overall as well as for sleep/sedation (47.0% and 73.6% respectively). Second-generation antipsychotic agent use for sleep/sedation was unrelated to sociodemographic characteristics, least likely in patients with schizophrenia or bipolar disorder, and most likely as a newly started second-generation antipsychotic agent. Sleep/sedation is a common reason given for new prescriptions of second-generation antipsychotic agents. Quetiapine is most frequently used for this purpose. A greater understanding of why providers use second-generation antipsychotic agents rather than safer and less costly alternatives for sleep problems may advance the development of interventions to reduce adverse effects.

  5. Quinoline- and isoquinoline-sulfonamide analogs of aripiprazole: novel antipsychotic agents?

    Science.gov (United States)

    Zajdel, Pawel; Partyka, Anna; Marciniec, Krzysztof; Bojarski, Andrzej J; Pawlowski, Maciej; Wesolowska, Anna

    2014-01-01

    The introduction of typical antipsychotics over six decades ago signaled an important milestone in psychiatry. However, second-generation antipsychotics ameliorated the positive symptoms of schizophrenia but displayed limited effectiveness for the negative and cognitive symptoms. In addition, while the newer antipsychotics produced fewer motor side effects, the atypical antipsychotics still induced weight gain and endocrinopathies. In recent years, a third generation of antipsychotics was identified. Aripiprazole was the first approved drug acting as a D2 partial agonist/functionally selective ligand. This review presents the state of the development of novel antipsychotic dopaminergic and non-dopaminergic agents, supported by an overview of the compounds evaluated under advanced preclinical and clinical development (e.g., cariprazine and brexpiprazole). In line with the recent trends in the development of modern atypical antipsychotics, we present our strategic development of long-chain arylpiperazine-derived quinoline- and isoquinoline-sulfonamide displaying a multireceptor binding profile and partial D2 receptor agonism.

  6. Risk of serious cardiac events in older adults using antipsychotic agents.

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    Mehta, Sandhya; Chen, Hua; Johnson, Michael; Aparasu, Rajender R

    2011-04-01

    Antipsychotic agents can lead to severe cardiovascular adverse events due to multiple mechanisms involving electrophysiologic and metabolic effects. Few epidemiologic studies have evaluated the risk of serious cardiovascular-related events in typical and atypical antipsychotic users. The purpose of this study was to compare the risk of serious cardiac events in older adults taking typical antipsychotics with those taking atypical antipsychotics. Prescription and medical information were derived from the IMS LifeLink Health Plan Claims database. The study involved a retrospective cohort of older adults (≥50 years) taking atypical or typical antipsychotics from July 1, 2000, to December 31, 2007. The primary outcome measure was hospitalization or emergency room visit due to serious cardiac events, including thromboembolism, myocardial infarction, cardiac arrest, and ventricular arrhythmias within 1 year after the index date. The 2 groups were matched on a propensity score to minimize the baseline differences between the groups. Survival analysis was conducted on the matched cohort to assess the risk of serious cardiovascular events in typical versus atypical users. A total of 5580 patients were selected in each antipsychotic users group after propensity score matching. Serious cardiac events were found in 666 (11.9 %) atypical antipsychotic users and 698 (12.4%) typical antipsychotic users. Survival analysis revealed that typical antipsychotic users were at increased risk of serious cardiovascular events compared with atypical antipsychotic users (hazard ratio = 1.21; 95% CI, 1.04-1.40) after controlling for other factors. Moderate increases in risk of serious cardiac events are associated with older adults using typical antipsychotic agents compared with atypical users. Health care professionals should carefully evaluate the benefit/risk ratio of antipsychotic agents before prescribing these agents to a vulnerable population. Copyright © 2011 Elsevier HS Journals

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  8. The association between antipsychotic agents and the risk of myocardial infarction: a systematic review.

    Science.gov (United States)

    Brauer, Ruth; Douglas, Ian; Smeeth, Liam

    2011-12-01

    Patient populations that are prescribed antipsychotic agents have higher cardiovascular mortality rates. The risk of myocardial infarction is influenced by various factors that are more prevalent in patients with a mental illness. The aim of this review was to determine whether the use of antipsychotic agents is associated with the incidence of myocardial infarction in adults. Using multiple sources, all studies of antipsychotic agents using myocardial infarction as primary or secondary outcome measures were considered for inclusion. Study populations were adult subjects who had been prescribed an antipsychotic agent at least once in their medical history. It total, five studies were identified. Four studies with small numbers of events reported a moderate to strong effect of typical antipsychotic agents on the risk of myocardial infarction. The largest study had a favourable internal validity compared with all other studies and reported no association between the risk of myocardial infarction and current use of either atypical (relative risk 0.98, 95% confidence interval [CI] 0.88, 1.09) or typical antipsychotic agents (relative risk 0.99, 95% CI 0.96, 1.03). Clinical and methodological heterogeneity between the studies in this review led to an inconclusive answer to the question whether the use of antipsychotics is associated with the incidence of myocardial infarction in adults. Whilst results conflicted, the largest study did not find an association between the use of antipsychotic agents and an increased risk of myocardial infarction. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  9. Tardive dyskinesia from atypical antipsychotic agents in patients with mood disorders in a clinical setting.

    Science.gov (United States)

    Coplan, Jeremy; Gugger, James J; Tasleem, Hina

    2013-09-25

    There is a paucity of information on the risks and clinical characteristics of tardive dyskinesia with atypical antipsychotic agents in patients with mood and anxiety disorders in clinical practice. The authors retrospectively screened the charts of 268 patients with a mood or anxiety disorder treated with atypical antipsychotic agents from a psychiatric practice. Fifteen patients who developed tardive dyskinesia were identified and further data was collected on these patients. Tardive dyskinesia occurred in 5.9% of patients after exposure to an atypical antipsychotic agent for a mean of 28.7 months (range: 1-83). The average dosage of the offending agent in chlorpromazine equivalents was 350 mg/day (range: 67-969). All patients experienced oral-buccal-lingual stereotypy, which was frequently severe in nature, but completely resolved in all but one patient. Most patients (90.9%) who consented to a second trial of an atypical antipsychotic did not experience a relapse of TD. All patients were treated in a clinical practice setting by a single psychiatrist, which may limit the generalizability of the findings. The observed rate of TD represents a real world estimate of the risk of TD with atypical antipsychotic agents in patients with mood disorders. Fortunately, with early recognition symptoms appear to be reversible and further treatment with another atypical antipsychotic does not necessarily lead to relapse. © 2013 Elsevier B.V. All rights reserved.

  10. Incident users of antipsychotic agents and future use of cholesterol-lowering drugs: an observational, pharmacoepidemiologic study.

    Science.gov (United States)

    Skrede, Silje; Tvete, Ingunn F; Tanum, Lars; Steen, Vidar M; Bramness, Jørgen G

    2015-01-01

    Antipsychotic agents have serious metabolic adverse effects, among them dyslipidemia, which may necessitate secondary prophylaxis with cholesterol-lowering drugs. Second-generation antipsychotics (SGAs), particularly clozapine and olanzapine, are known to confer a higher risk of metabolic adverse effects than first-generation antipsychotics (FGAs). However, little is known regarding the real-life number of antipsychotic-treated patients receiving statins. By extracting data from the Norwegian prescription database, all patients 18-69 years old that started treatment with an antipsychotic during 2004-2012 formed the basis for analysis (n = 301,713). The primary outcome measure was the proportion of FGA and SGA users prescribed with cholesterol-lowering agent during the same period. We used Cox proportional hazards regression to evaluate the risk of redeeming a cholesterol-lowering drug for formerly antipsychotic drug-naive patients (n = 147,218). Statin prescription rates in patients receiving antipsychotic agents were lower (5.3%) than comparable rates in studies covering the general population (34%) and lower than would be expected based on the recognized negative impact of antipsychotics on serum lipids. Statin prescription rates were affected by patient age, antipsychotic dose, and the number of antipsychotic agents prescribed, but rates were only 5% elevated in patients receiving SGAs compared to patients receiving FGAs (P = .048). Our results may support the notion that patients treated with antipsychotic agents receive suboptimal care with regard to metabolic adverse effects. © Copyright 2015 Physicians Postgraduate Press, Inc.

  11. Risk of death in dual-eligible nursing home residents using typical or atypical antipsychotic agents.

    Science.gov (United States)

    Aparasu, Rajender R; Chatterjee, Satabdi; Mehta, Sandhya; Chen, Hua

    2012-11-01

    Antipsychotic use among dual-eligible nursing home residents is a concern for cost and safety considerations. To examine the comparative risk of death in dual-eligible elderly nursing home residents using typical and atypical agents. A retrospective cohort design matched on propensity score was used to examine the risk of death due to antipsychotic use among dual-eligible nursing home residents 65 years or older from four states. New typical and atypical users in nursing homes were followed for 6 months after the exposure without any censoring. The risk of death was modeled using the Cox proportional model and the extended Cox hazard model stratified on matched pairs based on propensity score. The unadjusted mortality rate was 18.42% for atypical antipsychotic users and 24.06% for typical antipsychotic users. The Cox proportional-hazards regression model revealed significant increased risk of death [hazard ratio (HR), 1.41; 95% confidence interval (CI), 1.27-1.57] among typical users when compared with atypical users. The extended Cox model, used due to the violation of proportional hazards assumption, revealed that risk of death was nearly twice as great among typical antipsychotic users within 40 days of antipsychotic treatment (HR, 1.81; 95% CI, 1.49-2.18) when compared with atypical users. However, moderate increase in risk (HR, 1.24; 95% CI, 1.09-1.42] was observed for 40-180 days of typical antipsychotic exposure. The use of typical antipsychotic agents was associated with highest risk of all-cause mortality within 40 days of typical antipsychotic use when compared with atypical use, and the risk decreased after 40 days among dual-eligible elderly nursing home residents.

  12. Second-generation long-acting injectable antipsychotic agents: an overview.

    Science.gov (United States)

    2012-09-01

    For over 40 years, antipsychotic drugs have been used as long-term maintenance treatment to control symptoms and reduce relapse rates in patients with schizophrenia. 'First-generation' oral agents such as haloperidol and chlorpromazine are associated with high levels of unwanted neurological effects and poor rates of patient adherence.1,2 Long-acting ('depot') injections of antipsychotics were developed to try to improve adherence. 'Second-generation' antipsychotic agents (also known as atypical antipsychotics) were introduced into clinical practice over 16 years ago. Although these agents have a lower propensity to cause extrapyramidal side effects, they are associated with a range of other unwanted effects (e.g. weight gain and its sequelae).1,3,4 Initially, second-generation agents were only available as orally administered medicines. Three long-acting injectable formulations of second-generation antipsychotics are now available in the UK: olanzapine embonate injection (ZypAdhera), paliperidone injection (Xeplion) and risperidone injection (Risperdal Consta). In this article we review the evidence for these agents and discuss the practical implications of their use.

  13. Antipsychotic agents in the treatment of anorexia nervosa: neuropsychopharmacologic rationale and evidence from controlled trials.

    Science.gov (United States)

    Brewerton, Timothy D

    2012-08-01

    The search for an effective psychopharmacologic strategy in the treatment of anorexia nervosa (AN) has been elusive for decades and has run the gamut from reserpine to typical antipsychotics, to lithium, to tetrahydrocannabinol, to growth hormone, to anticonvulsants, to antidepressants, to atypical antipsychotics. Only recently has there arisen a potential "diamond in the rough" in the form of the atypical antipsychotic agent, olanzapine, which, in four randomized clinical trials, has shown superiority to placebo (two studies), chlorpromazine (one study), and aripiprazole (one study) in terms of weight gain and/or reduction in obsessional symptoms. The pharmacologic profile of olanzapine and other antipsychotic medications is discussed in light of the known pathophysiology of AN involving serotonin and dopamine systems, as well as brain-derived neurotrophic factor.

  14. Measurement of treatment adherence with antipsychotic agents in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Xinhua S Ren

    2009-09-01

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

  15. 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

  16. Risk of falls and fractures in older adults using antipsychotic agents: a propensity-matched retrospective cohort study.

    Science.gov (United States)

    Mehta, Sandhya; Chen, Hua; Johnson, Michael L; Aparasu, Rajender R

    2010-10-01

    Antipsychotics, especially atypical agents, are widely used in the elderly population to treat behavioural and psychiatric symptoms. Very few studies have compared the risk of falls and fractures among older adults using typical and atypical agents and none of the studies have evaluated differential risk across antipsychotic classes. To examine the risk of falls and fractures associated with atypical antipsychotic use and typical antipsychotic use in community-dwelling older adults in the US. The study involved a retrospective population-based cohort design matched on propensity scores involving older adults (aged ≥50 years) using atypical or typical antipsychotic agents in the IMS LifeLink™ Health Plan Claims Database. Patients taking atypical antipsychotics were matched with patients taking typical antipsychotics using the Greedy 5 → 1 matching technique. The study evaluated the relative risk of hospitalization/emergency room (ER) visits due to falls/fractures in a 1-year follow-up period, and patients treated with atypical antipsychotics were compared with those treated with typical antipsychotics using the Cox proportional-hazards regression model stratified on matched pairs. The covariates adjusted for in the regression model included duration of therapy and exposure to other psychotropic medications that increase the risk of falls and fractures. From July 2000 to December 2007, 11 160 (5580 atypical and 5580 typical) users of antipsychotics were obtained after matching on propensity scores. A total of 825 cases of falls/fractures with at least one hospitalization/ER visit following the use of antipsychotic agents were identified. The number of cases with falls/fractures was 450 in atypical antipsychotic users and 375 in typical antipsychotic users. Cox regression model analysis revealed no statistically significant difference between atypical users and typical users with respect to risk of falls/fractures (hazard ratio [HR] 1.01; 95% CI 0.83, 1

  17. Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents.

    Science.gov (United States)

    Gjerden, Pål; Slørdal, Lars; Bramness, Jørgen G

    2009-12-01

    The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

  18. The lipid profiles in Japanese patients with schizophrenia treated with antipsychotic agents.

    Science.gov (United States)

    Watanabe, Junzo; Suzuki, Yutaro; Sugai, Takuro; Fukui, Naoki; Ono, Shin; Tsuneyama, Nobuto; Saito, Mami; Someya, Toshiyuki

    2012-01-01

    Antipsychotic-treated schizophrenia patients are susceptible to dyslipidemia. However, the results of previous studies of North American and UK populations including various races have been contradictory with regard to which lipid measure was the most affected in patients with schizophrenia taking antipsychotic agents. The aim of this study was to investigate the effect of schizophrenia patients receiving antipsychotic agents on each lipid measure in a Japanese population. The samples included 136 control individuals and 157 patients with schizophrenia treated with antipsychotic agents. Age, gender distribution and body mass index (BMI) of the controls were matched with the patients. The high-density lipoprotein cholesterol (HDL-cholesterol) levels were significantly lower in patients than in the control subjects (Pantipsychotics was an independent predictor of decreased HDL-cholesterol. An increased BMI, male gender and cigarette smoking were also major predictors of a decreased HDL-cholesterol level (r(2)=0.42, Pantipsychotic agents, the HDL-cholesterol levels should be closely monitored in all patients, even those who are not obese or do not smoke, to decrease their risk of cardiovascular disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Off-label use of second-generation antipsychotic agents among elderly nursing home residents.

    Science.gov (United States)

    Kamble, Pravin; Sherer, Jeff; Chen, Hua; Aparasu, Rajender

    2010-02-01

    This study examined off-label and evidence-based use of second-generation antipsychotic agents among elderly nursing home residents and factors associated with off-label use. This study involved a retrospective, cross-sectional analysis of data from the 2004 National Nursing Home Survey (NNHS). The sample included nursing home residents 65 years and older who received second-generation antipsychotic agents. This study used an indication-based definition of off-label use established by the U.S. Food and Drug Administration (FDA). Evidence-based use included FDA-approved indications and indications for which the Agency of Healthcare Research and Quality found at least moderate strength of evidence of effectiveness. Descriptive statistics were used to examine the prevalence of off-label and evidence-based use. Multiple logistic regression was used to examine the patient and facility factors associated with off-label use of second-generation antipsychotics. According to the 2004 NNHS, 308,990 (23.5%) elderly nursing home residents received at least one second-generation antipsychotic agent. Of those using second-generation antipsychotics, 86.3% received them for off-label indications and 56.9% received them for an evidence-based use. Multivariate analysis found that age (> or =75 years), self-pay for nursing home care, diagnosis of dementia, and residing in a nonprofit nursing home were positively associated with off-label use, whereas receiving Medicaid benefits was negatively associated with such use. Although second-generation antipsychotics were frequently used for off-label indications, most of the usage was evidence based among elderly nursing home residents. However, the high level of non-evidence-based use combined with recent safety and efficacy data suggests an urgent need to address the evidence base for this vulnerable population.

  20. Antipsychotic agents used to augment clozapine during long-term inpatient hospitalizations.

    Science.gov (United States)

    Leung, J G; Chengappa, K N R; Ivanov, E; Gandotra, G; Kahn, C E; Weber, J S; Fabian, T J

    2014-11-01

    Literature assessing effective clozapine augmentation strategies is limited. The aim of this retrospective evaluation was to examine antipsychotics used to augment clozapine and assess whether an augmentation antipsychotic would continue at discharge. Demographic, clinical and pharmacy data were collected retrospectively if patients had received clozapine plus an antipsychotic used for augmentation. The dose of the augmentation agent, length of augmentation therapy, and concomitant medications were collected. Of the 49 patients (mean age 45.3±12.1 years), 27 (55%) were male. The mean clozapine dose at discharge was 406.1±121.8 mg. When a first generation antipsychotic (FGA) was selected initially to augment clozapine there was a greater likelihood it would be continued until discharge compared to a second generation antipsychotic (SGA) (78 vs. 50%, OR=3.6, 95% CI 1.03-12.6). FGAs (3.2%) compared to SGAs (35%) were less likely to be discontinued due to a documented lack of benefit when first selected to augment clozapine (OR=16.2, 95% CI 2-131.3). Electroconvulsive therapy plus clozapine was found to be beneficial in several patients (n=14) who failed at least 1 augmentation strategy. This real world data suggests that adding an antipsychotic to clozapine is a reasonable approach to those who do not fully respond to clozapine monotherapy. While comparisons of all agents could not be conducted from this small retrospective study, these data suggest FGAs should be investigated in future studies as potential agents to successfully augment clozapine therapy. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Recent developments in the discovery of novel antipsychotic agents modualating dopamine and serotonin receptors.

    Science.gov (United States)

    Li, Xin; Ma, Shutao

    2013-07-01

    Currently, schizophrenia, as a serious psychiatric disorder, continues affecting the quality of life in the psychotics. This disease is often debilitating and chronic, showing broad symptoms at one end by hallucinations, delusions, thought disorder and the other end by affective flattening, catatonia, social isolation. In order to combat this disease, many antipsychotic drugs have been developed and introduced into clinical practice in the past half century. However, only a small minority of them can treat effectively schizophrenia without side effects. In view of this situation, high attention has been given to the exploration of desired antipsychotic agents influential especially through the modulation of dopamine and serotonin receptors with substantial strides made in recent years, leading to the discovery of many novel chemical entities with intriguing profiles. In this review, we summarize novel structural antipsychotics in development and discuss the future direction of ideal antipsychotic drug candiates. In particular, the promising atypical antipsychotic profiles of new molecules and the inspirations for their design are highlighted.

  2. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    David O'Sullivan

    Full Text Available 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 (MS4, 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.

  3. Risk of cerebrovascular adverse events in older adults using antipsychotic agents: a propensity-matched retrospective cohort study.

    Science.gov (United States)

    Mehta, Sandhya; Johnson, Michael L; Chen, Hua; Aparasu, Rajender R

    2010-06-01

    To compare the risk of cerebrovascular adverse events with second-generation antipsychotic users versus those taking first-generation antipsychotics in community-dwelling older adults. A population-based retrospective cohort study matched on propensity score was used to examine the risk of cerebrovascular adverse events in second-generation antipsychotic users compared to first-generation antipsychotic users. IMS LifeLink Health Plan Claims Database was used to identify older adults (> or = 50 years) taking second-generation or first-generation antipsychotic agents from July 1, 2000, to December 31, 2007. Cox proportional hazards regression model stratified on matched pairs was used to examine the risk of hospitalization or emergency visits due to cerebrovascular adverse events within 1 year of follow-up (primary outcome measure). The covariates adjusted for include duration of therapy and exposure to other medication increasing risk of cerebrovascular adverse events. A total of 11,160 older adults (5,580 second-generation and 5,580 first-generation antipsychotic users) matched on propensity score was obtained. Regression analysis revealed that no statistically significant difference exists between second-generation and first-generation antipsychotic users with respect to risk of cerebrovascular adverse events (hazard ratio [HR], 0.858; 95% CI, 0.689-1.446). However, duration of therapy between 30-90 days (HR, 1.707; 95% CI, 1.174-2.481) and more than 90 days (HR, 1.570; 95% CI, 1.132-2.176) was associated with increased risk of cerebrovascular adverse events compared to duration of therapy less than 30 days. The use of second-generation antipsychotic agents was found not to be associated with increased risk of cerebrovascular adverse events compared to first-generation agents in older adults. However, long-term use of second- and first-generation antipsychotic agents is associated with increased risk of cerebrovascular adverse events. 2010 Physicians Postgraduate

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

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2014-03-01

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

  5. Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents.

    Science.gov (United States)

    Peprah, Kwakye; Zhu, Xue Y; Eyunni, Suresh V K; Setola, Vincent; Roth, Bryan L; Ablordeppey, Seth Y

    2012-02-01

    Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology. Published by Elsevier Ltd.

  6. Pharmacoeconomic comparison of ziprasidone with other atypical oral antipsychotic agents in schizophrenia

    Directory of Open Access Journals (Sweden)

    Andrea Fagiolini

    2011-03-01

    Full Text Available Objective: to comparatively investigate – by means of computer simulations – the economic cost and clinical outcomes of five atypical oral antipsychotic agents (ziprasidone, olanzapina, risperidone, paliperidone and aripiprazolo.Methods: a cyclical stochastic model representing patient evolution, taking into account main adverse reactions (akathisia, weight gain and extra-pyramidal ARs, drug efficacy on psychosis stabilization and probability of relapse, was developed. Ten different scenarios were compared, each starting with one of the considered antipsychotics, prescribed either at home or in a hospital setting. Switching to another medication was allowed until no untried drugs were available, in which case clozapine treatment or admission to a Psychiatric Therapeutic Rehabilitation Center were irreversibly assigned. Model inputs were probabilities of ARs, probabilities of stabilization and probabilities of destabilization (assumed equal for all; as well as costs attributable to drugs, hospitalization, outpatient care and costs adverse reactions in terms of concomitant medications. Sources for the inputs were the trials reported in the most recent literature (from the year 2000, selected based on the homogeneity of the observational period and antipsychotic dosage used.Results: in each scenario, the hospitalization cost represented the highest component of the overall cost (approximately 67%. Assuming equal drug effectiveness, ziprasidone fared better than all other considered competitors, showing the lowest average annual costs per patient (and also the lowest average annual hospitalization costs as well as the largest numbers of controlled months without adverse reactions, independently of the initial setting. Conclusions: the most important determinant of total cost appears to be hospitalization, whose cost is about 600% higher than the medications cost. Medication effectiveness and tolerability remain however of utmost importance for

  7. 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.

  8. Cardiovascular risk factors in chronic treatment with antipsychotic agents used in primary care.

    Science.gov (United States)

    Mundet-Tudurí, Xavier; Iglesias-Rodal, Manuel; Olmos-Domínguez, Carmen; Bernard-Antoranz, M Lluïsa; Fernández-San Martín, M Isabel; Amado-Guirado, Ester

    2013-12-01

    To compare the prevalence of cardiovascular risk factors (CVRF) and vascular events, between patients treated and untreated with antipsychotic drugs. A cross-sectional study was done in Barcelona. We compared patients attended in Primary Health Care Centres, treated with or without antipsychotics between 2008 and 2010. Anthropometric measurements, clinical variables, and CVRF were assessed. Adult and elderly patients, typical and atypical antipsychotics, were studied separately. 14,087 patients had been prescribed antipsychotics (63.4% atypical), the most common being risperidone. We selected 13,724 patients with the same age and gender but not treated (total of 27,811 patients). Patients receiving antipsychotic had higher prevalence of obesity (16.9% vs. 11.9%), smoking (22.2% vs. 11.1%), diabetes mellitus (16% vs. 11.9%), and dyslipidemia (32.8% vs. 25.8%) (p antipsychotic, differences were not observed depending typical or atypical ones. Patients treated with antipsychotic drugs had a greater prevalence of several CVRF (diabetes mellitus, obesity, and smoking). The presence of stroke was higher in those treated with antipsychotics. No relevant differences were observed between patients receiving typical or atypical antipsychotics.

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

    Directory of Open Access Journals (Sweden)

    Irina Vasilyeva

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

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

    Science.gov (United States)

    Vasilyeva, Irina; Biscontri, Robert G; Enns, Murray W; Metge, Colleen J; Alessi-Severini, Silvia

    2013-01-01

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

  11. Late potentials in the signal-averaged electrocardiogram in schizophrenia patients maintained on antipsychotic agents: a preliminary naturalistic study.

    Science.gov (United States)

    Nahshoni, Eitan; Strasberg, Boris; Imbar, Shula; Rotem, Ofer; Gur, Shay; Hermesh, Hagai; Weizman, Abaraham

    2010-03-01

    In the present, preliminary, naturalistic study, cardiac ventricular late potentials (LPs), were measured in 33 physically healthy schizophrenia patients (13 - females and 26 - males, age - 45.5+/-8.8years) maintained on typical and atypical antipsychotic agents. These LPs represent delayed ventricular activation that might predispose to fatal ventricular arrhythmias and sudden cardiac death (SCD) in cardiac patients. Sixteen of the 33 patients ( approximately 48%) were found to be positive for LPs (compared to 3.7-6% in the general population). No association was found with any of the following: drug type, anti-cholinergic burden, daily dose of antipsychotic agents, age, gender, disease duration, QT(c) interval and QT dispersion. Further large-scale longitudinal prospective studies are warranted to substantiate our findings and to clarify their impact on the excess cardiac morbidity and mortality in schizophrenia patients. Copyright 2009. Published by Elsevier B.V.

  12. Prevalence of the metabolic syndrome in schizophrenic patients receiving second-generation antipsychotic agents--a cross-sectional study.

    Science.gov (United States)

    Kagal, Urmila A; Torgal, Shashikant S; Patil, Nanasaheb M; Malleshappa, Anil

    2012-06-01

    The present study was taken up to assess the prevalence of the metabolic syndrome in schizophrenic patients receiving second-generation antipsychotic agents and to determine the most sensitive and specific clinical parameters used for screening of metabolic syndrome in these patients. The present study was taken up in a tertiary care hospital. Eighty patients diagnosed with schizophrenia and receiving a single second-generation antipsychotic for 3 months or more were enrolled in the study after obtaining written informed consent. Patients were screened for metabolic syndrome using American Heart Association and National, Heart, Lung and Blood Institute (AHA NHLBI)-modified National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP III) criteria. Prevalence of metabolic syndrome was found to be 35%. The clinical parameter with highest sensitivity for screening of metabolic syndrome is low-serum high-density lipoprotein cholesterol with a sensitivity of 89.28%. Elevated fasting blood glucose and increased waist circumference were found to have highest and equal specificity of 90.38%. There is a high prevalence of the metabolic syndrome in patients with schizophrenic patients receiving second-generation antipsychotic agents. Increasing awareness of this fact among psychiatrists will help to prevent, detect, and treat this condition that is associated with considerable morbidity and mortality.

  13. Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons.

    Science.gov (United States)

    Sahlberg, Marie; Holm, Ellen; Gislason, Gunnar H; Køber, Lars; Torp-Pedersen, Christian; Andersson, Charlotte

    2015-09-01

    Data from observational studies have raised concerns about the safety of treatment with antipsychotic agents (APs) in elderly patients with dementia, but this area has been insufficiently investigated. We performed a head-to-head comparison of the risk of major adverse cardiovascular events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. We followed all treatment-naïve Danish citizens aged ≥70 years that initiated treatment with APs for the first time between 1997 and 2011 (n=91 774, mean age 82±7 years, 35 474 [39%] were men). Incidence rate ratios associated with use of different APs were assessed by multivariable time-dependent Poisson regression models. For the first 30 days of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of levomepromazine (3.80, 95% CI 3.43 to 4.21) and haloperidol (1.85, 95% CI 1.67 to 2.05) and lower for treatment with flupentixol (0.54, 95% CI 0.45 to 0.66), ziprasidone (0.31, 95% CI 0.10 to 0.97), chlorprothixen (0.76, 95% CI 0.61 to 0.95), and quetiapine (0.68, 95% CI 0.58 to 0.80). Relationships were generally similar for long-term treatment. The majority of agents were associated with higher risks among patients with cardiovascular disease compared with patients without cardiovascular disease (P for interaction <0.0001). Similar results were observed for noncardiovascular mortality, although differences in associations between patients with and without cardiovascular disease were small. Our study suggested some diversity in risks associated with individual APs but no systematic difference between first- and second-generation APs. Randomized placebo-controlled studies are warranted to confirm our findings and to identify the safest agents. © 2015 The Authors. Published on behalf

  14. Risk of falls and fractures in older adults using atypical antipsychotic agents: a propensity score-adjusted, retrospective cohort study.

    Science.gov (United States)

    Chatterjee, Satabdi; Chen, Hua; Johnson, Michael L; Aparasu, Rajender R

    2012-04-01

    Atypical antipsychotic agents are extensively prescribed in the elderly to treat various behavioral and psychiatric disorders. Past literature has documented an increased risk of falls and factures with the use of risperidone and olanzapine compared with nonuse. However, none of the studies assessed the comparative safety profiles of atypical agents with respect to falls and fractures. The goal of this study was to evaluate the risk of falls and fractures associated with the use of risperidone, olanzapine, and quetiapine in community-dwelling adults aged ≥50 years. The study involved a propensity score-adjusted approach in new users of risperidone, olanzapine, or quetiapine anytime between July 1, 2000, and June 30, 2008, using data from the IMS LifeLink Health Plan Claims database. Patients were followed up until a hospitalization/emergency department visit for fall/fracture or the end of the study period, whichever occurred earlier. The Cox proportional hazards regression model was used to evaluate the comparative risk of falls/fractures. The covariates in the final model included propensity scores and their interaction terms. There were 12,145 new users of atypical agents in the study population (5083 risperidone, 4377 olanzapine, and 2685 quetiapine). A total of 417 cases of falls/fractures with at least 1 hospitalization/ emergency department visit after the use of the antipsychotic agents were identified. The number of falls for risperidone, olanzapine, and quetiapine were 179 (3.56%), 123 (2.84%), and 115 (4.34%), respectively. After adjusting for propensity scores, the Cox proportional hazards model showed that there was no statistically significant difference with use of risperidone (hazard ratio = 1.10 [95% CI, 0.86-1.39]) or quetiapine (hazard ratio = 1.12 [95% CI, 0.86-1.46]) compared with olanzapine (reference group) in the risk of falls or fractures. The study found no significant difference across the individual atypical agents in the risk of falls

  15. Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors.

    Science.gov (United States)

    Erzengin, Mahmut; Bilen, Cigdem; Ergun, Adem; Gencer, Nahit

    2014-02-01

    The antipsychotic drugs currently used to treat schizophrenia can be divided into two distinct classes, typical and atypical antipsychotics. Many drug molecules are enzyme inhibitors that bind reversibly or irreversibly to their target through intermolecular interactions. That's why enzyme inhibition studies are an important issue for drug design and biochemical applications. In this study, in vitro inhibition effect of some antipsychotic drugs on the purified carbonic anhydrase (CA) I and II isoenzymes were investigated by using CO2 as a substrate. CA I and II were purified from human erythrocytes by a simple one step procedure using Sepharose 4B-L-tyrosine-sulfonamide affinity column. The results showed that all the drugs inhibited the cytosolic carbonic anhydrases enzyme activity in a concentration-dependent fashion. Among the studied drugs, aripiprazole and pramipexole were found to be the most active one for hCA I (IC50: 3.64 and 5.37 μM) and hCA II (IC50: 4.16 and 4.81 μM) activity, respectively.

  16. Daytime sleepiness and EEG abnormalities in patients treated with second generation antipsychotic agents.

    Science.gov (United States)

    Okruszek, Lukasz; Jernajczyk, Wojciech; Wierzbicka, Aleksandra; Waliniowska, Elżbieta; Jakubczyk, Tomasz; Jarema, Marek; Wichniak, Adam

    2014-12-01

    The aim of this study was to verify whether or not an increased prevalence of excessive daytime sleepiness (EDS) or EEG abnormalities is observed in patients with schizophrenia spectrum disorders (SSD), and to compare the effects of second generation antipsychotics (SGA) on patients' daytime sleepiness level and EEG recordings. EEG recordings and self-reports of EDS, assessed with Epworth (ESS) and Stanford (SSS) Sleepiness Scales, were compared between 244 patients with SSD and 82 patients with anxiety, personality or behavioral disorders (non-psychotic disorders, NPD). To examine the effects of various SGA, patients treated in monotherapy with aripiprazole, olanzapine, clozapine, risperidone and sertindole were compared. A higher prevalence of abnormal EEG recordings was observed in SSD patients. No significant differences in average daytime sleepiness were found between patients with SSD and NPD; however, patients with SSD had longer sleep duration. Aripiprazole treatment was associated with significantly smaller and less frequent EEG abnormalities than treatment with any other SGA, while treatment with clozapine and olanzapine was related to an increased prevalence of severe EEG abnormalities. Patients with SSD treated with SGA in monotherapy were less sleepy than unmedicated patients with NPD. Although antipsychotics may have profound effects on EEG patients with schizophrenia do not have higher daytime sleepiness than patients with anxiety/personality disorders. Patients with schizophrenia may compensate sedative effects of antipsychotic treatment with sleep duration prolongation and report even less sleepiness than non-psychotic patients. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. Differential effects of antipsychotic agents on obsessive-compulsive symptoms in schizophrenia: a longitudinal study.

    Science.gov (United States)

    Schirmbeck, Frederike; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Esslinger, Christine; Meyer-Lindenberg, Andreas; Zink, Mathias

    2013-04-01

    Indirect evidence supports the assumption that antiserotonergic second-generation antipsychotics (SGA) induce and aggravate obsessive-compulsive symptoms (OCS) in schizophrenia. However, multimodal studies assessing the long-term interaction of pharmacotherapy and psychopathology are missing. Over 12 months, we followed-up 75 schizophrenia patients who were classified into two groups according to antipsychotic treatment: clozapine or olanzapine (group I) versus aripiprazole or amisulpride (group II). We applied the Yale Brown Obsessive Compulsive Scale (YBOCS) and investigated between-group changes over time as the primary endpoint. Group I showed markedly higher YBOCS scores at both time points. Repeated measure analyses of variance (ANOVAs) revealed significant interaction effects of group and time (per protocol sample (PP): p=0.006). This was due to persistently high OCS severity within group I, and decreasing YBOCS scores within group II. OCS severity correlated significantly with the negative and general psychopathology subscales of the Positive and Negative Syndrome Scale (PANSS), as well as with depressive symptoms. The progressive differences in OCS severity between our groups support the assumption of differential pharmacodynamic effects on comorbid OCS in schizophrenia. Further studies should address the pathogenetic mechanism, define patients at risk and facilitate early detection as well as therapeutic interventions.

  18. Dopamine D2S and D2L receptors may differentially contribute to the actions of antipsychotic and psychotic agents in mice.

    Science.gov (United States)

    Xu, R; Hranilovic, D; Fetsko, L A; Bucan, M; Wang, Y

    2002-01-01

    Regulation of dopamine D2 receptor (D2) function plays an important role in alleviating either the motor deficits of Parkinson's disease or psychotic symptoms of schizophrenia. D2 also plays a critical role in sensorimotor gating which can be measured by monitoring the prepulse inhibition of the startle response. Alternative splicing of the D2 gene generates two isoforms, D2S and D2L. Here we investigated the role of D2S and D2L in the mechanisms of action of dopaminergic drugs, using mice lacking D2L (D2L(-/-)) but expressing D2S as a model system. We found that the typical antipsychotic raclopride was much less potent in inhibiting locomotor activity and eliciting catalepsy (or parkinsonism) in D2L(-/-) mice, whereas the atypical antipsychotic clozapine was equally effective in D2L(-/-) and wild-type mice. These suggest that the deletion of D2L diminishes drug-induced parkinsonism. Furthermore, two dopamine agonists, amphetamine and apomorphine, reduced prepulse inhibition to a similar degree in D2L(-/-) and wild-type mice. These results together suggest that D2S alone can mediate the action of clozapine and the dopamine agonist-induced disruption of prepulse inhibition. The differential binding affinities of these agents for D2S vs D2L were not sufficient to explain the divergent effects of typical vs atypical antipsychotics in D2L(-/-) mice. These findings suggest that D2S and D2L may differentially contribute to the therapeutic actions and side effects of antipsychotic agents, and may have implications for developing better antipsychotic agents.

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

    Science.gov (United States)

    Nehme, Hassan; Saulnier, Patrick; Ramadan, Alyaa A; Cassisa, Viviane; Guillet, Catherine; Eveillard, Matthieu; Umerska, Anita

    2018-01-01

    Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs) on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC) assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio), the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.

  20. Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents.

    Science.gov (United States)

    Cheng, Jianjun; Giguère, Patrick M; Onajole, Oluseye K; Lv, Wei; Gaisin, Arsen; Gunosewoyo, Hendra; Schmerberg, Claire M; Pogorelov, Vladimir M; Rodriguiz, Ramona M; Vistoli, Giulio; Wetsel, William C; Roth, Bryan L; Kozikowski, Alan P

    2015-02-26

    The discovery of a new series of compounds that are potent, selective 5-HT2C receptor agonists is described herein as we continue our efforts to optimize the 2-phenylcyclopropylmethylamine scaffold. Modifications focused on the alkoxyl substituent present on the aromatic ring led to the identification of improved ligands with better potency at the 5-HT2C receptor and excellent selectivity against the 5-HT2A and 5-HT2B receptors. ADMET studies coupled with a behavioral test using the amphetamine-induced hyperactivity model identified four compounds possessing drug-like profiles and having antipsychotic properties. Compound (+)-16b, which displayed an EC50 of 4.2 nM at 5-HT2C, no activity at 5-HT2B, and an 89-fold selectivity against 5-HT2A, is one of the most potent and selective 5-HT2C agonists reported to date. The likely binding mode of this series of compounds to the 5-HT2C receptor was also investigated in a modeling study, using optimized models incorporating the structures of β2-adrenergic receptor and 5-HT2B receptor.

  1. Repurposing antipsychotic drugs into antifungal agents: Synergistic combinations of azoles and bromperidol derivatives in the treatment of various fungal infections.

    Science.gov (United States)

    Holbrook, Selina Y L; Garzan, Atefeh; Dennis, Emily K; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2017-10-20

    As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles. Exploring combination therapy that involves the current azoles and another drug has been shown to be a promising strategy. Haloperidol and its derivative, bromperidol, were originally discovered as antipsychotics. Herein, we synthesize and report a series of bromperidol derivatives and their synergistic antifungal interactions in combination with a variety of current azole antifungals against a wide panel of fungal pathogens. We further select two representative combinations and confirm the antifungal synergy by performing time-kill assays. Furthermore, we evaluate the ability of selected combinations to destroy fungal biofilm. Finally, we perform mammalian cytotoxicity assays with the representative combinations against three mammalian cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine.

    Science.gov (United States)

    Tsuda, Yoshiyuki; Saruwatari, Junji; Yasui-Furukori, Norio

    2014-03-04

    To clarify the effects of smoking on the disposition of two commonly used antipsychotics, olanzapine and clozapine, and to create standards to adjust the doses of these drugs in clinical practice based on the smoking status. A meta-analysis was conducted by searching MEDLINE, Scopus and the Cochrane Library for relevant prospective and retrospective studies. We included the studies that investigated the effects of smoking on the concentration to dose (C/D) ratio of olanzapine or clozapine. The weighted mean difference was calculated using a DerSimonian-Laird random effects model, along with 95% CI. Seven association studies, comprising 1094 patients (652 smokers and 442 non-smokers) with schizophrenia or other psychiatric disorders, were included in the meta-analysis of olanzapine. The C/D ratio was significantly lower in smokers than in non-smokers (p<0.00001), and the mean difference was -0.75 (ng/mL)/(mg/day) (95% CI -0.89 to -0.61). Therefore, it was estimated that if 10 and 20 mg/day of olanzapine would be administered to smokers, about 7 and 14 mg/day, respectively, should be administered to non-smokers in order to obtain the equivalent olanzapine concentration. Four association studies of clozapine were included in the meta-analysis of clozapine, comprising 196 patients (120 smokers and 76 non-smokers) with schizophrenia or other psychiatric disorders. The C/D ratio was significantly lower in smokers than in non-smokers (p<0.00001), and the mean difference was -1.11 (ng/mL)/(mg/day) (95% CI -1.53 to -0.70). Therefore, it was estimated that if 200 and 400 mg/day of clozapine would be administered to smokers, about 100 and 200 mg/day, respectively, should be administered to non-smokers. We suggest that the doses of olanzapine and clozapine should be reduced by 30% and 50%, respectively, in non-smokers compared with smokers in order to obtain an equivalent olanzapine or clozapine concentration.

  3. 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.

  4. The effects of six antipsychotic agents on QTc--an attempt to mimic clinical trial through simulation including variability in the population.

    Science.gov (United States)

    Glinka, Anna; Polak, Sebastian

    2014-04-01

    Many drugs (belonging to different chemical groups) have the potential for QT interval prolongation associated with ionic channel blockade in the cardiomyocyte membrane. Due to the fact that this phenomenon is linked to a higher risk of TdP, the ability to predict its scale is one of the most important outcomes of cardiotoxicity assessment of new agents. With use of the Cardiac Safety Simulator (CSS), the effect of six antipsychotic drugs was predicted in silico. Separate simulations were carried out for each studied population taking the drug. The aim of this study was to predict both the mean values of delta QTc and the results range. To be able to observe individual variability after drug administration, each patient was randomly assigned to the individual drug concentration. Also, appropriate diversity in heart rate, plasma electrolytes concentrations, morphometric parameters of ventricular myocytes, and one common hERG polymorphism frequency in population were added. Analyzing the results of simulation with Student's t-test, in five of six cases, there were no statistically significant differences between observed and predicted mean values. The diversity of results in all populations studied, however, was not fully reconstructed. The model was able to accurately reproduce the average effect of the drug on the length when the phenomenon is associated purely with blocking of ionic channels. Nevertheless, the problem of variability in the population and its effect on the QT interval requires further study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Novel versus conventional antipsychotic drugs.

    Science.gov (United States)

    Love, R C

    1996-01-01

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

  6. Evaluation of the Individual Safe Correction of Antipsychotic Agent Polypharmacy in Japanese Patients with Chronic Schizophrenia: Validation of Safe Corrections for Antipsychotic Polypharmacy and the High-Dose Method

    Science.gov (United States)

    Sukegawa, Tsuruhei; Inagaki, Ataru; Inada, Toshiya; Yoshio, Takashi; Yoshimura, Reiji; Iwata, Nakao

    2015-01-01

    Background: Polypharmacy for schizophrenia treatment is not justified by the available clinical evidence. We evaluated a treatment reduction approach that reduces the dose and number of antipsychotic medications simultaneously prescribed to patients. Methods: In a randomized open study of the Safe Correction of Antipsychotic Polypharmacy and High-Dose Prescriptions program funded by the Japanese Ministry of Health, Labour, and Welfare, we evaluated a drug reduction method consisting of a dose reduction intervention performed on 163 patients with schizophrenia for twelve or 24 weeks. One antipsychotic medication was removed each week from each patient’s treatment regimen by reducing the dose by 0 to 50 chlorpromazine equivalents. Data on health-related indices of quality of life, clinical symptoms, and risk of side effects were analyzed using a two-way repeated-measures mixed linear model. Results: Despite a 23% reduction in antipsychotic dose, no differences in outcomes were observed between the dose reduction and observation groups (effect size = 0.001 – 0.085, P = .24–.97), despite high statistical power (1-β = 0.48–0.97). The findings are limited by the nonuniformity of the participants’ treatment history, duration, and dose reduction amount. Dose reduction protocol patients exhibited no difference in psychotic symptoms or adverse events compared with the observation group. Conclusions: Importantly, the low dropout rate in our study (6.9% of participants withdrew because of patient factors and 23.8% for all secondary reasons) indicates that our “slowly” method is well tolerated. We hope that this approach will result in therapeutic improvements. PMID:25522380

  7. Intranasal delivery of antipsychotic drugs.

    Science.gov (United States)

    Katare, Yogesh K; Piazza, Justin E; Bhandari, Jayant; Daya, Ritesh P; Akilan, Kosalan; Simpson, Madeline J; Hoare, Todd; Mishra, Ram K

    2017-06-01

    Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

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

  9. A prospective flexible-dose study of paliperidone palmitate in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents.

    Science.gov (United States)

    Schreiner, Andreas; Bergmans, Paul; Cherubin, Pierre; Keim, Sofia; Rancans, Elmars; Bez, Yasin; Parellada, Eduard; Carpiniello, Bernardo; Vidailhet, Pierre; Hargarter, Ludger

    2014-10-01

    The goal of this study was to explore the tolerability, safety, and treatment response of flexible doses of once-monthly paliperidone palmitate (PP) in the subset of nonacute but symptomatic adult patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents in the PALMFlexS (Paliperidone Palmitate Flexible Dosing in Schizophrenia) study. This was an interventional, single-arm, international, multicenter, unblinded, 6-month study performed in patients with schizophrenia. Patients were categorized according to reasons for switching. In patients switching because of lack of efficacy or for other reasons, primary efficacy outcomes were the proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to last-observation-carried-forward end point) and maintained efficacy (defined as noninferiority in the change in PANSS total score at end point versus baseline [Schuirmann's test]), respectively. A total of 593 patients (intention-to-treat population) were enrolled: 63.1% were male; their mean (SD) age was 38.4 (11.8) years; and 78.6% had paranoid schizophrenia. The main reasons for transition to PP were patient's wish (n = 259 [43.7%]), lack of efficacy (n = 144 [24.3%]), lack of compliance (n = 138 [23.3%]), and lack of tolerability (n = 52 [8.8%]) with the previous oral antipsychotic medication. The recommended PP initiation regimen (150 milligram equivalents [mg eq] day 1 and 100 mg eq day 8) was administered in 93.9% of patients. Mean PANSS total score decreased from 71.5 (14.6) at baseline to 59.7 (18.1) at end point (mean change, -11.7 [15.9]; 95% CI, -13.0 to -10.5; P < 0.0001). Sixty-four percent of patients showed an improvement of ≥20% in PANSS total score, and the percentage of patients rated mildly ill or less in Clinical Global Impression-Severity increased from 31.8% to 63.2%. Mean personal and social performance total score (SD) increased

  10. Allopurinol for mania: a randomized trial of allopurinol versus placebo as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder.

    Science.gov (United States)

    Weiser, Mark; Burshtein, Shimon; Gershon, Ari A; Marian, Gabriela; Vlad, Nicolae; Grecu, Iosif G; Tocari, Elena; Tiugan, Alexandru; Hotineanu, Mihail; Davis, John M

    2014-06-01

    An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists; there is a well-characterized interaction between adenosine and dopamine receptors in the ventral striatum, and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. Allopurinol increases adenosine levels in the brain, and hence is hypothesized to reduce the symptoms of mania. Two randomized, placebo-controlled trials administering add-on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale (YMRS) scores for drug compared to placebo, while a more recent, relatively small, add-on study showed negative results. Based on these data, our objective was to examine the efficacy of allopurinol as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder. We performed a large, well-powered, multicenter, six-week, randomized, placebo-controlled trial of allopurinol added to mood stabilizers and/or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode. Both groups showed improvement on the YMRS (effect size of 1.5 for placebo and 1.6 for allopurinol), with no difference observed between groups on YMRS scores (t = 0.28, p = 0.78). There was no difference in the proportion of patients who responded to treatment (defined as showing at least 50% improvement in YMRS score) between the two groups (p = 0.92), or in dropout rates (p = 0.84). None of our patients received lithium. However, the side effects of lithium and its narrow therapeutic index made the use of lithium less common and, therefore, our study results reflect common current clinical practice. In the present study, we used a variety of antipsychotic and/or mood stabilizing treatments, to which we added allopurinol; one

  11. Antipsychotic Use in Dementia

    Science.gov (United States)

    Kirkham, Julia; Sherman, Chelsea; Velkers, Clive; Maxwell, Colleen; Gill, Sudeep; Rochon, Paula

    2016-01-01

    Antipsychotics are necessary for many older adults to treat major mental illnesses or reduce distressing psychiatric symptoms. Current controversy exists over the role of antipsychotics in the management of neuropsychiatric symptoms (NPS) in persons with dementia. Although some NPS may be appropriately and safely treated with antipsychotics, a fine balance must be achieved between the benefits of these medications, which are often modest, and adverse events, which may have significant consequences. Approximately one-third of all persons with dementia are currently prescribed antipsychotic medications, and there is significant variation in the use of antipsychotics across care settings and providers. Reducing the inappropriate or unnecessary use of antipsychotics among persons with dementia has been the focus of increasing attention owing to better awareness of the potential problems associated with these medications. Several approaches can be used to curb the use of antipsychotics among persons with dementia, including policy or regulatory changes, public reporting, and educational outreach. Recently, there has been encouraging evidence of a downward trend in the use of antipsychotics in many long-term care settings, although prescribing rates are still higher than what is likely optimal. Although reducing the inappropriate use of antipsychotics is a complex task, psychiatrists can play an important role via the provision of clinical care and research evidence, contributing to improved care of persons with dementia in Canada and elsewhere. PMID:28212496

  12. FTBMT, a Novel and Selective GPR52 Agonist, Demonstrates Antipsychotic-Like and Procognitive Effects in Rodents, Revealing a Potential Therapeutic Agent for Schizophrenia.

    Science.gov (United States)

    Nishiyama, Keiji; Suzuki, Hirobumi; Harasawa, Toshiya; Suzuki, Noriko; Kurimoto, Emi; Kawai, Takayuki; Maruyama, Minoru; Komatsu, Hidetoshi; Sakuma, Kensuke; Shimizu, Yuji; Shimojo, Masato

    2017-11-01

    GPR52 is a Gs-coupled G protein-coupled receptor that is predominantly expressed in the striatum and nucleus accumbens (NAc) and was recently proposed as a potential therapeutic target for schizophrenia. In the current study, we investigated the in vitro and in vivo pharmacologic activities of a novel GPR52 agonist, 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1 H -1,2,4-triazol-1-yl)-2-methylbenzamide (FTBMT). FTBMT functioned as a selective GPR52 agonist in vitro and in vivo, as demonstrated by the activation of Camp signaling in striatal neurons. FTBMT inhibited MK-801-induced hyperactivity, an animal model for acute psychosis, without causing catalepsy in mice. The c-fos expression also revealed that FTBMT preferentially induced neuronal activation in the shell of the Nac compared with the striatum, thereby supporting its antipsychotic-like activity with less catalepsy. Furthermore, FTBMT improved recognition memory in a novel object-recognition test and attenuated MK-801-induced working memory deficits in a radial arm maze test in rats. These recognitive effects were supported by the results of FTBMT-induced c-fos expression in the brain regions related to cognition, including the medial prefrontal cortex, entorhinal cortex, and hippocampus. Taken together, these findings suggest that FTBMT shows antipsychotic and recognitive properties without causing catalepsy in rodents. Given its unique pharmacologic profile, which differs from that of current antipsychotics, FTBMT may provide a new therapeutic option for the treatment of positive and cognitive symptoms of schizophrenia. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Long-term effectiveness of flexibly dosed paliperidone extended-release: comparison among patients with schizophrenia switching from risperidone and other antipsychotic agents.

    Science.gov (United States)

    Kim, Eun Young; Chang, Sung Man; Shim, Joo Cheol; Joo, Eun Jeong; Kim, Jae Jin; Kim, Yong Sik; Ahn, Yong Min

    2013-10-01

    The current study compared the long-term effectiveness, safety, and tolerability of paliperidone extended-release (ER) among patients with schizophrenia who had switched from risperidone (risperidone group) or other antipsychotic medications (non-risperidone group) due to lack of efficacy, intolerability, or non-adherence. This open-label, prospective, multicenter, 48 week study utilized the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity scale (CGI-S), the Personal and Social Performance scale (PSP), and the Subjective Well-being under Neuroleptics scale (SWN) to assess patients with schizophrenia. Additionally, extrapyramidal symptoms (EPS) and subjective side effects were evaluated with validated scales. Clinicaltrials.gov identifier: NCT00864045. The completion rate for this study was 51.6% (95/184), and 169 patients finished with ≥1 post-baseline assessment (81 patients in the risperidone group, 88 in the non-risperidone group). The mean (SD) PANSS total score decreased significantly from 78.3 (18.8) to 65.5 (19.7) in the risperidone group and from 79.1 (19.8) to 65.4 (20.8) in the other group (all p antipsychotic treatments to paliperidone ER can be a useful option to achieve long-term improvement in symptoms and functioning for patients with schizophrenia. The clinical effectiveness appeared to be similar in patients who previously received risperidone and those treated with other antipsychotic medications. The open-label design and lack of a placebo group were limitations.

  14. Effects of Controlled Discontinuation of Long-Term Used Antipsychotics on Weight and Metabolic Parameters in Individuals With Intellectual Disability

    NARCIS (Netherlands)

    de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Visser, Frank; Hoekstra, Pieter J.

    Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of

  15. 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

  16. Evidence for the hERG Liability of Antihistamines, Antipsychotics, and Anti-Infective Agents: A Systematic Literature Review From the ARITMO Project.

    Science.gov (United States)

    Hazell, Lorna; Raschi, Emanuel; De Ponti, Fabrizio; Thomas, Simon H L; Salvo, Francesco; Ahlberg Helgee, Ernst; Boyer, Scott; Sturkenboom, Miriam; Shakir, Saad

    2017-05-01

    A systematic review was performed to categorize the hERG (human ether-a-go-go-related gene) liability of antihistamines, antipsychotics, and anti-infectives and to compare it with current clinical risk of torsade de pointes (TdP). Eligible studies were hERG assays reporting half-minimal inhibitory concentrations (IC50). A "hERG safety margin" was calculated from the IC50 divided by the peak human plasma concentration (free C max ). A margin below 30 defined hERG liability. Each drug was assigned an "uncertainty score" based on volume, consistency, precision, and internal and external validity of evidence. The hERG liability was compared to existing knowledge on TdP risk (www.credibledrugs.org). Of 1828 studies, 82 were eligible, allowing calculation of safety margins for 61 drugs. Thirty-one drugs (51%) had evidence of hERG liability including 6 with no previous mention of TdP risk (eg, desloratadine, lopinavir). Conversely, 16 drugs (26%) had no evidence of hERG liability including 6 with known, or at least conditional or possible, TdP risk (eg, chlorpromazine, sulpiride). The main sources of uncertainty were the validity of the experimental conditions used (antihistamines and antipsychotics) and nonuse of reference compounds (anti-infectives). In summary, hERG liability was categorized for 3 widely used drug classes, incorporating a qualitative assessment of the strength of available evidence. Some concordance with TdP risk was observed, although several drugs had hERG liability without evidence of clinical risk and vice versa. This may be due to gaps in clinical evidence, limitations of hERG/C max data, or other patient/drug-specific factors that contribute to real-life TdP risk. © 2016, The American College of Clinical Pharmacology.

  17. 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...

  18. Antipsychotic-induced Hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    Suheyla Dogan Bulut

    2015-06-01

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

  19. Effect of GWAS-Identified Genetic Variants on Maximum QT Interval in Patients With Schizophrenia Receiving Antipsychotic Agents: A 24-Hour Holter ECG Study.

    Science.gov (United States)

    Watanabe, Junzo; Fukui, Naoki; Suzuki, Yutaro; Sugai, Takuro; Ono, Shin; Tsuneyama, Nobuto; Saito, Mami; Tajiri, Misuzu; Someya, Toshiyuki

    2017-08-01

    Users of antipsychotics (APs) have a risk of sudden cardiac death (SCD). Sudden cardiac death in such patients is thought to be largely due to drug-induced QT prolongation. It has been reported that many subjects with drug-induced torsades de pointes (TdP) have risk alleles associated with subclinical congenital long QT syndrome. We investigated the effects of the risk alleles associated with long QT on the QT interval in patients receiving APs using 24-hour Holter electrocardiograms to take into account the circadian fluctuation of QT intervals. We investigated 8 single-nucleotide polymorphisms identified on a GWAS. We found that increased numbers of risk alleles at rs7188697 in NDRG4 and rs11970286 in PLN were the major predictors of an increased maximum QT interval over 24 hours in users of APs. It could be useful to perform a DNA-based analysis before the initiation of APs to reduce the risk of drug-induced torsades de pointes and SCD.

  20. Economic evaluations of novel antipsychotic medications: a literature review.

    Science.gov (United States)

    Hudson, Teresa J; Sullivan, Greer; Feng, Weiwei; Owen, Richard R; Thrush, Carol R

    2003-04-01

    To evaluate the evidence that novel antipsychotic medications offer a cost advantage compared to traditional antipsychotic medications. Literature for this review was identified through a computerized search of Medline, Healthstar and Psyc-INFO databases inclusive from January 1989 to January 2002. Articles included in the review were required to include cost evaluation and to be published in peer-reviewed journals. Twenty-two studies met inclusion criteria. All five studies that used experimental designs found that second-generation antipsychotic medications were associated with a cost advantage or were cost-neutral, and, in some cases, improved quality of life. Of the ten studies using a pre-post design, four found an increase in total costs, six reported a decrease in total costs, and four reported increased effectiveness with use of a second-generation antipsychotic. All seven of the simulation studies reported a cost advantage for novel antipsychotics for specific patient populations under certain conditions. The majority of studies found that novel antipsychotics are at least cost-neutral and may offer cost advantages compared to traditional agents. Some studies also reported greater improvement in effectiveness and quality of life when novel antipsychotics were compared to traditional antipsychotic medications. However, it is difficult to draw firm conclusions given the small sample sizes and limited study designs available in this literature.

  1. 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.

  2. 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

  3. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    Directory of Open Access Journals (Sweden)

    Nevena Divac

    2014-01-01

    Full Text Available Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest, high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.

  4. Antipsychotic treatment is associated with risk of atrial fibrillation: A nationwide nested case-control study.

    Science.gov (United States)

    Chou, Ruey-Hsing; Lo, Li-Wei; Liou, Ying-Jay; Shu, Jiah-Hwang; Hsu, Hsiu-Chuan; Liang, Ying; Huang, Chin-Chou; Huang, Po-Hsun; Lin, Shing-Jong; Chen, Jaw-Wen; Chan, Wan-Leong; Leu, Hsin-Bang

    2017-01-15

    Antipsychotic agents are well known for their arrhythmigenic effect on ventricular arrhythmia. Though a few case reports observed the occurrence of atrial fibrillation (AF) after antipsychotic exposure, information about their implication in AF is limited. Based on the National Health Insurance Database in Taiwan, we conducted a nested case-control study to investigate the relationship between antipsychotics and AF. From 2001 to 2010, a total of 34,053 cases of AF and 34,919 matched controls were enrolled. Antipsychotic exposure was measured and binding affinity to neurotransmitter receptors was calculated. Both medical and psychiatric comorbidities were identified and adjusted in multivariate logistic regression analysis. Current antipsychotic use was associated with a 17% increased risk of AF relative to nonusers (adjusted OR: 1.17, 95% CI: 1.10-1.26). A dose-dependent relationship of antipsychotic exposure and AF risk was observed (P for trend Antipsychotics with higher binding affinity to muscarinic M2 receptors were associated with a higher incidence of AF. In subgroup analysis, subjects with preexisting hypertension, diabetes, or coronary artery diseases were at greater risk of developing AF following antipsychotic exposure. Antipsychotic exposure was associated with increased risk of AF, especially for agents with higher cardiac muscarinic receptor binding affinity. Physicians should monitor the occurrence of new-onset AF, and strictly control underlying medical risk factors while prescribing antipsychotic agents to high-risk populations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. 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.

  6. Atypical antipsychotic therapy in Parkinson's disease psychosis: A retrospective study

    OpenAIRE

    Yuan, Mei; Sperry, Laura; Malhado?Chang, Norika; Duffy, Alexandra; Wheelock, Vicki; Farias, Sarah; O'Connor, Kevin; Olichney, John; Shahlaie, Kiarash; Zhang, Lin

    2017-01-01

    Abstract Objective Parkinson's disease psychosis (PDP) is a frequent complication of idiopathic Parkinson's disease (iPD) with significant impact on quality of life and association with poorer outcomes. Atypical antipsychotic drugs (APDs) are often used for the treatment of PDP; however, their use is often complicated by adverse drug reactions (ADRs). In this study, we present patients with PDP who were treated with the most commonly used atypical antipsychotic agents and review their respect...

  7. Validation of a claims-based antipsychotic polypharmacy measure†

    Science.gov (United States)

    Leckman-Westin, Emily; Kealey, Edith; Gupta, Nitin; Chen, Qingxian; Gerhard, Tobias; Crystal, Stephen; Olfson, Mark; Finnerty, Molly

    2015-01-01

    Purpose Given the metabolic and neurologic side effects of antipsychotics and concerns about the increased risks associated with concomitant use, antipsychotic polypharmacy is a quality concern. This study assessed the operating characteristics of a Medicaid claims-based measure of antipsychotic polypharmacy. Methods A random sample from 10 public mental health clinics and 312 patients met criteria for this study. Medical record extractors were blind to measure status. We examined the prevalence, sensitivity, specificity, and positive predictive value (PPV) in Medicaid claims, testing nine different definitions of antipsychotic polypharmacy, including >14, >60, or >90 days concurrent use of ≥2 antipsychotic agents, each with allowable gaps of up to 0, 14, or 32 days in days’ supply of antipsychotic medications. Results All Medicaid claims measure definitions tested had excellent specificity and PPV (>91%). Good to excellent sensitivity was dependent upon use of a 32-day gap allowance, particularly as duration of concurrent antipsychotic use increased. The proposed claims-based measure (90-day concurrent use of ≥2 or more antipsychotics, allowing for a 32-day gap) had excellent specificity (99.1%, 95%CI: 98.2–99.6) and PPV (90.9%, 95%CI: 83.1–95.7) with good sensitivity (79.4%, 95%CI: 70.4–86.6). The overall level of concordance between claims and medical record-based categorization of antipsychotic polypharmacy was high (96.4%, n = 301/312 clients, Cohen's K = 84.7, 95%CI: 75.9–93.5). Discrepant cases were reviewed, and implications are discussed. Conclusions Administrative claims data can be used to construct valid measures of antipsychotic polypharmacy. PMID:24664793

  8. Design, synthesis, and preliminary in vitro and in vivo pharmacological evaluation of 2-{4-[4-(2,5-disubstituted thiazol-4-yl)phenylethyl]piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles as atypical antipsychotic agents.

    Science.gov (United States)

    Gowri Chandra Sekhar, Kondapalli Venkata; Rao, Vajja Samabasiva; Deuther-Conrad, Winnie; Reddy, Aravalli Satish; Brust, Peter; Krishna Kumar, Mutyala Murali

    2011-08-01

    A series of 2-{4-[4-(2,5-disubstituted thiazolyl)phenylethyl] piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized either by microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. The D(2) and 5-HT(2A) affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. The D(2) antagonism studies were performed using climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 10f is the most active among the synthesized compounds with 5-HT(2A)/D(2) ratio of 1.1286 although the standard drug risperidone exhibited 5-HT(2A)/D(2) ratio of 1.0989.

  9. Atypical antipsychotic use and outcomes in an urban maternal mental health service.

    Science.gov (United States)

    Hatters Friedman, Susan; Moller-Olsen, Charmian; Prakash, Chandni; North, Abigail

    2016-08-01

    Objective Despite many women suffering from psychosis in their childbearing years, limited data exist about the use of atypical antipsychotic agents in pregnancy. Atypical antipsychotic agents are often used to treat bipolar disorder, instead of lithium or valproate because of the known teratogenicity of those agents. As well, atypical antipsychotics are often prescribed in anxiety disorders and depression. This study sought to describe pregnancy outcomes for women prescribed atypical antipsychotics during pregnancy. Methods This retrospective review included all cases treated by Auckland Maternal Mental Health services in which atypical antipsychotic agents were utilized during pregnancy over three years. Results Over the three years, 45 pregnant women were prescribed atypical antipsychotic agents, most commonly quetiapine or olanzapine. Two-fifths (40%) were diagnosed with bipolar disorder and almost one-third (31%) with a psychotic disorder. Two-thirds (64%) were prescribed multiple psychotropic medications during their pregnancy. Instrumental delivery rates were elevated at 38%. A minority (13%) of the women developed gestational diabetes mellitus. Although 7% of infants were born premature, all were born after 35 weeks. Two major malformations were noted, similar to baseline community rates. Conclusions This naturalistic study adds to the limited literature about treatment with atypical antipsychotic agents in pregnancy, though not adequately powered to detect small differences in malformations or obstetrical outcomes. It also highlights the myriad of indications for which pregnant women are prescribed atypical antipsychotics, and the multiple other risk factors seen in this population.

  10. Nphenylacetamides: Potential Antipsychotics

    African Journals Online (AJOL)

    Purpose: Arylpiperazines have been recognized as the largest and most diverse class of compounds exerting actions on the central nervous system with strong affinity for serotonin and dopamine receptors. We here report the synthesis of some novel arylpiperazines and their evaluation for possible antipsychotic properties.

  11. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Arlan L. Rosenbloom

    2010-01-01

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

  12. Predictors of switching antipsychotic medications in the treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Stauffer Virginia L

    2010-09-01

    Full Text Available Abstract Background To identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia. Methods This post-hoc analysis used data from a one-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted after the first eight weeks. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first two weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication. Results About one-third of patients (29.5%, 191/648 switched antipsychotics before the end of the one-year study. There were six variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale, and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale during the first two weeks of antipsychotic therapy. Conclusions Switching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following two weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics.

  13. Predictors of switching antipsychotic medications in the treatment of schizophrenia.

    Science.gov (United States)

    Nyhuis, Allen W; Faries, Douglas E; Ascher-Svanum, Haya; Stauffer, Virginia L; Kinon, Bruce J

    2010-09-28

    To identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia. This post-hoc analysis used data from a one-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted after the first eight weeks. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first two weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication. About one-third of patients (29.5%, 191/648) switched antipsychotics before the end of the one-year study. There were six variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale), and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale) during the first two weeks of antipsychotic therapy. Switching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following two weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics.

  14. O impacto dos agentes antipsicóticos na densidade mineral óssea de pacientes esquizofrênicos Impact of antipsychotic agents in bone mineral density of schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Lísia Rejane Guimarães

    2006-12-01

    Full Text Available Estudos têm evidenciado o alto risco de osteoporose em pacientes esquizofrênicos. Alguns estudos têm demonstrado que os neurolépticos típicos e a risperidona podem induzir a osteoporose ou reduzir a densidade mineral óssea. Isso pode ser atribuído ao fato de estas drogas, em uso prolongado, induzirem a hiperprolactinemia a níveis acima do normal, em ambos os sexos, e a baixa dos níveis de estrogênio e de testosterona, aumentando o risco para osteopenia/osteoporose. Neste relato, será apresentado um caso de osteopenia em uma paciente mulher de 53 anos, em uso de antipsicóticos há 30 anos, sendo comentados os procedimentos recomendados para detecção dessa ocorrência e as diretrizes existentes para seu manejo.Studies have shown a high risk of osteoporosis in schizophrenic patients. Some studies have demonstrated that typical neuroleptics and risperidone may induce osteoporosis or reduce bone mineral density. This can be due to the fact that prolonged use of those drugs induces hyperprolactinemia to levels above normal in both genders, and reduces the levels of estrogen and testosterone, thus increasing the risk of osteopenia/osteoporosis. We report on a case of osteopenia in a 53-year-old female patient using antipsychotics for 30 years. We comment on the recommended procedures to detect osteopenia and on the existing guidelines for its management.

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

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

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

  16. 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

  17. Conformance to schizophrenia treatment guidelines in North West-Bank, Palestine: focus on antipsychotic dosing and polytherapy

    Science.gov (United States)

    2013-01-01

    Background Analysis of the prescribing patterns of antipsychotic drugs can improve therapeutic outcomes. The purpose of this study was to evaluate the prescribing pattern of antipsychotics and its conformance to international treatment guidelines. Methods A cross sectional study at primary psychiatric centers was carried out. Patients’ medical files were used to obtain demographic, medication and clinical information. International guidelines for schizophrenia were used to create conformance indicators. All statistical analyses were conducted using Statistical Package for Social Sciences. Results 250 patients were included in this study. A total of 406 antipsychotic agents were used; 348 (85.7%) were first generation antipsychotics (FGA). The prevalence of antipsychotic combination was 50.4% (n=126). There was no significant difference in positive (p=0.3), negative (p=0.06) and psychopathology (p=0.5) scores of schizophrenia symptoms among patients on monotherapy versus those on antipsychotic combination. Furthermore, no significant difference was observed in the annual cost of antipsychotic monotherapy versus combination therapy. One hundred and five patients (42%) were using optimum dose of (300 – 600 mg CPZeq) while the remaining were using sub or supra therapeutic doses. Analysis showed that use of depot, use of anticholinergic agents and increasing amount of total CPZeq were significant factors associated with antipsychotic combination. Conclusions This study indicated that antipsychotic prescribing was not in conformance with international guidelines with respect to maintenance dose and combination therapy. Type of antipsychotic treatment regimen, combination versus monotherapy, was not associated with better clinical or economic outcome. PMID:23816223

  18. The Harms of Antipsychotic Drugs: Evidence from Key Studies.

    Science.gov (United States)

    Moore, Thomas J; Furberg, Curt D

    2017-01-01

    This safety assessment provides a detailed analysis of key studies and focuses on the six most widely used antipsychotic drugs. Lines of evidence include mechanisms of action, short-term treatment of psychosis, relapse prevention, early intervention in schizophrenia, long-term comparisons between first- and second-generation agents, and flexible treatment algorithms. Despite the diversity of study settings, several common features were seen. All the agents obstruct normal signaling through widely dispersed dopamine D 2 receptors. Treatment failure or psychosis relapse was the most frequent outcome in most key studies, ranging from 38 to 93%. High discontinuation rates caused most trials to fail to demonstrate a substantial treatment benefit, or difference from an active comparator. Assessment of harm to the extrapyramidal motor system was confounded because of extensive neurological impairment from previous antipsychotic drug treatment measured at baseline, abrupt discontinuation effects, and high rates of concomitant medications to manage drug adverse effects. Claims that second-generation antipsychotic drugs have safety advantages over classical neuroleptic drugs and prevent relapse were not supported in these key studies. The extent of injury to and impairment of multiple body systems caused by antipsychotic drugs shows the need for a scientific, clinical, and regulatory reappraisal of the appropriate use of these agents.

  19. Pharmacological treatment for antipsychotic-related constipation.

    Science.gov (United States)

    Every-Palmer, Susanna; Newton-Howes, Giles; Clarke, Mike J

    2017-01-24

    Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population. An understanding of the effectiveness and safety of treatment for antipsychotic-related constipation is important for clinicians and patients alike. To evaluate the effectiveness and safety of pharmacologic treatment (versus placebo or compared against another treatment) for antipsychotic-related constipation (defined as constipated patients of any age, who are treated with antipsychotics, regardless of dose, in which constipation is considered to be an antipsychotic-related side effect). We searched the Cochrane Schizophrenia Group's Trials Register (15 June 2015), which is based on regular searches of MEDLINE, Embase, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records in this register. We also handsearched bibliographies and contacted relevant authors for additional information. We included all published and unpublished randomised controlled trials (RCTs) investigating the efficacy of pharmacological treatments in patients with antipsychotic-related constipation. Pharmacological treatments included laxatives and other medicines that could reasonably be used to combat constipation in this population (e.g. anticholinergic agents, like bethanecol). Two review authors independently extracted data from all included studies and assessed trials for risk of bias. A third author reviewed

  20. Atypical antipsychotics in the elderly.

    Science.gov (United States)

    Beck Carol Paton Rafael Euba Cait Goddard, S

    2001-01-01

    Although their primary purpose is to treat psychosis, antipsychotics are commonly prescribed for the elderly to treat the behavioural disturbances and agitation associated with dementia. Such use is controversial. Atypical antipsychotics cause fewer extrapyramidal sideeffects than the older drugs in younger adults, but the evidence base for their efficacy and tolerability in the elderly is poor. The aims of this study were to determine the prevalence of atypical antipsychotic prescribing for the elderly, the indications for use and documented side-effects. The medication cards of all patients from 19 Trusts, occupying a psychiatric bed for the over 65s, were screened during one week in March 2000. Data were collected by pharmacists from the clinical notes. Half of those prescribed an antipsychotic received an atypical, and risperidone was the one most commonly prescribed. Half the sample had a diagnosis of dementia. Documented side-effects from the atypical were uncommon. Atypicals are frequently prescribed as first-line antipsychotics for behavioural problems associated with dementia, despite the poor evidence base for their efficacy and safety in this population. Undermonitoring of side-effects may remain a problem.

  1. Long-Term Antipsychotic Polypharmacy in the VA Health System: Patient Characteristics and Treatment Patterns

    Science.gov (United States)

    Kreyenbuhl, Julie A.; Valenstein, Marcia; McCarthy, John F.; Ganoczy, Dara; Blow, Frederic C.

    2011-01-01

    Objective Although antipsychotic polypharmacy is being prescribed with increasing frequency, few studies have described patient characteristics and treatment patterns associated with long-term use of this treatment strategy. Methods By using data from the National Psychosis Registry of the Department of Veterans Affairs, 5,826 patients with schizophrenia or schizoaffective disorder who received long-term antipsychotic polypharmacy (simultaneous treatment with two or more antipsychotics for 90 or more days) during fiscal year 2000 and 39,745 patients who received long-term antipsychotic monotherapy were identified. By using multivariate regression models, patient demographic and clinical characteristics, antipsychotic dosages, and use of antiparkinson and adjunctive psychotropic medications were compared between the two groups. Results Patients were more likely to receive antipsychotic polypharmacy if they were younger, were unmarried, had a military service–connected disability, had schizophrenia rather than schizoaffective disorder, or had greater use of inpatient and outpatient mental health services. Patients were less likely to receive antipsychotic polypharmacy if they were African American, had concurrent diagnoses of depression or substance use disorder, or had greater medical comorbidity. For most antipsychotics, dosages prescribed for patients receiving polypharmacy were the same or modestly higher than those prescribed for patients receiving monotherapy. Patients given prescriptions for polypharmacy were more likely to receive antiparkinson medications, antianxiety agents, and mood stabilizers and equally likely to receive concurrent treatment with antidepressants. Conclusions Long-term antipsychotic polypharmacy appears to be reserved for more severely ill patients with psychotic symptoms rather than mood symptoms. These patients may experience increased adverse effects as a result of excess antipsychotic exposure. PMID:17412850

  2. Establishment of the National Pregnancy Registry for Atypical Antipsychotics.

    Science.gov (United States)

    Cohen, Lee S; Viguera, Adele C; McInerney, Kathryn A; Kwiatkowski, Molly A; Murphy, Shannon K; Lemon, Elizabeth L; Hernández-Díaz, Sonia

    2015-07-01

    Atypical antipsychotics are widely used by reproductive-age women to treat a spectrum of psychiatric illnesses. Despite widespread use of this class of agents in women of childbearing potential, reproductive safety data across these medicines remain limited. The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) at Massachusetts General Hospital was established in 2008 to address this knowledge gap. Data are prospectively collected from pregnant women, ages 18-45 years, using 3 phone interviews conducted at the following times: (1) proximate to the time of enrollment, (2) 7 months' gestation, and (3) 2-3 months postpartum. Subjects include pregnant women with histories of fetal exposure to second-generation antipsychotics and a comparison group of nonexposed pregnant women. Medical record release authorization is obtained for obstetric, labor and delivery, and newborn pediatric (up to 6 months of age) records. Information regarding the presence of major malformations is abstracted from the medical records along with other data regarding neonatal and maternal health outcomes. Identified cases of congenital malformations are sent to a dysmorphologist blinded to drug exposure for final adjudication. As of May 2014, 428 subjects have enrolled in the NPRAA. Efforts continue to increase enrollment for the purpose of enhancing the capacity to define risk estimates of in utero exposure to atypical antipsychotics. The NPRAA gathers prospective data regarding risk for critical outcomes following use of atypical antipsychotics during pregnancy. The NPRAA offers a systematic way to collect reproductive safety information that informs the care of women who use these agents to sustain psychiatric well-being. ClinicalTrials.gov identifier: NCT01246765. © Copyright 2015 Physicians Postgraduate Press, Inc.

  3. [Clinically relevant drug interactions with new generation antidepressants and antipsychotics].

    Science.gov (United States)

    Eckert, Anne

    2009-06-01

    Because antidepressants and antipsychotics are commonly described in combination with drugs used to treat comorbid psychiatric or somatic disorders (e.g. anxiolytics, mood stabilizers, cardiovascular drugs, antimicrobial agents), they may be involved in drug interactions. Furthermore, agents such as lithium and atypical antipsychotics may be used to augment the antidepressant response in cases of refractory depression. Based on their mechanisms, drug-drug interactions can be classified either as pharmacokinetic or pharmacodynamic in nature. The well-documented risk of potentially harmful pharmacodynamic drug interactions with first-generation anti-depressants, e.g. monoamine oxidase inhibitors (MAOIs), with regard to the induction of the serotonin syndrome, has contributed to a gradual decline in their use in clinical practise. Second- and third-generation antidepressants have gradually replaced tricyclic antidepressants (TCAs) and MAOIs, mainly because of their improved tolerability and safety profile. The second- and third-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and other compounds with different mechanisms of action. These drugs and also the majority of antipsychotics are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Therefore, the use of these compounds may be associated with clinically relevant pharmacokinetic interactions with other medications. The knowledge about the CYP metabolism of drugs may be used to guide the selection of an antidepressant or an anti-psychotic with a low drug-drug interaction potential for an individual patient. The aim of the present article is to review drug-interaction potentials with specific focus on second-generation antidepressants (SSRIs), newer antidepressants (SNRIs: venlafaxine and duloxetine; bupropion, mirtazapine, trazodone), novel atypical antidepressants (agomelatine), as well as new generation

  4. New users of antipsychotic medication

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    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...... 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...

  5. Diabetic control and atypical antipsychotics: a case report

    Directory of Open Access Journals (Sweden)

    Gaston Romina

    2008-05-01

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

  6. Antipsychotic drugs and risks of myocardial infarction: a self-controlled case series study.

    Science.gov (United States)

    Brauer, Ruth; Smeeth, Liam; Anaya-Izquierdo, Karim; Timmis, Adam; Denaxas, Spiros C; Farrington, C Paddy; Whitaker, Heather; Hemingway, Harry; Douglas, Ian

    2015-04-21

    Antipsychotics increase the risk of stroke. Their effect on myocardial infarction remains uncertain because people prescribed and not prescribed antipsychotic drugs differ in their underlying vascular risk making between-person comparisons difficult to interpret. The aim of our study was to investigate this association using the self-controlled case series design that eliminates between-person confounding effects. All the patients with a first recorded myocardial infarction and prescription for an antipsychotic identified in the Clinical Practice Research Datalink linked to the Myocardial Ischaemia National Audit Project were selected for the self-controlled case series. The incidence ratio of myocardial infarction during risk periods following the initiation of antipsychotic use relative to unexposed periods was estimated within individuals. A classical case-control study was undertaken for comparative purposes comparing antipsychotic exposure among cases and matched controls. We identified 1546 exposed cases for the self-controlled case series and found evidence of an association during the first 30 days after the first prescription of an antipsychotic, for first-generation agents [incidence rate ratio (IRR) 2.82, 95% confidence interval (CI) 2.0-3.99] and second-generation agents (IRR: 2.5, 95% CI: 1.18-5.32). Similar results were found for the case-control study for new users of first- (OR: 3.19, 95% CI: 1.9-5.37) and second-generation agents (OR: 2.55, 95% CI: 0.93-7.01) within 30 days of their myocardial infarction. We found an increased risk of myocardial infarction in the period following the initiation of antipsychotics that was not attributable to differences between people prescribed and not prescribed antipsychotics. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  7. Some novelties and recommendations by swithing antipsychotics

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    Nika Aleksandra Kravos

    2014-11-01

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

  8. [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

  9. Minimizing weight gain for patients taking antipsychotic medications: The potential role for early use of metformin.

    Science.gov (United States)

    Hendrick, Victoria; Dasher, Robert; Gitlin, Michael; Parsi, Mehrban

    2017-05-01

    Patients taking antipsychotic medications are at high risk for weight gain, which in turn leads to poor health outcomes, nonadherence with treatment, and low self-esteem. We reviewed published studies of pharmacologic interventions aimed at minimizing antipsychotic-induced weight gain. Treatments initiated prior to onset of weight gain were compared with those that started once weight gain already had occurred. Although data are limited, adjunctive medications for weight management appear to be more effective when initiated at or near the time when patients are first exposed to antipsychotic medications. Interventions initiated later in the course of treatment-typically after weight gain already has occurred-rarely help patients return to their pretreatment weight. The most commonly used adjunctive intervention has been metformin. Certain patients benefit from initiating metformin early in their exposure to second-generation antipsychotic agents. In particular, young, healthy patients beginning olanzapine or clozapine probably will experience less weight gain if they concomitantly initiate metformin.

  10. Clinical and economic ramifications of switching antipsychotics in the treatment of schizophrenia.

    Science.gov (United States)

    Faries, Douglas E; Ascher-Svanum, Haya; Nyhuis, Allen W; Kinon, Bruce J

    2009-09-02

    Switching between antipsychotic medications is common in the treatment of schizophrenia. However, data on clinical and economic outcomes from antipsychotic switching, in particular acute care service use, is fairly limited. The goal of this research was to assess the clinical and economic ramifications of switching antipsychotics during outpatient management of schizophrenia. Data from a 1-year randomized, open-label cost-effectiveness study involving typical and atypical antipsychotics were assessed. The study protocol permitted switching of antipsychotics when clinically warranted. The risk of crisis-related events, use of acute-care services, and the time to the initial use of such services were determined in outpatients who switched antipsychotics compared with those who continued with their initial medications. Health care resource utilization data were abstracted from medical records and other sources (e.g., patient self-report), and direct costs were estimated using previously published benchmarks. Almost one-third of patients (29.3%) underwent a switch from their initial antipsychotic agent, with an average duration of 100 days before such treatment alterations. Compared with their counterparts who remained on their initial therapies, individuals who switched antipsychotics experienced a significantly higher risk of acute-care services, including hospitalization (p = .013) and crisis services (p = .011). Patients undergoing medication switches also used acute-care services significantly sooner (p = .004) and accrued an additional $3,000 (a 25% increase) in annual total health care costs per patient, most of which was due to acute-care expenditures. Switching antipsychotic medications was found to be associated with considerably poorer clinical and economic outcomes, as reflected by, more frequent and more rapid use of acute-care services compared with persons remaining on their initial treatments. Trial ID 2325 in LillyTrials.com (also accessible via

  11. Clinical and economic ramifications of switching antipsychotics in the treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Nyhuis Allen W

    2009-09-01

    Full Text Available Abstract Background Switching between antipsychotic medications is common in the treatment of schizophrenia. However, data on clinical and economic outcomes from antipsychotic switching, in particular acute care service use, is fairly limited. The goal of this research was to assess the clinical and economic ramifications of switching antipsychotics during outpatient management of schizophrenia. Methods Data from a 1-year randomized, open-label cost-effectiveness study involving typical and atypical antipsychotics were assessed. The study protocol permitted switching of antipsychotics when clinically warranted. The risk of crisis-related events, use of acute-care services, and the time to the initial use of such services were determined in outpatients who switched antipsychotics compared with those who continued with their initial medications. Health care resource utilization data were abstracted from medical records and other sources (e.g., patient self-report, and direct costs were estimated using previously published benchmarks. Results Almost one-third of patients (29.3% underwent a switch from their initial antipsychotic agent, with an average duration of 100 days before such treatment alterations. Compared with their counterparts who remained on their initial therapies, individuals who switched antipsychotics experienced a significantly higher risk of acute-care services, including hospitalization (p = .013 and crisis services (p = .011. Patients undergoing medication switches also used acute-care services significantly sooner (p = .004 and accrued an additional $3,000 (a 25% increase in annual total health care costs per patient, most of which was due to acute-care expenditures. Conclusion Switching antipsychotic medications was found to be associated with considerably poorer clinical and economic outcomes, as reflected by, more frequent and more rapid use of acute-care services compared with persons remaining on their initial treatments

  12. Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D(1), D(2) and serotonin 5-HT(1A) multi-action profile.

    Science.gov (United States)

    Sun, Haifeng; Zhu, Liyuan; Yang, Huicui; Qian, Wangke; Guo, Lin; Zhou, Shengbin; Gao, Bo; Li, Zeng; Zhou, Yu; Jiang, Hualiang; Chen, Kaixian; Zhen, Xuechu; Liu, Hong

    2013-02-15

    An effective and rapid method for the microwave-assisted preparation of the key intermediate for the total synthesis of tetrahydroprotoberberines (THPBs) including l-stepholidine (l-SPD) was developed. Thirty-one THPB derivatives with diverse substituents on A and D ring were synthesized, and their binding affinity to dopamine D(1), D(2) and serotonin 5-HT(1A) and 5-HT(2A) receptors were determined. Compounds 18k and 18m were identified as partial agonists at the D(1) receptor with K(i) values of 50 and 6.3nM, while both compounds act as D(2) receptor antagonists (K(i)=305 and 145nM, respectively) and 5-HT(1A) receptor full agonists (K(i)=149 and 908nM, respectively). These two THPBs compounds exerted antipsychotic actions in animal models. Further electrophysiological studies employing single-unit recording in intact animals demonstrated that 18k-excited dopaminergic (DA) neurons are associated with its 5-HT(1A) receptor agonistic activity. These results suggest that these two compounds targeted to multiple neurotransmitter receptors may present novel lead drugs with new pharmacological profiles for the treatment of schizophrenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. 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.

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

    Science.gov (United States)

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

    2012-04-01

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

  15. Potential antipsychotic agents. 7. Synthesis and antidopaminergic properties of the atypical highly potent (S)-5-bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide and related compounds. A comparative study.

    Science.gov (United States)

    Högberg, T; de Paulis, T; Johansson, L; Kumar, Y; Hall, H; Ogren, S O

    1990-08-01

    (S)-5-Bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (6) and some related compounds, i.e. the R isomer 7, the 3-hydroxy analogue 8, the desbromo derivative 9, the monomethoxy compound 10, and the 2,4-dimethoxy analogue 11, have been synthesized from the corresponding benzoic acids. The benzamides, lacking o-hydroxy groups, were evaluated for their affinity for the [3H]spiperone binding site and for their inhibition of apomorphine-induced behavioral responses in relation to the effect of the corresponding salicylamides. Besides the 2-hydroxy-3-methoxybenzamide 12 and the related 1,4-benzodioxane (13) and 2,3-dihydrobenzofuran (14), carboxamides were investigated in order to evaluate the stereoelectronic requirements on the 2-methoxy group for the receptor interaction. The study supports the view that the o-methoxy group may adopt coplanar, as well as perpendicular orientations, and maintain the intramolecular hydrogen bonding required in the bioactive conformation. The benzamide 6 was found to be equipotent with the analogous highly active salicylamide 3 (FLB 463) both in vitro and in vivo. In addition, 6 displayed a preferential inhibition of the hyperactivity component of the behavioral syndrome, which is regarded to indicate a low tendency to induce extrapyramidal side effects in man at antipsychotically effective doses. The benzamide class of compounds (6-10) were found to be somewhat more sensitive to the structural modifications than the salicylamide class, i.e. the o-hydroxy-substituted benzamides (2-5). The potent and selective benzamide 6 (FLB 457) is highly suitable for investigations of dopamine D-2 mediated responses and, in radiolabeled form, for receptor binding studies in vitro and in vivo.

  16. Risk of pneumonia in elderly nursing home residents using typical versus atypical antipsychotics.

    Science.gov (United States)

    Aparasu, Rajender R; Chatterjee, Satabdi; Chen, Hua

    2013-04-01

    Antipsychotic medications are extensively used in nursing homes for management of behavioral and psychiatric disorders in the elderly. Prior research suggests that pneumonia is one of the common causes of anti psychotic-related mortality in this population. None of the studies compared typical and atypical antipsychotics with respect to pneumonia. To examine the risk of pneumonia with use of typical versus atypical antipsychotics in dual eligible elderly nursing home residents. The study involved a retrospective cohort design matched on propensity score using Medicare and Medicaid Analytical eXtract data from 4 US states. The study population included all elderly dual eligible (Medicaid and Medicare) nursing home residents (aged ≥65 years) who initiated antipsychotics any time between July 1, 2001, and December 31, 2003. The risk of pneumonia during the 6-month follow-up period was modeled using a Cox proportional model and extended Cox hazard model stratified on matched pairs based on propensity score, using atypical agents as the reference category. Analysis of Medicaid-Medicare data revealed that there were 49,904 new antipsychotic (46,293 atypical and 3611 typical) users in the unmatched cohort and 7218 (3609 atypical and 3609 typical) users in the matched cohort. The unadjusted rate of pneumonia was 8.17% (4.61 events per person year) for atypical users and 5.21% (5.21 events per person year) for typical users. HR 1.17, 95% CI 0.83-1.66; and 50-180 days: HR 1.36, 95% CI 0.87-2.14) suggest that there was no significant difference in the risk of pneumonia among typical and atypical users. The study found no differential risk of pneumonia between typical versus atypical antipsychotic use in dual eligible nursing home residents. Given the differential risk of mortality with typical and atypical antipsychotic use in nursing homes, more research is needed to evaluate other contributory factors of mortality with respect to these 2 antipsychotic classes.

  17. Temporal and Spatial Transcriptional Fingerprints by Antipsychotic or Propsychotic Drugs in Mouse Brain

    Science.gov (United States)

    Sakuma, Kensuke; Komatsu, Hidetoshi; Maruyama, Minoru; Imaichi, Sachiko; Habata, Yugo; Mori, Masaaki

    2015-01-01

    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. PMID:25693194

  18. 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

  19. Off-label utilization of antipsychotics

    African Journals Online (AJOL)

    Adele

    seldom received a combination of an atypical and a conventional antipsychotic, whereas a lesser number of patients with off- label indications received atypical antipsychotics less often than those of the two comparison groups (p<0.05). Stepwise logistic regression revealed that patients with a psychotic disorder were more ...

  20. Constrictive Pericarditis Associated with Atypical Antipsychotics

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Antipsychotic Use and Risk of Hospitalization or Death Due to Pneumonia in Persons With and Those Without Alzheimer Disease.

    Science.gov (United States)

    Tolppanen, Anna-Maija; Koponen, Marjaana; Tanskanen, Antti; Lavikainen, Piia; Sund, Reijo; Tiihonen, Jari; Hartikainen, Sirpa; Taipale, Heidi

    2016-12-01

    The use of antipsychotic agents has been associated with increased pneumonia risk, but although people with dementia are particularly susceptible to pneumonia, only one small study has assessed the risk of pneumonia in relation to the use of antipsychotic agents among people with Alzheimer disease (AD). We investigated whether the incident use of antipsychotic agents, or specific antipsychotic agents, are related to a higher risk of hospitalization or death due to pneumonia in the Medication and Alzheimer Disease (MEDALZ) cohort. The cohort includes all individuals with AD who received a clinically verified AD diagnosis in Finland in 2005 to 2011 (N = 60,584; incident pneumonia, n = 12,225). A matched comparison cohort without AD (N = 60,584; incident pneumonia, n = 6,195) was used to compare the magnitude of risk. Results were adjusted for a propensity score derived from comorbidities, concomitant medications, and sociodemographic characteristics. Sensitivity analyses with case-crossover design were conducted. The use of antipsychotic agents was associated with a higher risk of pneumonia (adjusted hazard ratio [HR], 2.01; 95% CI, 1.90-2.13) in the AD cohort and a somewhat higher risk in the non-AD cohort (adjusted HR, 3.43; 95% CI, 2.99-3.93). Similar results were observed with case-crossover analyses (OR, 2.02; 95% CI, 1.75-2.34 in the AD cohort and OR, 2.59; 95% CI, 1.77-3.79 in the non-AD cohort). The three most commonly used antipsychotic agents (quetiapine, risperidone, haloperidol) had similar associations with pneumonia risk. Regardless of applied study design, treatment duration, or the choice of drug, the use of antipsychotic agents was associated with a higher risk of pneumonia. With observational data, we cannot fully rule out a shared causality between pneumonia and the use of antipsychotic agents, but the risk to benefit balance should be considered when antipsychotic agents are prescribed. Copyright © 2016 American College of Chest

  3. 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

  4. Antipsychotic Prescriptions Among Adults With Major Depressive Disorder in Office-Based Outpatient Settings: National Trends From 2006 to 2015.

    Science.gov (United States)

    Rhee, Taeho Greg; Mohamed, Somaia; Rosenheck, Robert A

    2018-02-13

    A recent moderately long-term study found an antipsychotic to be more effective than an antidepressant as the next-step treatment of unresponsive major depressive disorder (MDD). It is thus timely to examine recent trends in the pharmacoepidemiology of antipsychotic treatment of MDD. Data from the 2006-2015 National Ambulatory Medical Care Survey, nationally representative samples of office-based outpatient visits in adults with MDD (ICD-9-CM codes 296.20-296.26 and 296.30-296.36) (n = 4,044 unweighted), were used to estimate rates of antipsychotic prescribing over these 10 years. Multivariable logistic regression analysis identified demographic and clinical factors independently associated with antipsychotic use in MDD. Antipsychotic prescribing for MDD increased from 18.5% in 2006-2007 to 24.9% in 2008-2009 and then declined to 18.9% in 2014-2015. Visits with adults 75 years or older showed the greatest decline from 27.0% in 2006-2007 to 10.7% in 2014-2015 (OR for overall trend = 0.73; 95% CI, 0.56-0.95). The most commonly prescribed antipsychotic agents were aripiprazole, olanzapine, quetiapine, and risperidone. Antipsychotic prescription was associated with being black or Hispanic, having Medicare among adults under 65 years or Medicaid as a primary source of payment, and receiving mental health counseling, 3 or more concomitant medications, and diagnosis of cannabis use disorder (P < .01). Antipsychotics, prescribed for about one-fifth of adults with MDD, increased and then declined from 2006 to 2015, reflecting, first, FDA approval and then concern about adverse effects in the elderly. Future research should track evolving trends following the publication of evidence of greater long-term effectiveness of antipsychotic than antidepressant next-step therapy in adults with MDD. © Copyright 2018 Physicians Postgraduate Press, Inc.

  5. Aripiprazole versus other atypical antipsychotics for schizophrenia.

    Science.gov (United States)

    Khanna, Priya; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; El-Sayeh, Hany George; Leucht, Stefan

    2013-02-28

    In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study. We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended

  6. Antipsychotic Drugs on Maternal Behavior in Rats

    OpenAIRE

    Li, Ming

    2015-01-01

    Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole and amisulpride, all disrupt active maternal responses (e.g. pup retrieval, pup licking and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior i...

  7. ATYPICAL ANTIPSYCHOTICS USE IN CHILDREN AND ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    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.

  8. Antipsychotic exposure prior to acute myocardial infarction in patients with serious mental illness.

    Science.gov (United States)

    Wu, S-I; Kao, K-L; Chen, S-C; Juang, J J M; Lin, C-J; Fang, C-K; Wu, C-S; Dewey, M; Prince, M J; Stewart, R

    2015-03-01

    To investigate the association between acute myocardial infarction (AMI) and recent exposure to antipsychotic agents in people with serious mental illness (SMI), and modifying influences. A case-crossover design was applied using the Taiwan National Health Insurance Research Database (NHIRD) to compare the exposure frequency of antipsychotic agents within individuals of schizophrenia or bipolar disorder between 60-day case and control periods prior to their first AMI episode during 1996-2007. A sample of 834 patients with incident AMI was analysed. AMI was significantly associated with more recent antipsychotic exposure in schizophrenia after adjustment (OR 1.87, 95% confidence interval 1.15-3.03) bipolar disorder (OR 1.06, 0.51-2.21). This association in schizophrenia was significantly stronger in men and in patients without previous diagnoses of cardiovascular risk factors. These findings are consistent with a short-term risk effect of antipsychotic exposure on risk of AMI and identify potentially vulnerable groups. Further research is required to clarify underlying biological mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Role of atypical antipsychotics in the treatment of generalized anxiety disorder.

    Science.gov (United States)

    Hershenberg, Rachel; Gros, Daniel F; Brawman-Mintzer, Olga

    2014-06-01

    Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60-70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed.

  10. 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

  11. 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.

  12. 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

  13. Effects of α7 nicotinic acetylcholine receptor agonists on antipsychotic efficacy in a preclinical mouse model of psychosis.

    Science.gov (United States)

    Kohlhaas, Kathy L; Bitner, Robert S; Gopalakrishnan, Murali; Rueter, Lynne E

    2012-04-01

    Antipsychotics normalize responses in the DBA/2 mouse model of prepulse inhibition (PPI), a preclinical model of sensorimotor gating deficits. The α7 nicotinic acetylcholine receptor (nAChR) as a molecular target is considered an attractive approach for improvement of cognitive deficits in schizophrenia (CDS). Assessment of clinical efficacy of novel agents in CDS involves treating patients already on antipsychotic medications. We evaluated the effects of the combination of α7 nAChR agonists ABT-107 (0.1-10.0 mg/kg i.p.), A-582941 (0.04-4.0 mg/kg i.p.), and PNU282987 (1.0-10.0 mg/kg i.p.) with risperidone (0.1-1.0 mg/kg i.p.) or haloperidol (0.3-3.0 mg/kg i.p.), representative atypical and typical antipsychotic agents in the DBA/2 mouse PPI model. The same α7 agonists were given alone or in combination with a dose of antipsychotic medication that induces a minimal level of catalepsy in rats, an assay with predictive validity for the induction of extrapyramidal symptoms. The α7 nAChR agonists ABT-107, A-582941, and PNU282987 had no effect in DBA/2 mouse PPI when given alone yet increased the effects of haloperidol and risperidone. The α7 nAChR agonists did not cause catalepsy in rats, nor did they enhance antipsychotic-induced catalepsy. When given in combination with either a typical or atypical antipsychotic, α7 nAChR agonists did not impair efficacy in the DBA/2 J mouse PPI model. The efficacy but not the motoric side effects of antipsychotics was enhanced, suggesting that adjunctive therapy of α7 nAChR agonists not only could be useful for the treatment of cognitive deficits associated with schizophrenia but also could enhance the efficacy against positive symptoms.

  14. Do we need another atypical antipsychotic?

    Science.gov (United States)

    Kasper, Siegfried

    2008-08-01

    Atypical antipsychotics were a great advance in the treatment of schizophrenia. But, there is still no atypical antipsychotic with an exceptional efficacy and safety profile for all patients. Clinicians are required to draw on their experiential knowledge to examine suitable options for individual patients. Following its suspension in 1998, the safety and efficacy of sertindole have been investigated in several post-marketing studies based in clinical settings. These have provided the safety data to support the reintroduction of sertindole, as well as specific examples demonstrating that certain patients, in particular, may benefit from a switch from other atypical antipsychotics to sertindole. Sertindole's individual and mostly favourable profile of treatment-emergent effects and safety allows for flexibility in treating patients. The propensity of sertindole to cause anticholinergic effects, which can be particularly troublesome, is small and, more recently, there have been suggestions that sertindole may have beneficial effects on cognition.

  15. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

    Directory of Open Access Journals (Sweden)

    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  16. Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    El-Sayeh, Hany G; Rathbone, John; Soares-Weiser, Karla; Bergman, Hanna

    2018-01-18

    Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. 1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years). We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia. We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people

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

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

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

  18. 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.

  19. The Place of Antipsychotics in the Therapy of Anxiety Disorders and Obsessive-Compulsive Disorders.

    Science.gov (United States)

    Pignon, Baptiste; Tezenas du Montcel, Chloé; Carton, Louise; Pelissolo, Antoine

    2017-11-07

    The purpose of this review was to assess and present the findings up to this date on the efficacy of antipsychotics in the treatment of generalized anxiety disorders (GAD), social anxiety disorders (SAD), panic disorders (PD), and obsessive-compulsive disorders (OCD), mostly based on published randomized controlled trials (RCTs) or on open-label studies when RCT were lacking. Quetiapine could be recommended in patients with GAD. The efficacy of aripiprazole in two open-label studies on patients with antidepressant-refractory GAD should be assessed in RCTs. Despite preliminary positive results in open studies, there are currently no strong evidence for the effectiveness of antipsychotics in refractory SAD and in refractory PD. Conversely, risperidone and aripiprazole can be used for the treatment of refractory OCD as augmentation agents to antidepressants. Contrary to SAD and PD, this review found evidence for the use of second-generation antipsychotics in GAD and OCD. Otherwise, first-generation antipsychotics cannot be recommended in anxiety disorders and OCD.

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

    Directory of Open Access Journals (Sweden)

    Ronny T Wirasto

    2016-12-01

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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Mahantesh Namdev Jadhav

    2013-01-01

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

  3. Off-label utilization of antipsychotics

    African Journals Online (AJOL)

    Adele

    As part of a pharmacovigilance/pharmacoepidemiology program, all drugs given on 5 reference days (1999 – 2001) in the 98- bed psychiatric ... Key words: Antipsychotic drugs; Off-label use; Prescription habits; Psychotic disorders; Affective disorders ..... Laux G, Baier D. Quality-monitoring of psychotropic drug therapy in.

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

    African Journals Online (AJOL)

    Purpose: To evaluate the antipsychotic drugs most commonly prescribed for schizophrenia patients in Peshawar, Pakistan and to analyze the treatment costs associated with these drugs. Methods: One hundred patients diagnosed with schizophrenia were recruited from outpatient psychiatry departments in Peshawar, ...

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

    African Journals Online (AJOL)

    Purpose: To evaluate the antipsychotic drugs most commonly prescribed for schizophrenia patients in. Peshawar, Pakistan and to analyze the treatment costs associated with these drugs. Methods: One hundred patients diagnosed with schizophrenia were recruited from outpatient psychiatry departments in Peshawar, ...

  6. Antipsychotic medication non-adherence among schizophrenia ...

    African Journals Online (AJOL)

    2018-03-05

    Mar 5, 2018 ... factors associated with antipsychotic medication non-adherence among schizophrenia patients .... treatment. Results. Socio-demographic characteristics of schizophrenia patients. Out of the total 423 recruited patients, 412 filled in the questionnaire ... involving chewing parts of the fresh green leaves.

  7. Fall and Fracture Risk in Nursing Home Residents With Moderate-to-Severe Behavioral Symptoms of Alzheimer's Disease and Related Dementias Initiating Antidepressants or Antipsychotics.

    Science.gov (United States)

    Wei, Yu-Jung; Simoni-Wastila, Linda; Lucas, Judith A; Brandt, Nicole

    2017-05-01

    Both antidepressants and antipsychotics are used in older adults with behavioral symptoms of Alzheimer's disease and related dementias. Despite the prevalent use of these agents, little is known about their comparative risks for falls and fractures. Using 2007-2009 Medicare claims data linked to Minimum Data Set 2.0, we identified new users of antidepressants and antipsychotics among nursing home residents with Alzheimer's disease and related dementias who had moderate-to-severe behavioral symptoms. Separate discrete-time survival models were used to estimate risks of falls, fractures, and a composite of both among antidepressant group versus antipsychotic group. Compared to antipsychotic users, antidepressant users experienced significantly higher risk for fractures (adjusted hazard ratio = 1.35, 95% confidence interval = 1.10-1.66). The overall risk of falls or fractures remained significant in the antidepressant versus antipsychotic group (adjusted hazard ratio = 1.16, 95% confidence interval = 1.02-1.32). Antidepressants are associated with higher fall and fracture risk compared to antipsychotics in the management of older adults with Alzheimer's disease and related dementias who experience moderate-to-severe behavioral symptoms. Clinicians need to assess the ongoing risks/benefits of antidepressants for these symptoms especially in light of the increasingly prevalent use of these agents. © The Author 2016. 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.

  8. Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders.

    Science.gov (United States)

    Dold, Markus; Samara, Myrto T; Li, Chunbo; Tardy, Magdolna; Leucht, Stefan

    2015-01-16

    Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first-generation ("conventional", "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first-generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high-quality systematic review appeared highly necessary. To compare the efficacy, acceptability, and tolerability of haloperidol with other first-generation antipsychotics in schizophrenia and schizophrenia-like psychosis. In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data. We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first-generation antipsychotic drug (with the exception of the low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse

  9. Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia.

    Science.gov (United States)

    Bergman, Hanna; Rathbone, John; Agarwal, Vivek; Soares-Weiser, Karla

    2018-02-06

    Since the 1950s antipsychotic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Various strategies have been examined to reduce a person's cumulative exposure to antipsychotics. These strategies include dose reduction, intermittent dosing strategies such as drug holidays, and antipsychotic cessation. To determine whether a reduction or cessation of antipsychotic drugs is associated with a reduction in TD for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific antipsychotics for similar groups of people could be a treatment for TD that was already established. We updated previous searches of Cochrane Schizophrenia's study-based Register of Trials including the registers of clinical trials (16 July 2015 and 26 April 2017). We searched references of all identified studies for further trial citations. We also contacted authors of trials for additional information. We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established antipsychotic-induced TD, and had been randomly allocated to (a) antipsychotic maintenance versus antipsychotic cessation (placebo or no intervention), (b) antipsychotic maintenance versus antipsychotic reduction (including intermittent strategies), (c) specific antipsychotics for the treatment of TD versus placebo or no intervention, and (d) specific antipsychotics versus other antipsychotics or versus any other drugs for the treatment of TD. We independently extracted data from these trials and estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who

  10. A systematic review of the antipsychotic properties of cannabidiol in humans.

    Science.gov (United States)

    Iseger, Tabitha A; Bossong, Matthijs G

    2015-03-01

    Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side effects. Therefore, there is an urgent need for novel therapeutic targets for the treatment of schizophrenia. A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system. Modulation of this system by the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia. Here we review studies that investigated the antipsychotic properties of CBD in human subjects. Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration. In addition, CBD may lower the risk for developing psychosis that is related to cannabis use. These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex. The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomised clinical trials will be needed before this novel therapy can be introduced into clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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

  12. Antipsychotic-induced somnolence in mothers with schizophrenia.

    Science.gov (United States)

    Seeman, Mary V

    2012-03-01

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

  13. CARDIOTOXICITY ANTIPSYCHOTICS: MORPHO-ELECTROCARDIOGRAPHIC ASSOCIATIONS

    Directory of Open Access Journals (Sweden)

    V. P. Volkov

    2015-12-01

    Full Text Available Aim. To study the morphological and functional heart disorders in patients with different duration of antipsychotic treatment. Material and methods. Medical documents of 78 deceased schizophrenic patients treated with antipsychotic drugs were studied. The patients were split into 4 groups depending on duration of neuroleptic treatment: group 1 — <10 years, group 2 — 11-20 years; group 3 — 21-30 years, group 4 — >30 years. ECG-disorders and left ventricular morphometric data were analyzed. Сorrelation analysis of myocardium morphological changes and electrophysiological disorders was performed. Results. The dependence of morphometric myocardium changes on the treatment duration was found: increase in stromal-parenchymal ratio (from 9.9±4.1% to 80.0±10.1% in groups 1 and 4, respectively, in specific volume of atrophied cardiomyocytes (from 8.0±3.8% to 45.1±12.6% in groups 1 and 4, respectively, in specific volume of degenerative cardiomyocytes (from 5.2±3.1% to 35.2±12.1% in groups 1 and 4, respectively. Increased incidence of extrasystole detection (from 2.2% to 11.2% in groups 1 and 2, respectively, as well as left anterior fascicular block (from 1.1% to 25.9% in groups 1 and 2, respectively and left ventricle hypertrophy (from 2.2% to 18.5% in groups 1 and 4, respectively were found. A strong positive correlation (r=0.88–0.99 was revealed between antipsychotic treatment duration and ECG disorders, as well as between morphological myocardium state and ECG disorders. Conclusion. Awareness about the neuroleptic-depended ECG changes is necessary for early diagnosis, secondary prevention and correction of existing heart disorders due to cardiotoxic side effects of antipsychotic drugs.

  14. CARDIOTOXICITY ANTIPSYCHOTICS: MORPHO-ELECTROCARDIOGRAPHIC ASSOCIATIONS

    Directory of Open Access Journals (Sweden)

    V. P. Volkov

    2012-01-01

    Full Text Available Aim. To study the morphological and functional heart disorders in patients with different duration of antipsychotic treatment. Material and methods. Medical documents of 78 deceased schizophrenic patients treated with antipsychotic drugs were studied. The patients were split into 4 groups depending on duration of neuroleptic treatment: group 1 — <10 years, group 2 — 11-20 years; group 3 — 21-30 years, group 4 — >30 years. ECG-disorders and left ventricular morphometric data were analyzed. Сorrelation analysis of myocardium morphological changes and electrophysiological disorders was performed. Results. The dependence of morphometric myocardium changes on the treatment duration was found: increase in stromal-parenchymal ratio (from 9.9±4.1% to 80.0±10.1% in groups 1 and 4, respectively, in specific volume of atrophied cardiomyocytes (from 8.0±3.8% to 45.1±12.6% in groups 1 and 4, respectively, in specific volume of degenerative cardiomyocytes (from 5.2±3.1% to 35.2±12.1% in groups 1 and 4, respectively. Increased incidence of extrasystole detection (from 2.2% to 11.2% in groups 1 and 2, respectively, as well as left anterior fascicular block (from 1.1% to 25.9% in groups 1 and 2, respectively and left ventricle hypertrophy (from 2.2% to 18.5% in groups 1 and 4, respectively were found. A strong positive correlation (r=0.88–0.99 was revealed between antipsychotic treatment duration and ECG disorders, as well as between morphological myocardium state and ECG disorders. Conclusion. Awareness about the neuroleptic-depended ECG changes is necessary for early diagnosis, secondary prevention and correction of existing heart disorders due to cardiotoxic side effects of antipsychotic drugs.

  15. 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

  16. 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...

  17. 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

  18. Risk of Hospitalization for Hypoglycemia in Older Patients with Diabetes Using Antipsychotic Drugs

    NARCIS (Netherlands)

    van Keulen, Kris; van der Linden, Paul D; Souverein, Patrick C; Heerdink, Eibert R; Egberts, Toine; Knol, Wilma

    2015-01-01

    OBJECTIVE: Antipsychotics may disrupt metabolic regulation in patients with diabetes mellitus. The risk of hypoglycemia in older users of antipsychotics with diabetes is largely unknown. Therefore, we investigated the association between the use of antipsychotic drugs and hypoglycemia requiring

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

    Directory of Open Access Journals (Sweden)

    Chandravadivelu Gopi

    2017-12-01

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

  20. [Prolactin, antipsychotics and breast cancer: is there a connection?].

    Science.gov (United States)

    Sabbe, T; Detraux, J; De Hert, M

    The use of antipsychotics can result in elevated prolactin levels or hyperprolactinemia. An increasing number of studies suggests that prolactin plays a role in mammary carcinogenesis, leading to concerns about a possible relationship between antipsychotics and breast cancer. To provide an overview of recent literature regarding the relationship between prolactin, antipsychotics and breast cancer and an association between schizophrenia and breast cancer. We used PubMed to search for English- or Dutch-language articles concerning breast cancer risk (factors), prolactin, antipsychotics and schizophrenia. Studies have not shown any causal link between antipsychotics and the development of breastcancer. Moreover, antipsychotic medication seems to have no influence on locally produced prolactin - which some experts believe plays a role in the tumor genesis - and certain antipsychotics actually provide protection against breast cancer. There are conflicting reports on the prevalence of breast cancer among patients with schizophrenia. Nevertheless, research has revealed that several well-known risk factors for breast cancer (such as an unhealthy lifestyle) are more prevalent in patients with schizophrenia. There is no conclusive evidence that antipsychotic medication that raises prolactin levels increases the risk of breast cancer. Nevertheless, clinicians should always be cautious about prescribing antipsychotics for breast cancer patients. In our view, clinicians should always treat breast cancer risk factors as efficiently as possible, particularly when attending to patients who have schizophrenia.

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

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

    not inducing weight gain in clinic (haloperidol), on food and water intake and body weight gain in rats. We included both female and male rats in this study. To reduce spontaneous high food intake in rats, and to be able to evaluate the treatment effect on a potential increase of food intake or metabolic......Several clinical reports have demonstrated that most antipsychotics of the new generation, but not the typical antipsychotic haloperidol, induce weight gain in schizophrenic patients. Since weight gain induces serious health complications in humans, it is crucial to test upcoming antipsychotic...... compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

  2. Aripiprazole versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

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

    2014-01-01

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

  3. Prolactin-Elevating Antipsychotics and the Risk of Endometrial Cancer.

    Science.gov (United States)

    Klil-Drori, Adi J; Yin, Hui; Abenhaim, Haim A; du Fort, Guillaume Galbaud; Azoulay, Laurent

    2017-06-01

    The use of antipsychotics may increase the risk of endometrial cancer through elevation of prolactin levels. We investigated the association between antipsychotics that are known to cause prolactin elevation and the risk of endometrial cancer. In data from the United Kingdom Clinical Practice Research Datalink, all women who were newly treated with antipsychotics from 1990-2013 were identified and followed until 2014. Within this cohort of antipsychotic users, a nested case-control analysis was conducted. Main exposure was nonsporadic use of prolactin-elevating antipsychotics, and the active comparator was prolactin-sparing antipsychotics. Cases were women newly diagnosed with endometrial cancer (ICD-10) matched with up to 20 controls on age, calendar year of cohort entry, linkability to the Hospital Episode Statistics repository, and duration of follow-up. Conditional logistic regression models were used to determine the association of prolactin-elevating antipsychotics and endometrial cancer compared with prolactin-sparing antipsychotics. All analyses were adjusted for relevant potential confounders, including smoking, obesity, and diabetes mellitus. The cohort included 65,930 women. During 366,112 person-years of follow-up, there were 139 cases of endometrial cancer (incidence rate: 38/100,000 person-years), which were matched to 1,603 controls. Compared with the use of prolactin-sparing antipsychotics, the use of prolactin-elevating antipsychotics was not associated with an increased risk of endometrial cancer (adjusted odds ratio [aOR] = 1.00; 95% CI, 0.68-1.48). These findings remained similar with different durations of use (≤ 1 year, aOR = 1.07; 95% CI, 0.64-1.78, and > 1 year, aOR = 0.95; 95% CI, 0.58-1.54) and were robust to various sensitivity analyses. Prolactin-elevating antipsychotics were not associated with an increased risk of endometrial cancer. © Copyright 2017 Physicians Postgraduate Press, Inc.

  4. 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

  5. Patient perspectives on antipsychotic treatments and their association with clinical outcomes

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    2010-09-01

    Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

  6. Adherence of mentally stable patients to antipsychotic medications ...

    African Journals Online (AJOL)

    The results of this study indicated that participants shared same viewpoints related to aspects of adherence to antipsychotic treatment; the mentally stable patients have knowledge related to the causes of mental illness; poor adherence to antipsychotic treatment results from the health seeking behaviour of the patients.

  7. Antipsychotic use in elderly patients and the risk of pneumonia.

    Science.gov (United States)

    Gambassi, Giovanni; Sultana, Janet; Trifirò, Gianluca

    2015-01-01

    Antipsychotics are frequently and increasingly prescribed off-label for the treatment of behavioral and psychological symptoms associated with dementia, despite their modest efficacy. Instead, the safety profile of antipsychotics has been questioned repeatedly in recent years with various concerns, including death. Meta-analyses of randomized controlled trials found that one of the major causes of death associated with atypical antipsychotics use was pneumonia. Only few observational studies, however, have investigated the risk of pneumonia in elderly patients, especially among those receiving conventional antipsychotics. The aim of this editorial is to synthesize the current evidence from observational studies regarding the risk of pneumonia in elderly patients receiving either conventional or atypical antipsychotics. The studies conducted so far document that the risk of pneumonia is two- to threefold increased in a dose-dependent fashion with both classes compared to nonuse, with a possibly higher risk attributable to atypical antipsychotics. The risk seems to peak at the beginning of treatment (e.g., 7 - 30 days), and dissipates over time for both conventional and atypical antipsychotics. The risk-benefit ratio suggests that there will be 1 excess hospitalization for pneumonia for every 2 - 5 patients receiving any clinical improvement in symptoms. Considering the modest improvement in terms of efficacy, the risks associated with antipsychotics in elderly patients may outweigh their benefit.

  8. 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:

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

    International Nuclear Information System (INIS)

    Wu Jinchang; Jiang Yimin

    1989-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    Background: High dose antipsychotic prescribing is common in psychiatric care, despite a lack of its benefit from research evidence. While several studies have explored the prevalence and factors associated with high dose antipsychotic prescribing, no such report has emanated from a developing country like Nigeria.

  12. Sertindole versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

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

    2014-01-01

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

  13. [ADD psychosis: treatment with antipsychotics and methylphenidate?].

    Science.gov (United States)

    Blom, J D; Kooij, J J S

    2012-01-01

    Two patients with a psychotic disorder who also met the diagnostic criteria for attention deficit hyperactivity disorder ADHD were treated with antipsychotics and methylphenidate. The first patient remained stable for many years with this combination treatment, whereas the second became psychotic several months after he had increased the dose of methylphenidate and had started to use cocaine. In the light of these two case studies, we have reviewed the literature on ADD psychosis, and we formulate recommendations regarding the specialised treatment needed for this uncommon disorder.

  14. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE...... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...... with the antipsychotic compound amisulpride. Controls were followed up without treatment. MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as measured by functional magnetic resonance imaging before and after antipsychotic treatment. RESULTS At baseline, patients, as compared with controls...

  15. Antipsychotic use in nursing homes varies by psychiatric consultant.

    Science.gov (United States)

    Tjia, Jennifer; Field, Terry; Lemay, Celeste; Mazor, Kathleen; Pandolfi, Michelle; Spenard, Ann; Ho, Shih-Yieh; Kanaan, Abir; Donovan, Jennifer; Gurwitz, Jerry H; Briesacher, Becky

    2014-03-01

    The relationship between psychiatric consultation and antipsychotic prescribing in nursing homes (NH) is unknown. To identify the association between psychiatric consultant groups and NH-level antipsychotic prescribing after adjustment for resident case-mix and facility characteristics. Nested cross-sectional study of 60 NHs in a cluster randomized trial. We linked facility leadership surveys to October 2009-September 2010 Minimum Data Set, Nursing Home Compare, the US Census, and pharmacy dispensing data. The main exposure is the psychiatric consultant group and the main outcome is NH-level prevalence of atypical antipsychotic use. We calculated annual means and interquartile ranges of NH-level antipsychotic use for each consultant group and arrayed consultant groups from lowest to highest prevalence. Generalized linear models were used to predict antipsychotic prescribing adjusting for resident case-mix and facility characteristics. Observed versus predicted antipsychotic prescribing levels were compared for each consultant group. Seven psychiatric consultant groups served a range of 3-27 study facilities. Overall mean facility-level antipsychotic prescribing was 19.2%. Mean prevalence of antipsychotic prescribing ranged from 12.2% (SD, 5.8) in the lowest consultant group to 26.4% (SD, 3.6) in the highest group. All facilities served by the highest-ranked consultant group had observed antipsychotic levels exceeding the overall study mean with half exceeding predictions for on-label indications, whereas most facilities served by the lowest-ranked consultant group had observed levels below the overall study and predicted means. Preliminary evidence suggests that psychiatric consultant groups affect NH antipsychotic prescribing independent of resident case-mix and facility characteristics.

  16. 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 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 drugs during hospitalization was not associated with in-hospital or follow-up mortality. Short

  17. Amisulpride versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

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

    2014-01-01

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

  18. Antipsychotic treatment: experiences of fully recovered service users.

    Science.gov (United States)

    Bjornestad, Jone; Davidson, Larry; Joa, Inge; Larsen, Tor Ketil; Hegelstad, Wenche Ten Velden; Langeveld, Johannes; Veseth, Marius; Melle, Ingrid; Johannessen, Jan Olav; Bronnick, Kolbjorn

    2017-06-01

    There is lack of long-term controlled studies evaluating treatment effects of antipsychotic medication. A complete investigation should include the service user perspective. To investigate experiences of clinically recovered service users of antipsychotic medications during and after a first episode of psychosis. We used a thematic analytic approach within an interpretative-phenomenological framework. 20 clinically recovered service users were interviewed. Themes: (1) Antipsychotic drugs reduce mental chaos during the acute phase, (2) Non-stigmatizing environments were perceived to increase chances of successful use, (3) Antipsychotic drugs beyond the acute phase - considered to compromise the contribution of individual effort in recovery, (4) Prolonged use - perceived to reduce likelihood of functional recovery, (5) Antipsychotic medication was considered as a supplement to trustful relationships. Acute phase antipsychotic treatment was mostly perceived as advantageous by this sample, who was in clinical recovery. However, costs were often seen as outweighing benefits beyond the acute stage. Findings clearly emphasize the need for a collaborative approach to be integrated across all phases of care. This study underscores the need to investigate sub-group differences with regard to long-term antipsychotic treatment.

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

    Science.gov (United States)

    Haefliger, T; Bonsack, C

    2006-01-01

    of potential negative consequences (ie increased risk of osteoporosis or neoplasia, worsening of psychopathology) (34). When hyperprolactinemia is symptomatic, lowering of the dose of the antipsychotic, or switching to a prolactin-sparing agent (olanzapine, quetiapine, aripiprazole and clozapine) is recommended. Before this, women with amenorrhea secondary to antipsychotic-induced hyperprolactinemia should be advised that menses may resume. Especially after long-standing amenorrhea they may assume being menopaused, hence may believe birth control measures are no longer required. The prevalence of antipsychotic-induced sexual and reproductive function side-effects is high. Clinicians should be aware of them, because they are often badly tolerated, are associated with a low satisfaction and may therefore result in low adherence with treatment. This implies for the clinician to overtly discuss with the patient of his sexuality and the potential negative impact of antipsychotic treatment on it. The recognition of these problems allows the searching together for a solution. The described cases indicate that solving the problem is often possible, provided that individual preferences and subjective impact are taken in account. Antipsychotic treatment is often prescribed for very long periods. A better knowledge of - and attention to - the associated side effects, particularly on the sexual and reproductive functions, is necessary in order to reduce some potentially negative long-term effects and to improve the adherence to treatment of our patients.

  20. Geographic Distribution of Antipsychotic Use in Medicare Part D Patients

    Directory of Open Access Journals (Sweden)

    Angela Anthony

    2017-02-01

    Full Text Available Purpose: To determine if there is a geographic variation in antipsychotic prescribing in Medicare recipients in 10 US divisions. Methods: Data was collected in the Microsoft Excel format from the Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File for 2013 CMS data. Antipsychotics were sorted and downloaded into separate excel formats. The states were separated into the 10 geographic according to the US Census Bureau to identify prescribing trends. The primary endpoint was to determine the difference in the rates of CMS Medicare Part D utilizers who had antipsychotic prescriptions in each of the 10 geographic divisions. 
The rate of antipsychotic prescribing was calculated by determining the number of prescription claims for each antipsychotic for the division and dividing by the number of people utilizing Medicare Part D in each division. Data was converted to SPSS (version19, Armonk, NY for further analysis. ANOVA was used to compare the differences. Results: Approximately 35 million claims were included in the data set. Antipsychotics comprised 4.75% of the total spending on medications for Medicare Part D. New England was found to have the highest rate of claims at 0.83. No statistically significant differences in the rate of antipsychotic prescribing across geographic regions was observed; however, a statistically significant difference was observed for total claims (P<0.001 and total antipsychotic costs (P<0.017 across regions. Conclusion: Additional studies need to be conducted to determine if there is a difference in antipsychotic prescribing in the United States. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties

  1. Multiple Antipsychotic Medication Use in Autism Spectrum Disorder.

    Science.gov (United States)

    Wink, Logan K; Pedapati, Ernest V; Horn, Paul S; McDougle, Christopher J; Erickson, Craig A

    2017-02-01

    The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well

  2. Antipsychotic-associated psoriatic rash - a case report

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

    Baandrup, Lone; Gasse, Christiane; Jensen, Vibeke

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Baandrup, Lone; Gasse, Christiane; Jensen, Vibeke

    2010-01-01

    -matched controls. Current drug use was defined as at least 1 prescription filled within 90 days before the date of death or the index date. The data were analyzed by conditional logistic regression. RESULTS: Risk of natural death did not increase with the number of concurrently used antipsychotic agents compared......) was associated with increased risk of natural death in patients with schizophrenia treated with antipsychotics (OR = 1.78 [95% CI, 1.25-2.52]). CONCLUSIONS: Antipsychotic polypharmacy did not contribute to the excess mortality from natural causes in middle-aged patients with schizophrenia. The detected increased...... risk of death associated with benzodiazepines with long elimination half-lives calls for further clarification....

  5. Reduction in inpatient resource utilization and costs associated with long-acting injectable antipsychotics across different age groups of Medicaid-insured schizophrenia patients.

    Science.gov (United States)

    Kamat, Siddhesh A; Offord, Steve; Docherty, John; Lin, Jay; Eramo, Anna; Baker, Ross A; Gutierrez, Benjamin; Karson, Craig

    2015-01-01

    Evaluate utilization of inpatient healthcare resources and associated costs after 12 months of treatment using long-acting injectable (LAI) antipsychotic medications among a large sample of Medicaid-insured patients categorized by different age groups. Adult patients with schizophrenia were identified from the Thomson Reuters MarketScan Research database (1/1/2006-12/31/2010) before initiation of treatment using LAI antipsychotic agents. Utilization of inpatient healthcare resources and associated direct medical costs were compared for 12-month baseline and 12-month follow-up periods. Among 3,094 Medicaid-insured patients with schizophrenia initiating treatment with LAIs, the mean number of all-cause hospitalizations and hospitalization days were reduced by 24% and 31% (pultimate goal of antipsychotic treatment, results from this large Medicaid patient population establish the value of LAIs for the management of schizophrenia.

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

    Science.gov (United States)

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

    2008-08-01

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

  7. Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia.

    Science.gov (United States)

    de Bartolomeis, Andrea; Sarappa, Chiara; Magara, Salvatore; Iasevoli, Felice

    2012-05-05

    Antipsychotics are the mainstay of schizophrenia treatment. However, approximately one third of schizophrenic patients do not respond or respond poorly to antipsychotics. Therefore, there is a need for new approaches that can improve schizophrenia treatment significantly. Promising strategies arise from the modulation of glutamatergic system, according to its proposed involvement in schizophrenia pathogenesis. In this review, we critically updated preclinical and clinical data on the modulation of glutamate N-methyl-D-aspartate (NMDA) receptor activity by NMDA-Rs co-agonists, glycine transporters inhibitors, AMPAkines, mGluR5 agonists, NMDA-Rs partial agonists. We focused on: 1) preclinical results in animal models mimicking the pathophysiology of psychosis, mainly believed to be responsible of negative and cognitive symptoms, and predicting antipsychotic-like activity of these compounds; and 2) clinical efficacy in open-label and double-blind trials. Albeit promising preclinical findings for virtually all compounds, clinical efficacy has not been confirmed for D-cycloserine. Contrasting evidence has been reported for glycine and D-serine, that may however have a role as add-on agents. More promising results in humans have been found for glycine transporter inhibitors. AMPAkines appear to be beneficial as pro-cognitive agents, while positive allosteric modulators of mGluR5 have not been tested in humans. Memantine has been proposed in early stages of schizophrenia, as it may counteract the effects of glutamate excitotoxicity correlated to high glutamate levels, slowing the progression of negative symptoms associated to more advanced stages of the illness. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Temperature behaviour studies on antipsychotic drug Olanzapine

    Science.gov (United States)

    Dicle Erdamar, Işık Yeşim

    2017-12-01

    The antipsychotic drug Olanzapine in powder form was 60Co gamma irradiated to investigate in various temperature value. The Electron Paramagnetic Resonance (EPR) spectrum of the irradiated Olanzapine, characterized by g = 2.0030, exhibits an intensity distribution 1:2:1. The room temperature EPR spectra of gamma irradiated Olanzapine was recorded in DMSO solution at frozen state. Temperature behavior of Olanzapine discussed by means of similarities and differences of EPR parameters. Kinetic decay features of radicals induced by gamma irradiation of Olanzapine were also studied. EPR experiments indicated that Olanzapine contained stable free radical species after irradiation and the intensity of the signal is increasing with the absorbed doses suggesting increasing radical concentration in the system.

  9. 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.

  10. New atypical antipsychotics for schizophrenia: iloperidone

    Directory of Open Access Journals (Sweden)

    Silvio Caccia

    2010-02-01

    Full Text Available Silvio Caccia,1 Luca Pasina,2 Alessandro Nobili21Laboratory of Drug Metabolism, “Mario Negri” Institute for Pharmacological Research, Milan, Italy; 2Laboratory of Quality, Assessment of Geriatric Therapies and Services, “Mario Negri” Institute for Pharmacological Research, Milan, ItalyAbstract: The optimal treatment of schizophrenia poses a challenge to develop more effective treatments and safer drugs, to overcome poor compliance, discontinuation and frequent switching with available antipsychotics. Iloperidone is a new dopamine type 2/serotonin type 2A (D2/5-HT2A antagonist structurally related to risperidone, expected to give better efficacy with less extrapyramidal symptoms than D2 receptor antagonist antipsychotics. In double-blind phase III trials iloperidone reduced the symptoms of schizophrenia at oral doses from 12 to 24 mg. It was more effective than placebo in reducing positive and negative syndrome total score and Brief Psychiatric Rating scale scores; it was as effective as haloperidol and risperidone in post-hoc analysis. Its long-term efficacy was equivalent to that of haloperidol. The most common adverse events were dizziness, dry mouth, dyspepsia and somnolence, with few extrapyramidal symptoms and metabolic changes in short- and long-term studies in adults. Akathisia was rare, but prolongation of the corrected QT (QTc interval was comparable to haloperidol and ziprasidone, which is of particular concern. Further comparative studies are needed to clarify the benefit/risk profile of iloperidone and its role in the treatment of schizophrenia.Keywords: iloperidone, pharmacology, pharmacokinetics, efficacy, safety

  11. The personal, societal, and economic burden of schizophrenia in the People's Republic of China: implications for antipsychotic therapy

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2013-08-01

    antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People's Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment.Conclusion: Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People's Republic of China and globally. When treated effectively, patients tend to persist longer with antipsychotic treatment, have fewer costly relapses, and have improved functioning. Further research examining the long-term effects of reducing barriers to effective treatments on the societal burden of schizophrenia in the People's Republic of China is needed.Keywords: People's Republic of China, schizophrenia, relapse, review, health care costs, antipsychotic agents

  12. The antipsychotic story: changes in prescriptions and overdose without better safety

    Science.gov (United States)

    Buckley, Nicholas A.; Isbister, Geoffrey K.

    2016-01-01

    Aims Morbidity and mortality from drug overdose has decreased over three decades. This is credited to safer drugs and therefore better outcomes in overdose. We aimed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26‐year period. Methods All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were reviewed. Data were collected prospectively on demographics, ingestion information, clinical effects, complications and treatment. Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990–2011 and linked to overdose admissions by postcode. Results There were 3180 antipsychotic overdoses: 1235 first generation antipsychotics, 1695 ‘atypical’ second generation antipsychotics and 250 lithium overdoses. Over 26 years, antipsychotic overdoses increased 1.8‐fold, with first generation antipsychotics decreasing to one‐fifth of their peak (≈80/year to 16) and second generation antipsychotics increasing to double this (≈160/year), olanzapine and quetiapine accounting for 78%. All antipsychotic overdoses had a median length of stay of 18.6 h, 15.7% admitted to intensive care unit, 10.4% ventilated and 0.13% died in hospital, which was the same for first generation compared to second generation antipsychotics. There was a 2.3‐fold increase in antipsychotic prescriptions over the same period; first generation antipsychotics declined whereas there was a dramatic rise in second generation antipsychotics, mainly olanzapine, quetiapine and risperidone (79%). Conclusion Over 26 years there was an increase in antipsychotic prescribing associated with an increase in antipsychotic overdoses. Although the type of antipsychotics changed, the morbidity and mortality remained the same, so that antipsychotics are an increasing proportion of overdose admissions. PMID:26945707

  13. Antipsychotic Medication Prescribing Trends in Children and Adolescents

    Science.gov (United States)

    Harrison, Joyce Nolan; Cluxton-Keller, Fallon; Gross, Deborah

    2013-01-01

    The Food and Drug Administration has approved the use of antipsychotic medications in some children and adolescents with severe emotional and behavioral disorders. However, recent national data show a dramatic rise in off-label and Food and Drug Administration–approved uses of these medications. Of particular note is a twofold to fivefold increase in the use of antipsychotic medications in preschool children, despite little information on their long-term effects. This article describes the trend in pediatric antipsychotic medication use, possible explanations for the increase, implications for children’s health, and recommendations for pediatric providers who work with parents of children and adolescents who seek or receive antipsychotic medication treatments. PMID:22360933

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

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2007-08-01

    Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics

  15. Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia.

    Science.gov (United States)

    Schreiner, Andreas; Aadamsoo, Kaire; Altamura, A Carlo; Franco, Manuel; Gorwood, Philip; Neznanov, Nikolaj G; Schronen, Juan; Ucok, Alp; Zink, Mathias; Janik, Adam; Cherubin, Pierre; Lahaye, Marjolein; Hargarter, Ludger

    2015-12-01

    Relapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome. Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention. This randomized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention. Eligible patients with a recent diagnosis of schizophrenia (within 1-5 years) were randomized 1:1 to paliperidone palmitate (n=376) or oral antipsychotic monotherapy (n=388) and entered a 2-week initial acute oral treatment phase. Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase. Patients were evaluated for relapse, symptoms, functioning, quality of life, treatment satisfaction, and tolerability. In the core treatment phase, time to relapse was significantly longer in the paliperidone palmitate (n=352) compared with the oral antipsychotics arm (n=363): 85% of patients were relapse-free at 469 versus 249 days (P=0.019). Significantly fewer patients receiving paliperidone palmitate met the relapse criteria (52 [14.8%] versus 76 [20.9%, oral antipsychotics]; P=0.032), representing a 29.4% relative risk reduction. For paliperidone palmitate, a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 (P=0.021) and a trend at endpoint (P=0.075) were observed. Functioning improvements were comparable between treatment arms. No new safety signals were identified. The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness. Copyright © 2015 Janssen Pharmaceutica NV. Published by Elsevier B.V. All rights reserved.

  16. An explorative study of school performance and antipsychotic medication

    OpenAIRE

    van der Schans, J.; Vardar, S.; ?i?ek, 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 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 Ne...

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

    Science.gov (United States)

    2016-12-01

    obsessive-4 compulsive and eating disorders [8]. Conventional antipsychotics, e.g., chloropromazine, haloperidol 5 and perphenazine, act primarily as...group. 11 Extrapyramidal Side Effects : movement disorders such as akinesia (decreased voluntary movement), 12 pseudoparkinsonism and akathisia...Endocrine manifestations of eating disorders . J.Clin.Endocrinol.Metab 96, 333-343 60. Jin,H. et al. (2008) Impact of atypical antipsychotic therapy on

  18. Obstetric and Neonatal Outcomes After Antipsychotic Medication Exposure in Pregnancy

    Science.gov (United States)

    Coughlin, Catherine G.; Blackwell, Katherine A.; Bartley, Christine; Hay, Madeleine; Yonkers, Kimberly A.; Bloch, Michael H.

    2015-01-01

    Objective Antipsychotic medications are used by increasing numbers of women of reproductive age. The safety of these medications during pregnancy has not been well-described. We undertook a systematic review and meta-analysis of the adverse obstetric and neonatal outcomes associated with exposure to antipsychotics during pregnancy. Data Sources PubMed, Reprotox, and ClinicalTrials.gov were searched to identify potential studies for inclusion. Methods of Study Selection Case-control or cohort studies estimating adverse birth outcomes associated with antipsychotic exposure during pregnancy were included. Pooled odds ratios (OR) were used for dichotomous outcomes and weighted mean differences (WMD) were used for infant birth weight and gestational age. Thirteen cohort studies, including 6,289 antipsychotic-exposed and 1,618,039 unexposed pregnancies were included. Tabulation, Integration, and Results Antipsychotic exposure was associated with an increased risk of major malformations (Absolute Risk Difference = 0.03, 95% confidence interval [CI] 0.00 – 0.05, p=0.04, Z = 2.06), heart defects (Absolute Risk Difference =0.01, 95% CI 0.00 – 0.01, pantipsychotic medications. Antipsychotic exposure was not associated with risk of large for gestational age births, stillbirth, and spontaneous abortion. Although antipsychotic exposure during pregnancy was associated with increased risk of adverse obstetric and neonatal outcomes, this association does not necessarily imply causation. This analysis was limited by the small number of included studies and limited adjustment in studies for possible confounders. Conclusion Women requiring antipsychotic treatment during pregnancy appear at higher risk of adverse birth outcomes, regardless of causation, and may benefit from close monitoring and minimization of other potential risk factors during pregnancy. PMID:25932852

  19. Peripheral Amino Acid Levels in Schizophrenia and Antipsychotic Treatment

    OpenAIRE

    De Luca, Vincenzo; Viggiano, Emanuela; Messina, Giovanni; Viggiano, Alessandro; Borlido, Carol; Viggiano, Andrea; Monda, Marcellino

    2008-01-01

    Abnormal levels of amino acids have been reported in patients with schizophrenia and have also been investigated as a biomarker to monitor antipsychotic treatment, however results have been inconsistent. The purpose of the present review is to summarize the evidence in the literature of whether amino acid levels can be a biomarker and predict the treatment outcome in schizophrenia. The current review does not support amino acid concentration as a useful biomarker for monitoring antipsychotic ...

  20. ANTIPSYCHOTIC TREATMENT - SIDE-EFFECT AND/OR METABOLIC SYNDROME

    OpenAIRE

    Dadić-Hero, Elizabeta; Ružić, Klementina; Grahovac, Tanja; Žarković Palijan, Tija; Petranović, Duška; Šepić-Grahovac, Dubravka

    2011-01-01

    According to current medical opinion chronic mental diseases such as schizophrenia require life-long treatment. The choice of antipsychotics is an important treatment factor, since their side-effects often influence patients' compliance with treatment. Severe side-effects may cause the patients to reject such treatment, the latter being their right. In case a psychiatrist does not agree with the patient's decision to interrupt his antipsychotic treatment regardless its serious side-e...

  1. Social context and health consequences of the antipsychotics introduction.

    Science.gov (United States)

    Kirkby, Kenneth C

    2005-01-01

    From the vantage point of fifty years after the introduction of antipsychotics to clinical practice, this article examines the social context and health consequences of their introduction. Historical review of literature sources with commentary. The availability of antipsychotics over nearly half a century has powerfully influenced concepts of mental illness, dominant models of care versus control, health outcomes and side effect burdens. The large demand and economic success of antipsychotic medications is an important driver for research and development as well as sophistication in marketing. Regulatory agencies, funders and clinicians are faced with a moving target as indications for use of antipsychotics move well beyond the traditional core of schizophrenia and acute mania into depression, anxiety, behavioral disturbance with dementia and some forms of personality disturbance. The history of antipsychotics and mental illness is arguably being written as forcefully now, in an environment of rapid scientific change, as was the case in the 1960s era of rapid social change when chlorpromazine prompted a shift of emphasis from asylum to community. Psychosis is a challenge to how we interpret and approach our inner experiences and societal structures. Accordingly, it is not surprising that the history of antipsychotic drugs resonates with a lively interplay of social, health and economic issues and an ongoing quest to comprehend mental phenomena and their variants.

  2. 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.

  3. 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.

  4. 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

  5. Zotepine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

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

    2014-01-01

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

  6. Differences in BMI between Mexican and Colombian patients receiving antipsychotics: results from the International Study of Latinos on Antipsychotics (ISLA).

    Science.gov (United States)

    Ng, Bernardo; Camacho, Alvaro; Parra, Katherine; de la Espriella, Ricardo; Rico, Victor; Lozano, Severiano; Troncoso, Mirna; Castilla-Puentes, Ruby C; Cook, Benjamin L; Jimenez, Daniel E

    2018-03-07

    The objective of this study is to examine the association of country of residence with body mass index (BMI) between Mexican and Colombian patients exposed to antipsychotics. We hypothesize that there will be a significant association between country of residence and BMI and that Mexican patients will have higher BMI than their Colombian counterparts. The International Study of Latinos on Antipsychotics (ISLA) is a multisite, international, cross sectional study of adult Latino patients exposed to antipsychotics in two Latin American Countries (i.e. Mexico and Colombia). Data were collected from a total of 205 patients (149 from Mexico and 56 from Colombia). The sites in Mexico included outpatient clinics in Mexicali, Monterrey and Tijuana. In Colombia, data were collected from outpatient clinics in Bogotá. For this study we included patients attending outpatient psychiatric community clinics that received at least one antipsychotic (new and old generation) for the last 3 months. A linear regression model was used to determine the association of country of residence with BMI for participants exposed to an antipsychotic. After controlling for demographics, behaviors, biological and comorbid psychiatric variables, there was a significant difference between Colombia vs. Mexico in the BMI of patients exposed to antipsychotics (β = 4.9; p Mexico and Colombia may reflect differences in prevalence of overweight/obesity at the population level in the respective countries, and highlights the involvement of other risk factors, which may include genetics.

  7. 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.

  8. Neurological Adverse Effects of Antipsychotics in Children and Adolescents.

    Science.gov (United States)

    Garcia-Amador, Margarita; Merchán-Naranjo, Jessica; Tapia, Cecilia; Moreno, Carmen; Castro-Fornieles, Josefina; Baeza, Inmaculada; de la Serna, Elena; Alda, José A; Muñoz, Daniel; Andrés Nestares, Patricia; Cantarero, Carmen Martínez; Arango, Celso

    2015-12-01

    The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and

  9. 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.

  10. 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.

  11. Antipsychotic medication and prefrontal cortex activation : A review of neuroimaging findings

    NARCIS (Netherlands)

    Liemburg, Edith J.; Knegtering, Henderikus; Klein, Hans C.; Kortekaas, Rudie; Aleman, Andre

    Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

    Geers, L.M.; Pozhidaev, I.V.; Ivanova, S.A.; Freidin, M.B.; Cohen, D.; Boiko, A.S.; Osmanova, D.Z.; Fedorenko, O.Y.; Touw, D.J.; Semke, A.V.; Wilffert, B.; Bokhan, N.A.; Loonen, A.J.M.

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  15. 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.

  16. Antipsychotic drugs rapidly induce dopamine neuron depolarization block in a developmental rat model of schizophrenia

    OpenAIRE

    Valenti, Ornella; Cifelli, Pierangelo; Gill, Kathryn M.; Grace, Anthony A.

    2011-01-01

    Repeated administration of antipsychotic drugs to normal rats has been shown to induce a state of dopamine neuron inactivation known as depolarization block, which correlates with the ability of the drugs to exhibit antipsychotic efficacy and extrapyramidal side-effects in schizophrenia patients. Nonetheless, in normal rats depolarization block requires weeks of antipsychotic drug administration, whereas schizophrenia patients exhibit initial effects soon after initiating antipsychotic drug t...

  17. Antipsychotic Medication Prescribing Practices Among Adult Patients Discharged From State Psychiatric Inpatient Hospitals

    Science.gov (United States)

    HOLLEN, VERA; SCHACHT, LUCILLE

    2016-01-01

    Objectives: The goal of this study was to explore antipsychotic medication prescribing practices in a sample of 86,034 patients discharged from state psychiatric inpatient hospitals and to find the prevalence of patients discharged with no antipsychotic medications, on antipsychotic monotherapy, and on antipsychotic polypharmacy. For patients discharged on antipsychotic polypharmacy, the study explored the adjusted rates of antipsychotic polypharmacy, the reasons patients were discharged on antipsychotic polypharmacy, the proportion of antipsychotic polypharmacy by mental health disorder, and the characteristics associated with being discharged on antipsychotic polypharmacy. Methods: This cross-sectional study analyzed all discharges for adult patients (18 to 64 y of age) from state psychiatric inpatient hospitals between January 1 and December 31, 2011. The relationship among variables was explored using χ2, t test, and analysis of variance. Logistic regression was used to determine predictors of antipsychotic polypharmacy. Results: The prevalence of antipsychotic polypharmacy was 12%. Of the discharged patients receiving at least 1 antipsychotic medication (adjusted rate), 18% were on antipsychotic polypharmacy. The strongest predictors of antipsychotic polypharmacy being prescribed were having a diagnosis of schizophrenia and a length of stay of 90 days or more. Patients were prescribed antipsychotic polypharmacy primarily to reduce their symptoms. Conclusions: Antipsychotic polypharmacy continues at a high enough rate to affect nearly 10,000 patients with a diagnosis of schizophrenia each year in state psychiatric inpatient hospitals. Further analysis of the clinical presentation of these patients may highlight particular aspects of the illness and its previous treatment that are contributing to practices outside the best-practice guideline. An increased understanding of trend data, patient characteristics, and national benchmarks provides an opportunity for

  18. Risperidone versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    : To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...... increased as the annual median number of defined daily doses (DDD) increased from 33.3 to 42.0 DDD. CONCLUSIONS: The changing patterns of psychotropic drug use may be caused by warnings against use of antipsychotics. Further research is needed to explore the implications for patient safety....

  20. Diabetic ketoacidosis associated with antipsychotic drugs: case reports and a review of literature.

    Science.gov (United States)

    Vuk, Antonia; Kuzman, Martina Rojnic; Baretic, Maja; Osvatic, Martina Matovinovic

    2017-06-01

    Second generation antipsychotics (SGAs) are associated with metabolic disturbances. Diabetic ketoacidosis (DKA) is a rare, but potentially fatal sign of acute glucose metabolism dysregulation linked to the use of SGAs. The aims of this article are to present patients with a history of psychotic disorders and of severe metabolic diabetic ketoacidosis, possibly associated with the use of antipsychotics, and to review the current literature on the topic of antipsychotic-induced DKA. PubMed/Medline and EBSCO databases were searched using the keywords: diabetic ketoacidosis, antipsychotics, atypical antipsychotics, second generation antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride and haloperidol. Case reports, case series and reviews of case series were included in the review. The majority of patients who developed DKA following treatment with antipsychotics were treated with olanzapine and clozapine in monotherapy or in combination with other antipsychotics. DKA mostly occurred in the first six months of antipsychotic treatment. Other risk factors included insulin resistance prior to antipsychotic treatment, male gender and middle age. Clinicians should consider the risk of DKA when starting treatment with SGAs. Preventive measures for patients with psychotic disorders using antipsychotics should include regular assessment of risk factors and screening for diabetes before and after administering antipsychotics, especially in the first months of treatment. Whenever possible, polypharmacy should be avoided.

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

    Science.gov (United States)

    Lunsky, Yona; Elserafi, Jonny

    2012-01-01

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

  2. Initiation of antipsychotic treatment by general practitioners. A case-control study

    NARCIS (Netherlands)

    Boonstra, Geartsje; Grobbee, Diederick E; Hak, Eelko; Kahn, René S; Burger, Huibert

    RATIONALE, AIMS AND OBJECTIVES: Antipsychotics are approved treatment for severe conditions and have serious side effects. Antipsychotics are often prescribed off-label. Although a substantial proportion of antipsychotics are prescribed in primary care, it is largely unknown what motivates the

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

    Science.gov (United States)

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

    2016-09-21

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

  4. Antipsychotic prescribing patterns during and after critical illness: a prospective cohort study.

    Science.gov (United States)

    Tomichek, Jason E; Stollings, Joanna L; Pandharipande, Pratik P; Chandrasekhar, Rameela; Ely, E Wesley; Girard, Timothy D

    2016-11-24

    Antipsychotics are used to treat delirium in the intensive care unit (ICU) despite unproven efficacy. We hypothesized that atypical antipsychotic treatment in the ICU is a risk factor for antipsychotic prescription at discharge, a practice that might increase risk since long-term use is associated with increased mortality. After excluding patients on antipsychotics prior to admission, we examined antipsychotic use in a prospective cohort of ICU patients with acute respiratory failure and/or shock. We collected data on medication use from medical records and assessed patients for delirium using the Confusion Assessment Method for the ICU. Using multivariable logistic regression, we analyzed whether age, delirium duration, atypical antipsychotic use, and discharge disposition (each selected a priori) were independent risk factors for discharge on an antipsychotic. We also examined admission Acute Physiology and Chronic Health Evaluation (APACHE) II score, haloperidol use, and days of benzodiazepine use in post hoc analyses. After excluding 18 patients due to prior antipsychotic use and three who withdrew, we included 500 patients. Among 208 (42%) treated with an antipsychotic, median (interquartile range) age was 59 (49-69) years and APACHE II score was 26 (22-32), characteristics that were similar among antipsychotic nonusers. Antipsychotic users were more likely than nonusers to have had delirium (93% vs. 61%, p antipsychotic users, 172 survived to hospital discharge, and 42 (24%) of these were prescribed an antipsychotic at discharge. Treatment with an atypical antipsychotic was the only independent risk factor for antipsychotic prescription at discharge (odds ratio 17.6, 95% confidence interval 4.9 to 63.3; p antipsychotic. In this study, antipsychotics were used to treat nearly half of all antipsychotic-naïve ICU patients and were prescribed at discharge to 24% of antipsychotic-treated patients. Treatment with an atypical antipsychotic greatly increased the

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Alex T. Raben

    2018-01-01

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

  7. Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia.

    Science.gov (United States)

    Kołaczkowski, Marcin; Mierzejewski, Paweł; Bienkowski, Przemyslaw; Wesołowska, Anna; Newman-Tancredi, Adrian

    2014-06-01

    Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD.

  8. Quetiapine, clozapine, and olanzapine in the treatment of tardive dyskinesia induced by first-generation antipsychotics: a 124-week case report.

    Science.gov (United States)

    Sacchetti, E; Valsecchi, P

    2003-11-01

    Our report of a patient with severe tardive dyskinesia (TD) who has been exposed to both typical antipsychotic and clozapine, olanzapine and quetiapine during a 124-week follow-up period supports the possible beneficial effect of atypical antipsychotics on pre-existing symptoms of TD. Persistently high AIMS scores during all the periods of treatment with typical antipsychotics contrast strongly with the drop in scores that occurs in strict chronological sequence after switching to both clozapine (45%), olanzapine (27.8%) and quetiapine (85%). Since the reversal to haloperidol from the three atypical agents was systemically associated with a return to high AIMS scores, it seems likely that the improvement noted with clozapine, olanzapine and quetiapine represents a temporary symptomatic effect rather than a sustained resolution of the disorder. The olanzapine-clozapine-quetiapine rank order of increasing effectiveness against TD symptoms suggests that this property, although shared by the atypical antipsychotics, is to some degree drug-specific. Patient- and/or drug-dependent mechanisms may be involved in this gradient of effect.

  9. 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.

  10. 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...... use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of event. Overall treatment with any antipsychotic was associated with OHCA (odds ratio [OR]= 1.53, 95...

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    of high dose prescriptions. We also noted a change in the patterns of antipsyhotics prescribed at this center. In a previous study on psychotropic drug prescribing at this hospital in 2007,[21] it was found that haloperidol was the most commonly prescribed antipsychotic drug, followed by chlorpromazine and trifluoperazine.

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

    African Journals Online (AJOL)

    Atypicals, are very expensive and unaffordable to the majority of patients in the study setting. This indicates the need for measures to reduce cost of newer psychotropic drugs, to increase their availability and use for enhanced quality of life of mentally ill patients in Nigeria. Keywords; :prescription pattern, antipsychotics, ...

  14. 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.

  15. Imaging as tool to investigate psychoses and antipsychotics

    NARCIS (Netherlands)

    Booij, Jan; van Amelsvoort, Thérèse

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  17. Seclusion and the use of antipsychotics in hospitalized psychiatric patients

    NARCIS (Netherlands)

    Stolker, JJ; Hugenholtz, GWK; Heerdink, ER; Nijman, HLI; Leufkens, HGM; Nolen, WA

    2005-01-01

    The purpose of this study is to measure the incidence of seclusion, identify possible determinants of seclusion and to gain insight into the use of antipsychotics before and after seclusion in acutely admitted patients. In The Netherlands, special treatment methods including seclusion and

  18. Corrected QT changes during antipsychotic treatment of children and adolescents

    DEFF Research Database (Denmark)

    Jensen, Karsten Gjessing; Juul, Klaus; Fink-Jensen, Anders

    2015-01-01

    covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n...

  19. Antipsychotic Effect of the Leaves of Stachytarpheta Cayennensis ...

    African Journals Online (AJOL)

    The antipsychotic effect of the extracts of the leaves of Stachytarpheta cayennensis was examined following ethnomedicinal claims for its use in the management of mental illness in Nigeria, Ghana and other tropical parts of the globe. The apomorphine and amphetamine-induced stereotyped behavior models were used in ...

  20. Development of a Patient-Centered Antipsychotic Medication Adherence Intervention

    Science.gov (United States)

    Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia

    2014-01-01

    Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…

  1. Antipsychotic effect of aqueous stem bark extract of ...

    African Journals Online (AJOL)

    The study of antipsychotic efect of the aqueous stem bark extract of Amblygonocarpus andongensis was carried out on amphetamine induced psychosis in 42 Wister albino rats weighingbetween 105 and 3052g using two indices feeding and locomotor activity. Twelve out of the 42 rats were divided into two groups; six per ...

  2. 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…

  3. Antipsychotic poisoning in young children: a systematic review.

    Science.gov (United States)

    Isbister, Geoffrey K; Balit, Corrine R; Kilham, Henry A

    2005-01-01

    The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children

  4. [Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

    Science.gov (United States)

    Jaramillo González, Luis Eduardo; Gómez Restrepo, Carlos; García Valencia, Jenny; de la Hoz Bradford, Ana María; Ávila-Guerra, Mauricio; Bohórquez Peñaranda, Adriana

    2014-01-01

    To determine the indications of long-acting antipsychotic injection and what its effectiveness and safety in adult patients with schizophrenia during the treatment maintenance phase. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The literature review shows that the evidence has moderate to low quality. 8 articles were used. The risk of relapse was lower with depot risperidone and paliperidone palmitate when compared with placebo. For the risk of hospitalizations comparing depot antipsychotics (APD) versus oral AP, the result is inconclusive. Globally the second-generation APD had a lower risk of discontinuation when compared with placebo. The second generation AP had higher risk of extrapyramidal syndromes than placebo, as in the use of antiparkinsonian. The comparison of second-generation AP injections versus placebo showed an increased risk of early weight gain. The use of depot antipsychotics in the maintenance phase of adult patients diagnosed with schizophrenia is recommended if there is no adherence to oral antipsychotics as the patient's preference. It is not recommended depot antipsychotics in the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  5. Selectivity of action of typical and atypical anti-psychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI).

    Science.gov (United States)

    Wettstein, J G; Host, M; Hitchcock, J M

    1999-04-01

    1. There has been considerable research in the field of schizophrenia over the past few years with emphasis on the discovery of better drugs, particularly those with 5-HT2 antagonist activity. 2. In an effort to enhance identification of such compounds and to further understand the contribution of 5-HT2 activity to the effects of antipsychotic drugs, a series of conventional, atypical and purported antipsychotic compounds were assessed as antagonists of DOI-induced behaviors in rats. 3. DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride) is an hallucinogen having high affinity and selectivity as an agonist at 5-HT2A/2C receptors. Over a 30-min period after injection, DOI (0.3-10.0 mg/kg; i.p.) produced dose-related behavioral effects including head-and-body shakes, forepaw tapping and skin-jerks. Effects of the antipsychotic drugs and other compounds (30 min pretreatment; i.p.) were examined against a fixed dose of DOI (3.0 mg/kg). 4. In a dose-dependent manner, M100907 (MDL 100,907), risperidone, haloperidol, clozapine, iloperidone, olanzapine, amperozide, remoxipride, ritanserin and the neurotensin agonist NT1 (N alpha MeArg-Lys-Pro-Trp-Tle-Leu) antagonized each of the three behavioral effects of DOI. Drugs attenuating the head-and-body shakes were equally effective in blocking both forepaw tapping and skin-jerks indicating that these behaviors are mediated by similar mechanisms. The following compounds had either inconsistent or no effect on the DOI-induced behaviors: SB 200646A, citalopram, imipramine, fluoxetine, morphine, CP 99994, diazepam, ondansetron and SKF 97541. 5. The data show that antipsychotic agents, as a drug class, effectively block the effects of DOI. These actions are selective, as a series of nine non-antipsychotic and centrally-acting drugs were generally inactive in the procedure.

  6. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis.

    Science.gov (United States)

    Mizuno, Yuya; Suzuki, Takefumi; Nakagawa, Atsuo; Yoshida, Kazunari; Mimura, Masaru; Fleischhacker, Walter Wolfgang; Uchida, Hiroyuki

    2014-11-01

    Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to -3.17 kg (95% CI: -4.44 to -1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For

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

    Directory of Open Access Journals (Sweden)

    Hülya Ertekin

    2016-08-01

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

  8. Length of mechanical restraint following haloperidol injections versus oral atypical antipsychotics for the initial treatment of acute schizophrenia: a propensity-matched analysis from the Japanese diagnosis procedure combination database.

    Science.gov (United States)

    Nakamura, Mitsuhiro; Yasunaga, Hideo; Haraguchi, Tadashi; Ando, Shuntaro; Sugihara, Toru; Horiguchi, Hiromasa; Ohe, Kazuhiko; Matsuda, Shinya; Fushimi, Kiyohide

    2013-10-30

    Differences in effectiveness between haloperidol injection and oral atypical antipsychotics in the acute-phase treatment of schizophrenia are not well examined. We retrospectively investigated whether these treatment options affected the length of mechanical restraint. We used the Japanese Diagnosis Procedure Combination Database to identify schizophrenia patients who were involuntarily hospitalized and receiving mechanical restraint between July and December, 2006-2009. Data included patient demographics, use of antipsychotics, and number of days on which patients underwent mechanical restraint. Propensity score matching was performed to compare the number of days of mechanical restraint between the haloperidol injection group and the oral atypical antipsychotics group. We used survival analysis to examine whether the initial difference in treatment affected the number of days of mechanical restraint. Cox regression was performed to compare the concurrent effects of various factors. Among 1731 eligible patients, 574 were treated with haloperidol injections and 420 with atypical antipsychotics. Matching produced 274 patients in each group. Cox regression analysis showed that the initial therapeutic agents did not significantly affect the number of days of mechanical restraint. The results indicate that atypical antipsychotics were as effective as haloperidol injections in the acute-phase treatment of schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Antipsychotic polypharmacy in clozapine resistant schizophrenia: a randomized controlled trial of tapering antipsychotic co-treatment

    Directory of Open Access Journals (Sweden)

    Jari Tiihonen

    2012-01-01

    Full Text Available There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N = 15 who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.

  10. Antipsychotic Polypharmacy and Its Relation to Metabolic Syndrome in Patients With Schizophrenia: An Egyptian Study.

    Science.gov (United States)

    Aly El-Gabry, Dina M; Abdel Aziz, Karim; Okasha, Tarek; Azzam, Hanan; Okasha, Ahmed

    2018-02-01

    Few studies have examined the relationship between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. Some studies suggest that antipsychotic polypharmacy may be associated with greater metabolic risk, whereas other studies suggest that this is uncertain. To date, there have been no studies in Egypt or the Arab world that have investigated this relationship. We sought to compare subjects with schizophrenia receiving antipsychotic polypharmacy and monotherapy as regards metabolic outcomes and to investigate medication-related factors associated with metabolic syndrome. We recruited 118 subjects with schizophrenia and compared between those receiving antipsychotic polypharmacy (86 subjects) and monotherapy (32 subjects) as regards demographic, clinical, metabolic, and antipsychotic medication characteristics. We examined the effect of antipsychotic-related factors an outcome of metabolic syndrome. The prevalence of metabolic syndrome in our sample was 38.1%. Except for gender, there was no statistically significant difference as regards demographic and clinical characteristics, rates of metabolic syndrome, or for individual metabolic parameters. We found a statistically significant difference (P antipsychotics (oral and depot) and a number of individual antipsychotic medications. Using logistic regression, receiving haloperidol depot was the only antipsychotic-related factor predictive for metabolic syndrome. The prevalence of metabolic syndrome does not differ in schizophrenia whether patients are receiving polypharmacy and monotherapy nor do they differ for individual metabolic parameters. Most antipsychotic-related characteristics did not predict for metabolic syndrome.

  11. Antipsychotic-induced sensitization and tolerance: Behavioral characteristics, developmental impacts, and neurobiological mechanisms.

    Science.gov (United States)

    Li, Ming

    2016-08-01

    Antipsychotic sensitization and tolerance refer to the increased and decreased drug effects due to past drug use, respectively. Both effects reflect the long-term impacts of antipsychotic treatment on the brain and result from the brain's adaptive response to the foreign property of the drug. In this review, clinical evidence of the behavioral aspect of antipsychotic sensitization and tolerance is selectively reviewed, followed by an overview of preclinical literature that examines these behavioral characteristics and the related pharmacological and nonpharmacological factors. Next, recent work on the developmental impacts of adolescent antipsychotic sensitization and tolerance is presented and recent research that delineates the neurobiological mechanisms of antipsychotic sensitization and tolerance is summarized. A theoretical framework based on "drug learning and memory" principles is proposed to account for the phenomena of antipsychotic sensitization and tolerance. It is maintained that antipsychotic sensitization and tolerance follow basic principles of learning or acquisition ("induction") and memory ("expression"). The induction and expression of both effects reflect the consequences of associative and nonassociative processing and are strongly influenced by various pharmacological, environmental, and behavioral factors. Drug-induced neuroplasticity, such as functional changes of striatal dopamine D2 and prefrontal serotonin (5-HT)2A receptors and their mediated signaling pathways, in principle, is responsible for antipsychotic sensitization and tolerance. Understanding the behavioral characteristics and neurobiological underpinnings of antipsychotic sensitization and tolerance has greatly enhanced our understanding of mechanisms of antipsychotic action, and may have important implications for future drug discovery and clinical practice. © The Author(s) 2016.

  12. Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations

    Science.gov (United States)

    Eum, Seenae; Lee, Adam M.; Bishop, Jeffrey R.

    2016-01-01

    Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed. PMID:27757066

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

    Science.gov (United States)

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

    2012-05-01

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

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

    Science.gov (United States)

    Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

    2016-01-01

    Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

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

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

      The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side-effe...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ......-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...

  16. QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

    DEFF Research Database (Denmark)

    Elliott, Anja Friis; Johan Mørk, Thibault; Højlund, Mikkel

    2018-01-01

    Objective: Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged...... by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia......-up until June of 2015. Data were collected from clinical interviews and clinical case records. Results: Electrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics...

  17. [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.

  18. 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...human preadipocytes which were induced to differentiate in culture. Cells were incubated with the drugs for 72 hrs, and after media replacement...conditioned media were collected for 4 hrs and analyzed for glycerol by a colorimetric assay. As evident in Fig 4, Olanzapine caused dose-dependent

  19. Sleepwalking, a possible side effect of antipsychotic medication.

    Science.gov (United States)

    Seeman, Mary V

    2011-03-01

    Two case examples and a review of the sleep literature illustrate the potential of antipsychotic medication to trigger sleepwalking episodes in the context of schizophrenia. Causative hypotheses are briefly reviewed, as well as risk factors, differential diagnosis, and management. Sleepwalking may contribute to delusions, aggression, and accidental suicide. It is important to investigate sleep disorders in schizophrenia. They are not rare and may contribute to behavior that increases the stigma and isolation of individuals with schizophrenia.

  20. Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

    OpenAIRE

    Chen, Jiezhong; Huang, Xu-Feng; Shao, Renfu; Chen, Chen; Deng, Chao

    2017-01-01

    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 treat...

  1. 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.)

  2. 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.

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

    Gomez, Seth; Dopheide, Julie

    2016-11-01

    Early recognition and treatment of agitated patients is essential to avoid violence in the psychiatric emergency department (ED). Antipsychotics have established efficacy in managing agitation, yet little is known about how the choice of initial antipsychotic impacts time to repeat use and length of stay (LOS) in the psychiatric ED. To describe the impact of initial antipsychotic selection on time to repeat use and LOS in the psychiatric ED. A chart review identified 388 cases in which patients were administered an antipsychotic for agitation in the psychiatric ED between July 1 and August 31, 2014. Time to repeat use and LOS were compared for intramuscular (IM) haloperidol, other IM antipsychotics, and oral second-generation antipsychotics (SGAs) using the Kruskal-Wallis or Wilcoxon-Mann-Whitney test. Of the 388 cases, 31% (n=122) required repeat medications. Mean time to repeat use for IM haloperidol was 20.1±18.4 hours, which was not significantly different from mean time to repeat use in the groups receiving other IM antipsychotics or oral SGAs (P=0.35). The mean LOS was 29.7±28.7 hours for IM haloperidol, 30.3±36.9 hours for other IM antipsychotics, and 22.6±28.0 hours for oral SGAs. Significant differences in LOS between repeat and nonrepeat users of IM haloperidol and other IM antipsychotics were observed, but not among those who received oral SGAs. Mean time to repeat use ranged from 14 to 20 hours with IM haloperidol, other IM antipsychotics, and oral SGAs without significant differences in time to repeat use in the 3 different groups. Repeat users of IM antipsychotics had a significantly longer LOS in the ED compared with nonrepeat users of IM antipsychotics. However, patients who were initially administered oral SGAs did not have longer LOS in the ED even if a repeat dose was given.

  5. Severe tardive dystonia on low dose short duration exposure to atypical antipsychotics: Factors explored

    OpenAIRE

    Nilanjan C Chandra; Shabina A Sheth; Ritambhara Y Mehta; Kamlesh R Dave

    2017-01-01

    Tardive dystonia (TD) is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics 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 a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose sh...

  6. Trends in antipsychotic prescriptions for Japanese outpatients during 2006-2012: a descriptive epidemiological study.

    Science.gov (United States)

    Kochi, Kenji; Sato, Izumi; Nishiyama, Chika; Tanaka-Mizuno, Sachiko; Doi, Yuko; Arai, Masaru; Fujii, Yosuke; Matsunaga, Toshiyuki; Ogawa, Yusuke; Furukawa, Toshi A; Kawakami, Koji

    2017-06-01

    This study aimed to assess the trends in antipsychotic prescriptions for outpatients in Japan, where a community-based approach to mental healthcare is emphasized. This descriptive epidemiological study used claims data from 1038 community pharmacies across Japan. Outpatients who were ≥18 years old and receiving their initial antipsychotic prescription during 2006-2012 were evaluated. The annual trends were reported for monotherapies, polypharmacy, antipsychotic doses, and the concurrent prescription of psychotropic medications. The 152 592 outpatients included 101 133 (66%) adults (18-64 years old) and 51 459 (34%) older adults (≥65 years old). Among the adults, second-generation antipsychotic monotherapy prescriptions increased from 49% in 2006 to 71% in 2012, first-generation antipsychotic monotherapy prescriptions decreased from 29 to 14%, and antipsychotic polypharmacy decreased from 23 to 15%, respectively. Among the older adults, second-generation antipsychotic monotherapy prescriptions increased from 64 to 82%, first-generation antipsychotic monotherapy prescriptions decreased from 29 to 12%, and antipsychotic polypharmacy decreased from 7 to 6%, respectively. During the study period, >80% of the adults and >90% of the older adults received antipsychotics at risperidone-equivalent doses of antipsychotics for 70, 33, 20, 20, and 0.3% of the adults and for 43, 16, 19, 8, and 16% of the older adults, respectively. The present study evaluated large-scale claims-based datasets and found that high-dose prescriptions and antipsychotic polypharmacy among Japanese outpatients were not as prevalent as has been previously thought. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. 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.

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

    Science.gov (United States)

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

    2014-08-01

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

  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. Antipsychotic prescribing in care homes before and after launch of a national dementia strategy: an observational study in English institutions over a 4-year period

    Science.gov (United States)

    Szczepura, Ala; Owen, David W; Palmer, Thomas; Muhammad, Tariq; Clark, Michael D

    2016-01-01

    Objectives To assess associations between the launch of the National Dementia Strategy (NDS) and antipsychotic prescribing in long-term residential care (LTC) in England. Setting and participants Retrospective analysis of prescribing patterns in 616 LTC institutions (31 619 residents) following launch of the NDS, using information from electronic medicines management system. Primary and secondary outcome measures Antipsychotic prescribing point prevalence (PP) for all residents in a cross section of LTC settings over a 4-year period following NDS launch. Secondary outcomes included dosages, length of treatment and use of recommended second-generation antipsychotics (SGAs) versus first-generation antipsychotics (FGAs). Associations between facility-level PP values and institutional characteristics, resident demographics were explored. Variations across geographical areas examined. Prescription net ingredient costs calculated. Results No statistically significant difference was observed in overall prescribing rates over the 4-year period (Kolmogorov-Smirnov (KS) test p=0.60), and there was no significant shift towards newer SGAs (KS test p=0.32). Dosages were above the maximum indicated in only 1.3% of cases, but duration of prescribing was excessive in 69.7% of cases. Care homes in the highest prescribing quintile were more likely to be located in a deprived area (rate ratio (Q5/Q1) RR=5.89, 95% CI 4.35 to 7.99), registered for dementia (RR=3.38, 95% CI 3.06 to 3.73) and those in the lowest quintile were more likely to be served by a single general practitioner (GP) practice (RR=0.48; 95% CI 0.37 to 0.63); pantipsychotics was £65.6 per person resident (2012 prices). Conclusions The NDS in England was not associated with reduced PP levels or the types of antipsychotic prescribing in care homes. Further research is needed to explore why. Clear standards specifying recommended agents, dosages and length of treatment, together with routine monitoring and greater

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

    Angelini, A; Ciofani, G; Conti, P

    2015-01-01

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

  13. 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.

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

    DEFF Research Database (Denmark)

    Kristensen, Diana; Hageman, Ida; Bauer, Jeanett

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    for ziprasidone and unclear for asenapine. Adverse reaction profiles varied substantially among the investigated antipsychotics and were largely consistent with prior findings in adults. Protocol registration information-Antipsychotic Treatment for Children With Schizophrenia Spectrum Disorders: Network Meta......-Analysis of Randomised Trials; https://www.crd.york.ac.uk/PROSPERO/; CRD42013006676....

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  19. Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder

    Science.gov (United States)

    Wink, Logan K.; Adams, Ryan; Pedapati, Ernest V.; Dominick, Kelli C.; Fox, Emma; Buck, Catherine; Erickson, Craig A.

    2017-01-01

    Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of…

  20. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte; Rasmussen, Hans

    2010-01-01

    enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia. METHODS: We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched...

  1. Nature and Quality of Antipsychotic Prescribing Practice in UK Psychiatry of Intellectual Disability Services

    Science.gov (United States)

    Paton, C.; Flynn, A.; Shingleton-Smith, A.; McIntyre, S.; Bhaumik, S.; Rasmussen, J.; Hardy, S.; Barnes, T.

    2011-01-01

    Background: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed…

  2. Exploring regional variation in antipsychotic coprescribing practice: a Danish questionnaire survey

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter N.; Nordentoft, Merete

    2010-01-01

    The pharmacologic treatment of schizophrenia is characterized by excessive use of antipsychotic polypharmacy, which reflects a gap between evidence and practice. The aim of the present study was to investigate regional differences in treatment setting characteristics and in physician and nurse...... attitudes toward antipsychotic polypharmacy and clinical guidelines....

  3. Representation of People with Intellectual Disabilities in Randomised Controlled Trials on Antipsychotic Treatment for Behavioural Problems

    Science.gov (United States)

    Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.

    2011-01-01

    Background: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs.…

  4. Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

    Science.gov (United States)

    Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

    2016-01-01

    Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

  5. Antipsychotic Medication and People with Intellectual Disabilities: Their Knowledge and Experiences

    Science.gov (United States)

    Crossley, Rachel; Withers, Paul

    2009-01-01

    Background: Antipsychotics are the most frequently prescribed psychotropic medication for people with intellectual disabilities. Many people are prescribed this medication for "challenging behaviours" without having had a formal diagnosis of a psychiatric disorder. Antipsychotics have been reported to have severe side-effect profiles, which can…

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

    Science.gov (United States)

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

    2010-01-01

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

  7. Antipsychotic Use and Metabolic Monitoring in Individuals with Developmental Disabilities Served in a Medicaid Medical Home

    Science.gov (United States)

    Ruiz, Lisa M.; Damron, Mackenzie; Jones, Kyle B.; Weedon, Dean; Carbone, Paul S.; Bakian, Amanda V.; Bilder, Deborah A.

    2016-01-01

    This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4%) were taking antipsychotics, which was associated with male gender (p = 0.01), intellectual disability with and without autism…

  8. The efficacy of antipsychotics for prolonged delirium with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Asano S

    2017-11-01

    Full Text Available Satoko Asano, Yasuto Kunii, Hiroshi Hoshino, Yusuke Osakabe, Tetsuya Shiga, Shuntaro Itagaki, Itaru Miura, Hirooki Yabe Department of Neuropsychiatry, School of Medicine Fukushima Medical University, Fukushima, Japan Aim: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization.Methods: We extracted all new inpatients (n=523 consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an “early improvement group” in which delirium resolved in ≤3 days after starting psychiatric medication, and a “prolonged group” with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2, we defined an “early improvement group with renal dysfunction” in which delirium resolved in ≤3 days after starting psychiatric medication and a “prolonged group with renal dysfunction” with delirium lasting for >3 days. We then examined differences between groups for different categorical variables.Results: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction.Conclusion: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction. Keywords: antipsychotic, prolonged delirium, chronic kidney disease, pharmacokinetics 

  9. Disruption of conditioned reward association by typical and atypical antipsychotics.

    Science.gov (United States)

    Danna, C L; Elmer, G I

    2010-07-01

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

  10. New users of antipsychotic medication: A population-based cohort study of occupational outcome measures in relation to antipsychotic on-label and off-label prescribing practices

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    BACKGROUND: Treatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing...... patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy. METHODS: Register-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare...... payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. RESULTS: The majority of new antipsychotic users...

  11. Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

    DEFF Research Database (Denmark)

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

    2014-01-01

    INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative...... allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently...

  12. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.

    2011-01-01

    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...... 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...

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

    Science.gov (United States)

    Papola, D; Gastaldon, C; Ostuzzi, G

    2018-06-01

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

  14. The comparison of glucose and lipid metabolism parameters in drug-naïve, antipsychotic-treated, and antipsychotic discontinuation patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Wu X

    2014-07-01

    Full Text Available Xiaoli Wu,1,2 Zeping Huang,3 Hongying Han,2 Zhiyong Zhong,2 Zhaoyu Gan,2 Xiaofeng Guo,1 Feici Diao,2 Zili Han,2 Jingping Zhao1 1Mental Health Institute of the Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, People’s Republic of China; 2Psychiatry Department, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Ultrasound Department, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Background: Although many studies have reported that glucose and lipid metabolism disorders are a significant side effect associated with the use of antipsychotic drugs, the characteristics of glucose and lipid metabolism disorders in patients with schizophrenia who are taking antipsychotic drugs remain poorly understood, and the possible effects that antipsychotic discontinuation may have on glucose and lipid metabolism remain unclear. Methods: The sample consisted of 131 Chinese patients with schizophrenia, including 70 first-episode, drug-naïve patients; 33 patients who had received continuous antipsychotic drug treatment for ≥1 year prior to the beginning of the study; and 28 patients who had discontinued antipsychotic drug treatment for ≥3 months prior to the beginning of study. We compared the glucose and lipid metabolic parameter levels among the three groups of patients with schizophrenia. All assessments were performed upon hospital admission. Results: The characteristics of glucose and lipid metabolism disorders in Chinese patients with schizophrenia who are taking antipsychotic drugs included significant augmentation of the body mass index and waist circumference, significantly higher levels of fasting plasma insulin and insulin resistance, and significantly lower plasma high-density lipoprotein cholesterol levels. Antipsychotic discontinuation

  15. Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis

    DEFF Research Database (Denmark)

    Baandrup, Lone; Sørensen, Jan; Lublin, Henrik Kai Francis

    2012-01-01

    (2007: 25% higher costs; 2008: 17% higher costs) when adjusting for potential confounders and risk factors. A subgroup analysis suggested that the excessive costs associated with antipsychotic polypharmacy were partly accounted for by the functional level of the patients. CONCLUSION: The results......OBJECTIVE: To investigate the association of antipsychotic polypharmacy in schizophrenia with cost of primary and secondary health service use. METHOD: Comparative analysis of health service cost for patients prescribed antipsychotic polypharmacy versus antipsychotic monotherapy. Resource...... utilisation and costs were described using central Danish registers for a 2 year period (2007-2008). We included patients attached to one of two Danish psychiatric referral centres in 1 January 2008 and/or 1 January 2009. Their prescribed treatment with either antipsychotic polypharmacy or monotherapy...

  16. 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.

  17. Antipsychotic efficacy in psychosis with co-morbid cannabis misuse: A systematic review.

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    Wilson, Robin P; Bhattacharyya, Sagnik

    2016-02-01

    The prevalence of cannabis use in patients with psychotic mental illness is known to be high and is suspected to exacerbate symptoms and worsen prognosis. We aimed to evaluate evidence of antipsychotic efficacy in reducing the burden of psychotic symptoms and cannabis use in individuals with psychotic mental illness and co-morbid cannabis use. A systematic review was conducted of antipsychotic treatment in those with psychotic mental illness and co-morbid cannabis use. Quality of evidence for each study and outcomes were rated using the 'GRADE' approach. Twenty-two studies were identified: 13 experimental and 9 observational, including a total sample of 1543 patients, 761 of whom had a diagnosed cannabis use disorder. The most frequent antipsychotics compared were risperidone, olanzapine and clozapine with olanzapine, risperidone and haloperidol. No clear differences between antipsychotics were demonstrated. Future studies are needed to confirm whether clozapine is superior to other antipsychotics in reducing cannabis use. © The Author(s) 2015.

  18. New-onset treatment-dependent diabetes mellitus and hyperlipidemia associated with atypical antipsychotic use in older adults without schizophrenia or bipolar disorder.

    Science.gov (United States)

    Erickson, Sara C; Le, Lisa; Zakharyan, Armen; Stockl, Karen M; Harada, Ann S M; Borson, Soo; Ramsey, Scott D; Curtis, Bradford

    2012-03-01

    To examine the association between atypical antipsychotic medications and incident treatment for diabetes mellitus or hyperlipidemia in elderly adults without diagnoses of schizophrenia or bipolar disorder. Two case-control studies using medical and pharmacy claims data. United States managed care population from multiple insurance plans. Individuals aged 65 and older enrolled in a Medicare Advantage or commercial (health maintenance organization) managed care health plan in the western United States with no claims indicating diagnosis of schizophrenia or bipolar disorder in the 1 year pre-index period. Cases were defined as persons newly initiated on an antidiabetic (n = 13,075) or antihyperlipidemic (n = 63,829) medication on the index date. For the new diabetes mellitus analysis, 65,375 controls were matched to cases based on age, sex, health-plan type, and index date year. In the new hyperlipidemia analysis, 63,829 controls were matched to cases based on the same variables. Conditional logistic regressions were performed to determine the odds of initiated antidiabetic or antihyperlipidemic medication for participants exposed to atypical antipsychotics compared with those with no exposure. The models included comorbidities possibly associated with the outcome. Exposure to atypical antipsychotics was associated with significantly greater adjusted odds of starting an antidiabetic medication (1.32, 95% confidence interval (CI) = 1.10-1.59) but significantly lower odds of starting an antihyperlipidemic medication (0.76, 95% CI = 0.67-0.87). Use of atypical antipsychotics in older adults for conditions other than schizophrenia and bipolar disorder was associated with incident treatment of diabetes mellitus but not of hyperlipidemia, suggesting that older adults may be susceptible to the adverse metabolic consequences of these agents. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  19. Pneumonia following antipsychotic prescriptions in electronic health records: a patient safety concern?

    Science.gov (United States)

    Star, Kristina; Bate, Andrew; Meyboom, Ronald HB; Edwards, I Ralph

    2010-01-01

    Background In screening the Intercontinental Medical Statistics (IMS) Health Disease Analyzer database of GP records from the UK, an increased registration of pneumonia subsequent to the prescription of some antipsychotic medicines was identified. Aim To investigate the temporal pattern between antipsychotic prescriptions and pneumonia with respect to age, type of pneumonia and other chest infections, and antipsychotic class. Design of study Self-controlled cohort analysis. Setting Electronic health records from the UK IMS Health Disease Analyzer database. Method Three groups of pneumonia-related International Classification of Diseases (ICD)-10 terms and prescriptions of atypical and conventional antipsychotic medicines were studied. Separate analyses were carried out for patients aged a65 years. The observed rate of pneumonia terms registered in different time periods in connection to antipsychotic prescriptions was contrasted to the overall rate of pneumonia terms relative to prescriptions of other drugs in the same dataset. Results In patients aged ≥65 years, an increased registration of a group of terms defined as ‘acute chest infections’, after atypical antipsychotic prescriptions, was identified. The corresponding increase after conventional antipsychotic prescriptions was much smaler. Bronchopneumonia had a striking increase after both atypical and conventional antipsychotic prescriptions, and was commonly recorded with fatal outcome. Few registrations of hypostatic pneumonia were noted. Patients aged atypical antipsychotic prescriptions in older people seen in this outpatient study, together with the higher risk shown in a previous study on hospitalised patients, suggests a causal relationship. This is of importance since bronchopneumonia seems highly linked to fatal outcome. In the absence of a mechanism, further investigation of the role of antipsychotics in older people is needed. PMID:20883613

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

    Directory of Open Access Journals (Sweden)

    Swartz Marvin

    2006-02-01

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

  1. Dosage and duration of antipsychotic treatment in demented outpatients with agitation or psychosis.

    Science.gov (United States)

    Lin, Yi-Ting; Hwang, Tzung-Jeng; Shan, Jia-Chi; Chiang, Huey-Ling; Sheu, Yi-Han; Hwu, Hai-Gwo

    2015-02-01

    The USA Food and Drug Administration (FDA) issued warnings regarding the use of antipsychotics in patients with dementia in 2003 and 2005. We aimed to study the dose and duration of antipsychotic treatment in dementia, and to examine whether physicians' prescription behaviors changed after the FDA warnings. Medical charts of outpatients who had Alzheimer's disease, vascular dementia, or mixed dementia were reviewed. Patients must have achieved a clinically stable state for at least 4 weeks after receiving antipsychotic treatment for agitation or psychosis. Demographics, clinical correlates, and duration of antipsychotic treatment were compared among different antipsychotic groups. Because the quetiapine group had the largest sample size, the optimal dose and duration of quetiapine treatment were compared among three time periods (before 2003, 2003-2005, after 2005). Stable state was achieved in 215 patients (80 had Alzheimer's disease, 117 vascular dementia, and 18 mixed dementia). Most patients (177) took quetiapine, 25 took risperidone, and 13 took sulpiride. The whole sample had a long total duration of antipsychotic treatment (median 525 days, mean 707 days). The median dose and total duration of antipsychotic treatment were 1.0mg/day and 238 days for risperidone, 100mg/day and 390 days for sulpiride, and 25mg/day and 611 days for quetiapine, respectively. The optimal dose and total duration of quetiapine treatment decreased significantly after FDA warning in 2005, although the duration remained long. The optimal doses of antipsychotics were not higher than those of western reports, but the total duration of antipsychotic treatment was quite long. Although our study suggests the prescription dosage and duration of antipsychotic treatment decreased significantly after FDA warning in 2005, the duration of treatment was still long. Given the serious safety concerns, more effort should be made to avoid unnecessary and prolonged prescription. Copyright © 2012

  2. 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.

  3. 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.

  4. The therapeutic relationship and adherence to antipsychotic medication in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rosemarie McCabe

    Full Text Available OBJECTIVE: Previous research has shown that a better therapeutic relationship (TR predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia. METHODS: 134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity. RESULTS: Patient and clinician ratings of the TR were weakly inter-correlated (r(s = 0.13, p = 0.004, but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%. After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%. CONCLUSIONS: A better TR is associated with better adherence to medication among patients with schizophrenia. Patients' and clinicians' perspectives of the TR are both important, but may reflect distinct aspects.

  5. Hypothermia due to Antipsychotic Medication: A Systematic Review

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    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.

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

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

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

  7. Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

    DEFF Research Database (Denmark)

    Sahlberg, Marie; Holm, Ellen; Gislason, Gunnar H

    2015-01-01

    events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. METHODS AND RESULTS: We followed all treatment-naïve Danish citizens...

  8. Vitamin E for antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

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

    2018-01-17

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

  9. Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment.

    Science.gov (United States)

    Farahani, Arusha; Correll, Christoph U

    2012-04-01

    To perform a meta-analysis of antidepressant-antipsychotic cotreatment versus antidepressant or antipsychotic monotherapy for psychotic depression. We performed an electronic search (from inception of databases until February 28, 2011) in PubMed/MEDLINE, Cochrane Library, and PsycINFO, without language or time restrictions. Search terms were (psychosis OR psychotic OR hallucinations OR hallucinating OR delusions OR delusional) AND (depression OR depressed OR major depressive disorder) AND (random OR randomized OR randomly). Eight randomized, placebo-controlled acute-phase studies in adults (N = 762) with standardized criteria-defined psychotic depression (including Research Diagnostic Criteria, DSM-III, DSM-IV, or ICD-10) were meta-analyzed, yielding 10 comparisons. Antidepressant-antipsychotic cotreatment was compared in 5 trials with 6 treatment arms (n = 337) with antidepressant monotherapy and in 4 trials with 4 treatment arms (n = 447) with antipsychotic monotherapy. Primary outcome was study-defined inefficacy; secondary outcomes included all-cause discontinuation, specific psychopathology ratings, and side effects. Using random effects models, we calculated relative risk (RR) with 95% confidence intervals (CIs), number-needed-to-treat/harm (NNT/NNH), and effect size (ES). Antidepressant-antipsychotic cotreatment outperformed antidepressant monotherapy regarding less study-defined inefficacy (no. of comparisons = 6; n = 378; RR = 0.76; 95% CI, 0.59-0.98; P = .03; heterogeneity [I2] = 34%) (NNT = 7; 95% CI, 4-20; P = .009) and Clinical Global Impressions-Severity of Illness scores (no. of comparisons = 4; n = 289; ES = -0.25; 95% CI, -0.49 to -0.02; P = .03; I2 = 0%), with trend-level superiority for depression ratings (no. of comparisons = 5; n = 324; ES = -0.20; 95% CI, -0.44 to 0.03; P = .09; I2 = 10%), but not regarding psychosis ratings (no. of comparisons = 3; n = 161; ES = -0.24; 95% CI, -0.85 to 0.38; P = .45; I2 = 70%). Antidepressant-antipsychotic

  10. Antipsychotic Polypharmacy among Children and Young Adults in Office-Based or Hospital Outpatient Department Settings

    Directory of Open Access Journals (Sweden)

    Minji Sohn

    2017-11-01

    Full Text Available The purpose of the study was three-fold: (1 to estimate the national trends in antipsychotic (AP polypharmacy among 6- to 24-year-old patients in the U.S.; (2 to identify frequently used AP agents and mental disorder diagnoses related to AP polypharmacy; and (3 to assess the strength of association between AP polypharmacy and patient/provider characteristics. We used publicly available ambulatory health care datasets to evaluate AP polypharmacy in office-based or hospital outpatient department settings to conduct a cross-sectional study. First, national visit rates between 2007 and 2011 were estimated using sampling weights. Second, common diagnoses and drugs used in AP polypharmacy were identified. Third, a multivariate logistic regression model was developed to assess the strength of association between AP polypharmacy and patient and provider characteristics. Between 2007 and 2011, approximately 2% of office-based or hospital outpatient department visits made by 6- to 24-year-old patients included one or more AP prescriptions. Of these visits, 5% were classified as AP polypharmacy. The most common combination of AP polypharmacy was to use two or more second-generation APs. Also, bipolar disorder and schizophrenia were the two most frequent primary mental disorder diagnoses among AP polypharmacy visits. The factors associated with AP polypharmacy were: older age (young adults, black, having one or more non-AP prescriptions, and having schizophrenia or ADHD.

  11. Patient and Health Care Provider Perspectives on Long Acting Injectable Antipsychotics in Schizophrenia and the Introduction of Olanzapine Long-Acting Injection

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    Heidi J. Wehring

    2011-01-01

    Full Text Available Olanzapine long acting injection has joined risperidone and paliperidone as the second generation long acting antipsychotic injection options for treatment of patients with schizophrenia. Long acting injections are important alternatives to oral medications for patients who have difficulty adhering to daily or multiple daily medication administrations, yet may be underutilized or not well understood. Patient perceptions, adherence, and preferences are important issues for health care providers to address when discussing treatment options with their patients. Reviewed here are overall patient and health care provider attitudes and perceptions regarding long acting injections and the details of olanzapine long acting injectable, the newest agent, and how it will fit in the marketplace. In addition, efficacy, safety, dosing and use data regarding this newest long acting agent are reviewed and compared to other available long acting agents.

  12. What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.

    Science.gov (United States)

    Wykes, T; Evans, J; Paton, C; Barnes, T R E; Taylor, D; Bentall, R; Dalton, B; Ruffell, T; Rose, D; Vitoratou, S

    2017-10-01

    Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

  13. Antipsychotic polypharmacy and quality of life in patients with schizophrenia treated in primary care in China.

    Science.gov (United States)

    Hou, Cai-Lan; Ma, Xin-Rong; Zang, Yu; Jia, Fu-Jun; Lin, Yong-Qiang; Chiu, Helen F K; Ungvari, Gabor S; Ng, Chee H; Zhong, Bao-Liang; Cao, Xiao-Lan; Li, Yan; Cai, Mei-Ying; Xiang, Yu-Tao

    2016-01-01

    In China, maintenance treatment for clinically stable patients with schizophrenia is usually provided by primary care physicians, but their prescribing patterns have not been studied. This study examined the frequency as well as demographic and clinical correlates of antipsychotic polypharmacy (APP) and its impact on quality of life (QOL) in patients with schizophrenia treated in primary care in China. A total of 623 community-dwelling patients from 18 randomly selected primary care services were interviewed. Patients' socio-demographic and clinical characteristics, including number of hospitalizations, antipsychotic drug-induced side effects, and QOL were recorded using a standardized protocol and data collection procedure. The rate of APP prescription was 31% (193/623). Of the patients on APP, 89.6% received 2 antipsychotics, 10.4% received 3 or more antipsychotics. Clozapine (35.6%) was the most commonly prescribed second generation antipsychotic (SGA), while perphenazine (17.8%) was the most commonly prescribed first generation antipsychotic (FGA). Multiple logistic regression analyses revealed that patients on APP were more likely to receive SGAs and anticholinergics, had fewer hospitalizations, younger age of onset, and higher doses of antipsychotics. There were no significant differences between the two groups in any of the QOL domains. Approximately a third of Chinese patients with schizophrenia in primary care receive APP. Further examination of the rationale and appropriateness of APP and its alternatives is warranted.

  14. 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.

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

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    Ludovic Samalin

    2016-11-01

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

  16. 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

  17. Does a history of suicide attempt predict higher antipsychotic dosage in schizophrenia?

    Science.gov (United States)

    Hettige, Nuwan C; Kennedy, James L; De Luca, Vincenzo

    2014-06-01

    Antipsychotic dosage is generally adjusted by physicians depending on the stability of the patient and the response to that particular drug. Our hypothesis is that patients with previous suicide attempt are prescribed higher doses of antipsychotics. We examined the dosage and patterns of antipsychotic use in regard to past suicidal behaviour. For this study, 304 subjects with schizophrenia spectrum disorders between the ages of 18 and 75 were recruited. A cross-sectional assessment was used for this study, in which data were collected from each patient through an interview and self-report questionnaires. The percentages of the Compendium of Pharmaceuticals and Specialties (CPS) maximum recommended daily dose were applied to standardize antipsychotic dosages across different treatments. We compared the standardized dosage of antipsychotics in schizophrenics with previous suicide attempts and those who have never attempted suicide. Applying the ANCOVA, our preliminary results show no significant difference (P = 0.467) in antipsychotic dosage in the attempters and non-attempters. The prescribed clozapine dosage fails to show a significant relationship with suicidal history (P >0.05). In summary, our analysis does not show antipsychotic dosage adjustment based on past suicide attempt, after controlling for the current suicidal ideation and hopelessness.

  18. Survey of antipsychotic medication curriculum content in Australian university nursing programmes.

    Science.gov (United States)

    Morrison, Paul; Stomski, Norman J; McAllister, Margaret; Wynaden, Dianne; Hungerford, Catherine; Usher, Kim; Maude, Phil; Crowther, Andrew; Batterbee, Robert

    2017-02-01

    Antipsychotic medication has long been one of the first-line interventions for people with serious mental illness, with outcomes including reductions in symptoms and relapse rates. More recently, however, questions have been raised about the efficacy of antipsychotic medications, especially in light of their side-effect profile. Such questions have implications for the nurses administering antipsychotic medications, particularly in relation to their knowledge of the antipsychotic medication, its efficacy, and side-effect profile. Also important is the education of nursing students about antipsychotic medications, their use, and management. The present study reports findings of research that explored current curriculum content concerning psychopharmacological treatment in Australian undergraduate and postgraduate nursing programmes. Using a survey design, the research examined the content and modes of delivery of this content to gauge how well students are prepared for administering antipsychotic medication to people with serious mental illness. Findings of the research suggested the need for improvement in preparing nursing students to administer antipsychotic medication, including indications, contraindications, as well as recognition and management of side-effects. © 2016 Australian College of Mental Health Nurses Inc.

  19. The STRIDE weight loss and lifestyle intervention for individuals taking antipsychotic medications: a randomized trial.

    Science.gov (United States)

    Green, Carla A; Yarborough, Bobbi Jo H; Leo, Michael C; Yarborough, Micah T; Stumbo, Scott P; Janoff, Shannon L; Perrin, Nancy A; Nichols, Greg A; Stevens, Victor J

    2015-01-01

    The STRIDE study assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism. The study design was a multisite, parallel two-arm randomized controlled trial in community settings and an integrated health plan. Participants who met inclusion criteria were ≥18 years old, were taking antipsychotic agents for ≥30 days, and had a body mass index ≥27. Exclusions were significant cognitive impairment, pregnancy/breastfeeding, recent psychiatric hospitalization, bariatric surgery, cancer, heart attack, or stroke. The intervention emphasized moderate caloric reduction, the DASH (Dietary Approaches to Stop Hypertension) diet, and physical activity. Blinded staff collected data at baseline, 6 months, and 12 months. Participants (men, N=56; women, N=144; mean age=47.2 years [SD=10.6]) were randomly assigned to usual care (N=96) or a 6-month weekly group intervention plus six monthly maintenance sessions (N=104). A total of 181 participants (90.5%) completed 6-month assessments, and 170 (85%) completed 12-month assessments, without differential attrition. Participants attended 14.5 of 24 sessions over 6 months. Intent-to-treat analyses revealed that intervention participants lost 4.4 kg more than control participants from baseline to 6 months (95% CI=-6.96 kg to -1.78 kg) and 2.6 kg more than control participants from baseline to 12 months (95% CI=-5.14 kg to -0.07 kg). At 12 months, fasting glucose levels in the control group had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in the intervention group from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study-related; medical hospitalizations were reduced in the intervention group (6.7%) compared with the control group (18.8%). Individuals taking antipsychotic medications can lose

  20. Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: overview of systematic reviews

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    Tamara Melnik

    Full Text Available CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS is 20-40%. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline (1966-2009, Controlled Trials of the Cochrane Collaboration (2009, Issue 2, Embase (Excerpta Medica (1980-2009, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs (1982-2009. There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

  1. Use of antipsychotic and antidepressant within the Psychiatric Disease Centre, Regional Health Service of Ferrara.

    Science.gov (United States)

    Bianchi, Stefano; Bianchini, Erica; Scanavacca, Paola

    2011-12-20

    This study aimed at describing the type and dosage of psychopharmaceuticals dispensed to patients with psychiatric disorders and to assess the percentage of patients treated with antipsychotics and antidepressants, the associated therapies, treatment adherence, and dosages used in individuals registered at the Psychiatric Disease Center (PDC), Regional Health Service of Ferrara. The analysis focused on therapeutic programmes presented to the Department of Pharmacy of the University Hospital of Ferrara of 892 patients treated by the PDC (catchment area of 134605 inhabitants). All diagnoses were made according to International Classification of Diseases (ICD-9). The analysis focused on prescriptions from September 2007 to June 2009. Data on adherence to prescribed therapy have were processed by analysis of variance. Among the patients 63% were treated with antipsychotics and 40% with antidepressants. Among patients receiving antipsychotics 92% used second-generation antipsychotics (SGAs) whereas the remaining 8% used first generation antipsychotics (FGAs). Antipsychotic doses were lower than Daily Defined Dose (DDDs), and SGAs were often given with anticholinergics to decrease side effects. Mean adherence to antipsychotic therapy was 64%. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were the most often prescribed, 55%. Dosages of these were within the limits indicated by the technical datasheet but higher than DDDs. Only 26% of patients underwent monotherapy. In antidepressants polytherapy, medication was associated with another antidepressant, 6% or with an antipsychotic, 51%. Mean adherence to the antidepressant therapy was 64%. Patients treated with antipsychotics tend to use doses lower than DDDs. The opposite tendency was noted in patients treated with antidepressants. Only a small percentage of patients (14%) modified their neuroleptic therapy by increasing the dosage. On the contrary, patients treated with antidepressants mainly

  2. Postprandial prolactin suppression appears absent in antipsychotic-treated male patients.

    Science.gov (United States)

    Coello, Klara; Broberg, Brian V; Bak, Nikolaj; Madsen, Anna; Mortensen, Henrik B; Søgaard, Birgitte; Szecsi, Pal B; Knop, Filip K; Lublin, Henrik; Ebdrup, Bjørn H

    2015-10-01

    Hyperprolactinemia is a common side-effect of antipsychotic treatment. Antipsychotics and hyperprolactinemia are both considered risk factors of metabolic disturbances and diabetes. Investigations on prolactin response to meal ingestion in antipsychotic-treated patients are missing. In a case-control design, 49 antipsychotic-treated, clinically stable, non-diabetic, schizophrenia spectrum male patients were compared with 93 healthy male controls by age (33.1, SD 7.4 vs. 32.9, SD 6.6 years), body mass index (26.2, SD 4.6 vs. 26.1, SD 3.9 kg/m(2)) and waist circumference (96.4, SD 13.0 vs. 96.7, SD 11.9 cm). Serum-prolactin was measured in the morning and 90 min after ingestion of a standardized liquid meal (2268 kJ). Fasting prolactin levels varied considerably, and mean fasting prolactin levels did not significantly differ between patients and controls (12.33, SD 11.58 vs. 10.06, SD 8.67 ng/ml, p = 0.623). In the controls, postprandial serum prolactin was significantly reduced (Δ -2.53, SD 9.75 ng/ml, p = 0.016). In antipsychotic-treated patients postprandial serum prolactin tended to increase (Δ 2.62, SD 10.96 ng/ml, p = 0.081). Analyses of subgroups based on the prolactinogenic liability of their antipsychotic treatment indicated 22 to 65% higher postprandial prolactin levels with high and intermediate prolactinogenic antipsychotics. A physiological postprandial suppression of serum prolactin appears absent in antipsychotic-treated males. Marked variability in fasting prolactin levels may reflect individual variations in the diurnal cycle. Uniform acquisition procedures accounting for diurnal variation and food intake may enhance reliability of prolactin levels in antipsychotic-treated male patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    Starace, Fabrizio; Mungai, Francesco; Barbui, Corrado

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wen-Yin Chen

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

  5. 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.

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

    Science.gov (United States)

    Forray, Carlos; Buller, Raimund

    2017-11-01

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

  7. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies

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    Haddad PM

    2014-06-01

    Full Text Available Peter M Haddad,1,2 Cecilia Brain,3,4 Jan Scott5,6 1Neuroscience and Psychiatry Unit, University of Manchester, Manchester, 2Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK; 3Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, 4Nå Ut-teamet, Psychosis Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Academic Psychiatry, Institute of Neuroscience, Newcastle University, 6Centre for Affective Disorders, Institute of Psychiatry, London, UK Abstract: Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders

  8. A comparison of electronic monitoring vs. clinician rating of antipsychotic adherence in outpatients with schizophrenia.

    Science.gov (United States)

    Byerly, Matthew; Fisher, Robert; Whatley, Katrina; Holland, Rhiannon; Varghese, Femina; Carmody, Thomas; Magouirk, Brianne; Rush, A John

    2005-02-28

    Antipsychotic non-adherence rates of outpatients with schizophrenia or schizoaffective disorder was assessed by electronic monitoring and clinician rating. Antipsychotic adherence was determined monthly over 3 consecutive months with (1) the Medication Event Monitoring System (MEMS) cap and (2) the Clinician Rating Scale. Non-adherence was defined as daily adherence of <70% during any one of three monthly evaluations for MEMS and ratings of antipsychotic non-adherence.

  9. 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...

  10. Antipsychotic Polypharmacy in Children and Adolescents at Discharge from Psychiatric Hospitalization

    Science.gov (United States)

    Saldaña, Shannon N.; Keeshin, Brooks R.; Wehry, Anna M.; Blom, Thomas; Sorter, Michael T.; DelBello, Melissa P.; Strawn, Jeffrey R.

    2014-01-01

    Study Objective Antipsychotic polypharmacy—the use of more than one second-generation antipsychotic—has increased in children and adolescents and may be associated with increased adverse effects, nonadherence, and greater costs. Thus, we sought to examine the demographic and clinical characteristics of psychiatrically hospitalized children and adolescents who were prescribed antipsychotic polypharmacy and to identify predictors of this prescribing pattern. Design Retrospective medical record review. Setting Large, acute care, urban, children's hospital, inpatient psychiatric unit. Patients One thousand four hundred twenty-seven children and adolescents who were consecutively admitted and discharged between September 2010 and May 2011. Measurements and Main Results At discharge, 840 (58.9%) of the 1427 patients were prescribed one or more antipsychotics, 99.3% of whom received second-generation antipsychotics. Of these 840 patients, 724 (86.2%) were treated with antipsychotic monotherapy, and 116 (13.8%) were treated with antipsychotic polypharmacy. Positive correlations with antipsychotic polypharmacy were observed for placement or custody outside the biological family; a greater number of previous psychiatric admissions; longer hospitalizations; admission for violence/aggression or psychosis; and intellectual disability, psychotic, disruptive behavior, or developmental disorder diagnoses. Negative correlations with antipsychotic polypharmacy included admission for suicidal ideation/attempt or depression, and mood disorder diagnoses. Significant predictors of antipsychotic polypharmacy included admission for violence or aggression (odds ratio [OR] 2.76 [95% confidence interval (CI) 1.36-5.61]), greater number of previous admissions (OR 1.21 [95% CI 1.10-1.33]), and longer hospitalizations (OR 1.08 [95% CI 1.04-1.12]). In addition, diagnoses of intellectual disability (OR 2.62 [95% CI 1.52-4.52]), psychotic disorders (OR 5.60 [95% CI 2.29-13.68]), and

  11. 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 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 raloxifene in

  12. Risk of discontinuation of antipsychotic long-acting injections vs. oral antipsychotics in real-life prescribing practice: a community-based study.

    Science.gov (United States)

    Verdoux, H; Pambrun, E; Tournier, M; Bezin, J; Pariente, A

    2017-05-01

    To compare the risk of discontinuation of ambulatory antipsychotic treatment in persons treated with antipsychotic long-acting injections (LAIs) or by oral antipsychotics (OAPs). The study was performed in a representative sample of persons newly treated with OAPs (n = 6904) affiliated to the French Insurance Healthcare system. The risk of all-cause discontinuation was compared in patients prescribed OAPs (n = 246) vs. matched patients prescribed LAIs (n = 246) using multivariate survival analyses. Confounding by indication was minimized by matching on type of antipsychotic drug and by the high-dimensional propensity score method. Discontinuation was more frequent with OAPs (69%) compared to LAIs (57%) [adjusted relative risk (aRR) = 1.6, 95% CI 1.23-2.07]. Risk of discontinuation was higher for first-generation (FGA) OAPs vs. FGA LAIs (aRR = 1.94, 95% CI 1.22-3.08) as well as for second-generation (SGA) OAPs vs. SGA LAIs (aRR = 1.58, 95% CI 1.15-2.17). Over the 6-month period after discontinuation of LAIs, a new antipsychotic drug was dispensed in 58% of patients, the most frequent pattern being dispensing of the same LAI as that prescribed before discontinuation. Although less frequent than with OAPs, the rate of ambulatory treatment discontinuation was high with LAIs. Prescription of LAIs should be associated with intervention strategies aimed at promoting medication adherence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Importance of intervention timing in the effectiveness of antipsychotics.

    Science.gov (United States)

    Liu, Yia-Ping; Yang, Yu-Yin; Wan, Fang-Jung; Tung, Che-Se

    2018-02-02

    The use of early pharmacological intervention in treating young patients with schizophrenia is a debating issue for psychiatrists. However, on the basis of developmental theory, early antipsychotic intervention can be beneficial in terms of protecting neurons from further deterioration. This study investigated whether the initiation of second-generation antipsychotic (SGA) treatment at a younger age can effectively reverse schizophrenia-relevant behavioral and neurochemical features, namely acoustic prepulse inhibition (PPI) and accumbal dopamine (DA) efflux, respectively. Risperidone (RIS, 1mg/kg/day) or olanzapine (OLA, 2.5mg/kg/day) was administered for 6weeks in rats subjected to isolation rearing (IR) in adolescence or young adulthood. Behavioral testing was performed at 3 and 5 (for locomotor activity) and 2 and 4 (for PPI) weeks after the initiation of the pharmacological regimen. An additional PPI test was performed 6weeks after the initiation of the pharmacological regimen to assess the acute add-on effect of RIS or OLA. Dopamine (DA) efflux of the nucleus accumbens was evaluated through in vivo microdialysis at the end of the study, for measuring both the baseline levels after the chronic regimen and the responsiveness to acute add-on RIS or OLA treatment. Our results demonstrated that the effects of SGAs on PPI and accumbal DA efflux were dissociated. Specifically, RIS intervention was more beneficial for adolescent than young adult IR rats in restoring their PPI deficit, whereas OLA was age-independently effective in stimulating the accumbal DA efflux. Both PPI and accumbal DA could be employed to reflect IR-induced abnormalities, in which accumbal DA appeared to be more suitable in depicting the long-term effect of IR, whereas PPI might be a more accurate biological index for revealing the advantages of early RIS intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

  15. Geographical variation in antipsychotic drug use in elderly patients with dementia

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    A delicate balance exists between the central dopaminergic and cholinergic neurotransmitter systems with respect to motor function. An imbalance can result in motor dysfunction as observed in Parkinson's disease patients and in patients treated with antipsychotic compounds. Cholinergic receptor...... antagonists can alleviate extrapyramidal symptoms in Parkinson's disease and motor side effects induced by antipsychotics. The effects of anticholinergics are mediated by muscarinic receptors of which five subtypes (M1–M5) exist. Muscarinic M4 receptors are found at high concentrations in motor parts...... of the striatum, suggesting a role for muscarinic M4 receptors in the motor side effects of antipsychotics, and in the alleviation of these side effects by anticholinergics. Here we investigated the potential role of the muscarinic M4 receptor in catalepsy induced by antipsychotics (haloperidol and risperidone...

  18. The atypical anti-psychotic clozapine decreases bone mass in rats in vivo.

    Science.gov (United States)

    Costa, Jessica L; Smith, Greg; Watson, Maureen; Lin, Jian-Ming; Callon, Karen; Gamble, Greg; Cheng, Anthony; Vickers, Mark H; Shepherd, Peter R; Cornish, Jillian; Grey, Andrew

    2011-03-01

    Fracture risk is increased in patients with schizophrenia, who often receive long-term therapy with anti-psychotic drugs. The mechanisms by which skeletal fragility is increased in patients with psychosis include increased risk of falling, but direct skeletal toxicity of anti-psychotic drugs is a possibility that has not been investigated. We examined the skeletal effects, in vivo and in vitro, of a typical anti-psychotic drug, haloperidol, which primarily inhibits dopaminergic signaling, and an atypical anti-psychotic drug, clozapine, which predominantly inhibits serotonergic signaling. In growing rats, 42 days of clozapine treatment reduced whole body bone mineral density by 15% (Pactions to reduce osteoblast growth and function. Long-term administration of clozapine may therefore negatively affect bone health, and clinical studies to investigate this possibility are warranted. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Does a GLP-1 receptor agonist change glucose tolerance in patients treated with antipsychotic medications?

    DEFF Research Database (Denmark)

    Larsen, Julie Rask; Vedtofte, Louise; Holst, Jens Juul

    2014-01-01

    BACKGROUND: Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances. Addition......BACKGROUND: Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances...... treatment with either clozapine or olanzapine. Outcomes: The primary endpoint is the change in glucose tolerance from baseline (measured by area under the curve for the plasma glucose excursion following a 4 h 75 g oral glucose tolerance test) to follow-up at week 16. The secondary endpoints include changes...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  3. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk

    DEFF Research Database (Denmark)

    Borg, Linda; Julkunen, Anna; Madsen, Kristian Rørbaek

    2016-01-01

    It is often advised that patients who have ingested an overdose of antidepressants (AD) or antipsychotics (AP) are monitored with continuous ECG for minimum of 12-24 hr. These patients are often observed in an ICU. Our aim was to identify the number of patients with AD and/or AP overdose without...... adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need...... as antipsychotic overdose who would not require initial intensive care treatment. This is the first time the ADORA system has been evaluated in patients with antidepressant as well as antipsychotic overdose. This article is protected by copyright. All rights reserved....

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss......Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern...... of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  6. 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

  7. 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

  8. 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...

  9. Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study.

    Science.gov (United States)

    Hatta, Kotaro; Kishi, Yasuhiro; Wada, Ken; Odawara, Toshinari; Takeuchi, Takashi; Shiganami, Takafumi; Tsuchida, Kazuo; Oshima, Yoshio; Uchimura, Naohisa; Akaho, Rie; Watanabe, Akira; Taira, Toshihiro; Nishimura, Katsuji; Hashimoto, Naoko; Usui, Chie; Nakamura, Hiroyuki

    2014-03-01

    Attention to risk of antipsychotics for older patients with delirium has been paid. A clinical question was whether risk of antipsychotics for older patients with delirium would exceed efficacy of those even in the general hospital setting. A prospective observational study proceeded over a 1-year period at 33 general hospitals, where at least one psychiatrist worked full time. Subjects were patients who developed delirium during their admission due to acute somatic diseases or surgery, and who received antipsychotics for delirium. The primary outcome was rates and kinds of serious adverse events. Among 2834 patients who developed delirium, 2453 patients received antipsychotics, such as risperidone (34%), quetiapine (32%), and parenteral haloperidol (20%), for delirium. Out of 2453 patients, 22 serious adverse events (0.9%) were reported. Aspiration pneumonia was the most frequent (17 patients, 0.7%), followed by cardiovascular events (4 patients, 0.2%) and venous thromboembolism (1 patient, 0.0%). There was no patient with a fracture or intracranial injury due to a fall. No one died because of antipsychotic side effects. The mean Clinical Global Impressions-Improvement Scale score was 2.02 (SD 1.09). Delirium was resolved within 1 week in more than half of the patients (54%). In the general hospital setting under management including fine dosage adjustment and early detection of side effects, risk of antipsychotics for older patients with delirium might be low, in contrast to antipsychotics for dementia in the nursing home or outpatient settings. A point may be not how to avoid using antipsychotics but how to monitor their risk. © 2013 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

  10. "The Lesser of Two Evils" Versus "Medicines not Smarties": Constructing Antipsychotics in Dementia.

    Science.gov (United States)

    Gill, Dilbagh; Almutairi, Saleh; Donyai, Parastou

    2017-11-21

    Because antipsychotics are associated with an increased risk of morbidity and mortality, they should only be prescribed in dementia in limited circumstances. But antipsychotics are prescribed to a large proportion of residents in formal care settings despite guidance and warnings to the contrary, justifying a study into how professionals define and in turn create realities about antipsychotic usage in dementia. Twenty-eight professionals with a role in the care and management of patients with dementia in care homes were recruited and interviewed in this qualitative study. A gap in the literature about the social construction of antipsychotics in dementia prompted the use of critical discourse analysis methodology. Antipsychotics were portrayed in 2 distinct ways; as "the lesser of two evils' they were conceptualized as the less harmful or unpleasant of 2 bad choices and as "medicines not Smarties" (a brand of sweets/candy) they were conceptualized as prescribed too frequently and indiscriminately. The first resource could be used to defend the prescribing of antipsychotics and uphold the prescribers' privilege to do so whereas the second enabled the speaker to reject their own wilful involvement in overprescribing. When prescribers draw on "the lesser of two evils" paradigm to sanction the overprescribing of antipsychotics, implicit assumptions about these medications as being the best of bad choices should be recognized and challenged. Future studies should target specific normative beliefs about antipsychotic prescribing consequences, to change the lexicon of common knowledge which perpetuates bad practice. © The Author 2017. 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.

  11. Combined treatment with atypical antipsychotics and antidepressants in treatment-resistant depression: preclinical and clinical efficacy.

    Science.gov (United States)

    Rogóż, Zofia

    2013-01-01

    Several clinical reports have documented a beneficial effect of adding atypical antipsychotic drugs to ongoing treatments with antidepressants, particularly selective serotonin reuptake inhibitors, in ameliorating drug-resistant depression. The aim of this paper was to summarize some preclinical evidence describing the mechanism responsible for the therapeutic action of combined treatment with antidepressants and atypical antipsychotics and also some clinical data supporting the efficacy and safety of the augmentation strategy for improving antidepressant-resistant depression using atypical antipsychotics. This analysis is based on five microdialysis studies and nine behavioral studies assessing the impact of combined atypical antipsychotic and antidepressant treatments on extracellular levels of dopamine, serotonin and noradrenaline in the prefrontal cortex of freely moving rats and on antidepressant-induced effects, respectively. In addition, clinical data demonstrating the efficacy and safety of augmentation strategies for treatment-resistant depression using atypical antipsychotics were included. Combined treatment of rats with all studied atypical antipsychotics (olanzapine, risperidone, clozapine and quetiapine) and antidepressants (citalopram, fluoxetine and fluvoxamine) increased the extracellular level of dopamine in the prefrontal cortex compared to a respective drug given alone; in addition, a combination of olanzapine or quetiapine plus fluoxetine or fluvoxamine increased the levels of dopamine and noradrenaline. Moreover, atypical antipsychotics administered in a low dose enhanced the antidepressant-like activity of antidepressants, with (among other mechanisms) the serotonin 5-HT1A, 5-HT2A and adrenergic α2 receptors likely playing an important role in their action. The results support the conclusion that atypical antipsychotics may be effective as adjunctive therapy in treatment-resistant depression; however, their adverse effect profile may be

  12. Attitudes toward antipsychotic treatment among patients with bipolar disorders and their clinicians: a systematic review

    Directory of Open Access Journals (Sweden)

    Sajatovic M

    2017-08-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Brandl EJ

    2011-08-01

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

  15. Comparative Effectiveness of Second-Generation Antipsychotic Medications in Early-Onset Schizophrenia

    Science.gov (United States)

    Olfson, Mark; Gerhard, Tobias; Huang, Cecilia; Lieberman, Jeffrey A.; Bobo, William V.; Crystal, Stephen

    2012-01-01

    Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001–2005) was analyzed focusing on outpatients, aged 6–17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ2 = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ2 = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57–1.61) for olanzapine, 1.03 (95% CI: 0.59–1.81) for quetiapine, 0.85 (95% CI: 0.43–1.70) for aripiprazole, and 1.22 (95% CI: 0.60–2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome

  16. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging

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    Howes, OD; Egerton, A; Allan, V; McGuire, P; Stokes, P; Kapur, S

    2009-01-01

    Molecular imaging studies have generated important in vivo insights into the etiology of schizophrenia and treatment response. This article first reviews the PET and SPECT evidence implicating dopaminergic dysfunction, especially presynaptic dysregulation, as a mechanism for psychosis. Second, it summarises the neurochemical imaging studies of antipsychotic action, focussing on D2/3 receptors. These studies show that all currently licensed antipsychotic drugs block striatal D2/3 receptors in ...

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

    Directory of Open Access Journals (Sweden)

    Ricardo Alberto Moreno

    2004-10-01

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

  18. Antipsychotic medication and remission of psychotic symptoms 10years after a first-episode psychosis.

    Science.gov (United States)

    Wils, Regitze Sølling; Gotfredsen, Ditte Resendal; Hjorthøj, Carsten; Austin, Stephen F; Albert, Nikolai; Secher, Rikke Gry; Thorup, Anne Amalie Elgaard; Mors, Ole; Nordentoft, Merete

    2017-04-01

    Several national guidelines recommend continuous use of antipsychotic medication after a psychotic episode in order to minimize the risk of relapse. However some studies have identified a subgroup of patients who obtain remission of psychotic symptoms while not being on antipsychotic medication for a period of time. This study investigated the long-term outcome and characteristics of patients in remission of psychotic symptoms with no use of antipsychotic medication at the 10-year follow-up. The study was a cohort study including 496 patients diagnosed with schizophrenia spectrum disorders (ICD 10: F20 and F22-29). Patients were included in the Danish OPUS Trial and followed up 10years after inclusion, where patient data was collected on socio-demographic factors, psychopathology, level of functioning and medication. 61% of the patients from the original cohort attended the 10-year follow up and 30% of these had remission of psychotic symptoms at the time of the 10-year follow up with no current use of antipsychotic medication. This outcome was associated with female gender, high GAF-F score, participation in the labour market and absence of substance abuse. Our results describe a subgroup of patients who obtained remission while not being on antipsychotic medication at the 10-year follow-up. The finding calls for further investigation on a more individualized approach to long-term treatment with antipsychotic medication. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Natasha S Kate

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-11-30

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

  2. Antipsychotic Drug Effects in Schizophrenia: A Review of Longitudinal fMRI Investigations and Neural Interpretations

    Science.gov (United States)

    Abbott, C.C.; Jaramillo, A.; Wilcox, C.E.; Hamilton, D.A.

    2013-01-01

    The evidence that antipsychotics improve brain function and reduce symptoms in schizophrenia is unmistakable, but how antipsychotics change brain function is poorly understood, especially within neuronal systems. In this review, we investigated the hypothesized normalization of the functional magnetic resonance imaging (fMRI) blood oxygen level dependent signal in the context of antipsychotic treatment. First, we conducted a systematic PubMed search to identify eight fMRI investigations that met the following inclusion criteria: case-control, longitudinal design; pre- and post-treatment contrasts with a healthy comparison group; and antipsychotic-free or antipsychotic-naïve patients with schizophrenia at the start of the investigation. We hypothesized that aberrant activation patterns or connectivity between patients with schizophrenia and healthy comparisons at the first imaging assessment would no longer be apparent or “normalize” at the second imaging assessment. The included studies differed by analysis method and fMRI task but demonstrated normalization of fMRI activation or connectivity during the treatment interval. Second, we reviewed putative mechanisms from animal studies that support normalization of the BOLD signal in schizophrenia. We provided several neuronal-based interpretations of these changes of the BOLD signal that may be attributable to long-term antipsychotic administration. PMID:23157635

  3. Antipsychotic utilization in the intensive care unit and in transitions of care.

    Science.gov (United States)

    Marshall, John; Herzig, Shoshana J; Howell, Michael D; Le, Stephen H; Mathew, Chris; Kats, Julia S; Stevens, Jennifer P

    2016-06-01

    The objective of this study was to quantify the rate at which newly initiated antipsychotic therapy is continued on discharge from the intensive care unit (ICU) and describe risk factors for continuation post-ICU discharge. This is a retrospective cohort study of all patients receiving an antipsychotic in the ICUs of a large academic medical center from January 1, 2005, to October 31, 2011. Medical record review was conducted to ascertain whether a patient was newly started on antipsychotic therapy and whether therapy was continued post-ICU discharge. A total of 39,248 ICU admissions over the 7-year period were evaluated. Of these, 4468 (11%) were exposed to antipsychotic therapy, of which 3119 (8%) were newly initiated. In the newly initiated cohort, 642 (21%) were continued on therapy on discharge from the hospital. Type of drug (use of quetiapine vs no use of quetiapine: odds ratio, 3.2; 95% confidence interval, 2.5-4.0; P antipsychotics on discharge despite adjustment for clinical factors. Antipsychotic use is common in the ICU setting, and a significant number of newly initiated patients have therapy continued upon discharge from the hospital. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-06-01

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

  5. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Directory of Open Access Journals (Sweden)

    Boonlue T

    2016-04-01

    Full Text Available Tuanthon Boonlue,1,2 Suphat Subongkot,1,2 Piyameth Dilokthornsakul,3,4 Ronnachai Kongsakon,5 Oraluck Pattanaprateep,6 Orabhorn Suanchang,7 Nathorn Chaiyakunapruk3,8–10 1Clinical Pharmacy Division, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand; 2The College of Pharmacotherapy of Thailand, Nonthaburi, Thailand; 3Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 4Center for Pharmaceutical Outcomes Research, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA; 5Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Department of Health Informatics, Ramathibodi Hospital, Mahidol University, 7Department of Pharmacy, Somdet Chaopraya Institute of Psychiatry, Bangkok, Thailand; 8School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 9School of Population Health, University of Queensland, Brisbane, Australia; 10School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA Background: Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective: This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods: From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual

  6. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  7. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    Directory of Open Access Journals (Sweden)

    JP Lindenmayer

    2010-05-01

    Full Text Available JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

  8. Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

    Science.gov (United States)

    Schirmbeck, Frederike; Mier, Daniela; Esslinger, Christine; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

    2015-01-01

    Background Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations The main limitation of this study is its cross-sectional design. Conclusion To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations. PMID:25268790

  9. 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.

  10. Treatment of Young People With Antipsychotic Medications in the United States.

    Science.gov (United States)

    Olfson, Mark; King, Marissa; Schoenbaum, Michael

    2015-09-01

    Despite concerns about rising treatment of young people with antipsychotic medications, little is known about trends and patterns of their use in the United States. To describe antipsychotic prescription patterns among young people in the United States, focusing on age and sex. A retrospective descriptive analysis of antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 (n = 765,829), 2008 (n = 858,216), and 2010 (n = 851,874), including a subset from calendar year 2009 with service claims data (n = 53,896). Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. The percentage of young people filling 1 or more antipsychotic prescriptions during the study year by sex and age group (younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years) was calculated. Among young people with antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined. The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%). Approximately 29.3% of

  11. Deficient striatal adaptation in aminergic and glutamatergic neurotransmission is associated with tardive dyskinesia in non-human primates exposed to antipsychotic drugs.

    Science.gov (United States)

    Lévesque, Catherine; Hernandez, Giovanni; Mahmoudi, Souha; Calon, Frédéric; Gasparini, Fabrizio; Gomez-Mancilla, Baltazar; Blanchet, Pierre J; Lévesque, Daniel

    2017-10-11

    Tardive dyskinesia (TD) is a potentially disabling condition encompassing all delayed, persistent, and often irreversible abnormal involuntary movements arising in a fraction of subjects during long-term exposure to centrally acting dopamine receptor-blocking agents such as antipsychotic drugs and metoclopramide. However, the pathogenesis of TD has proved complex and remains elusive. To investigate the mechanism underlying the development of TD, we have chronically exposed 17 Cebus apella monkeys to typical (11) or atypical (6) antipsychotic drugs. Six additional monkeys were used as controls. Using autoradiography, Western blot and in situ hybridization techniques, we compared neurochemical components of the dopamine, serotonin, and glutamate neurotransmitter systems modulating striatal activity in monkeys chronically exposed to haloperidol and clozapine. Five (5) out of 11 monkeys treated with haloperidol develop TD, whereas none of the monkeys treated with clozapine develop TD. Haloperidol treatment significantly upregulated the levels of serotonin 5-HT 2A receptor, NR2A-containing NMDA receptors, and tyrosine hydroxylase contents in the monkey putamen, whereas clozapine regulated putamen NMDA receptor levels and tyrosine hydroxylase contents, and 5-HT 2A and dopamine transporter outside the putamen. Comparisons of neurochemical alterations between dyskinetic and non dyskinetic animals within the haloperidol-treated group indicate that modulations of 5-HT 2A , metabotropic glutamate type 5, NR2A- and NR2B-containing NMDA receptors, and vesicular monoamine transporter type 2 levels were restricted to the non dyskinetic group. The foregoing results suggest that TD is associated with complex deficient adaptation in aminergic and glutamatergic neurotransmission in the striatum of non-human primates chronically exposed to antipsychotic drugs. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. [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.

  13. Comparative safety of atypical antipsychotics and the risk of pneumonia in the elderly.

    Science.gov (United States)

    Mehta, Sandhya; Pulungan, Zulkarnain; Jones, Barton T; Teigland, Christie

    2015-12-01

    Previous studies have documented increased risk of pneumonia with antipsychotic use in the elderly; however, differential risk across individual atypical antipsychotics remains unaddressed. This study examines the effect of individual atypical antipsychotics on risk of pneumonia in elderly patients. This retrospective cohort study was conducted using a large claims database. The study population included new users of atypical antipsychotics (≥65 years). The multiple propensity-score adjusted survival model was used to examine risk of pneumonia within a 1-year follow-up period. A total of 92 234 patients newly prescribed atypical antipsychotic medication were identified. Of these, 41 780 (45.30%) were quetiapine users, 31 048 (33.66%) risperidone users, 11 375 (12.33%) olanzapine users, 6790 (7.36%) aripiprazole users, and 1241 (1.35%) ziprasidone users. Within the 1-year follow-up period, 12 411 (13.46%) patients taking atypical antipsychotics had a diagnosis of pneumonia. The multiple propensity-score-adjusted survival model revealed increased risk of pneumonia with the use of risperidone (hazard ratios (HR) 1.14, 95%CI 1.10-1.18) and olanzapine (HR 1.10, 95%CI 1.04-1.16) compared with the use of quetiapine. This large population-based study suggests that use of risperidone and olanzapine increases risk of pneumonia compared with use of quetiapine in elderly patients. This study provides new information on the comparative risk of pneumonia associated with different atypical antipsychotics in the elderly to support optimal treatment decisions. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Budman, Cathy L

    2014-07-01

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

  15. Cocaine use in individuals with schizophrenia: impact on doses of discharge antipsychotic medications.

    Science.gov (United States)

    Mohite, Satyajit; Ngana, Ikenna; Okusaga, Olaoluwa O

    2015-01-01

    Despite the high prevalence of cocaine use disorder in schizophrenia, the impact of cocaine on antipsychotic requirement has not been studied in this population. The aim of this study was to evaluate the effect of cocaine on doses of antipsychotic medication prescribed during periods of acute exacerbation of psychotic symptoms in individuals with schizophrenia. We reviewed the medical records of individuals with schizophrenia discharged from hospitals between 2008 and 2012. Student t tests and linear regression were used to compare doses of discharge antipsychotic medications (in chlorpromazine equivalents) between individuals with schizophrenia with cocaine positive urine drug test results (n = 180; age 42.71 ± 10.03 years) and individuals with schizophrenia with negative urine drug test results (n = 3194; age 38.49 ± 12.86 years). Unadjusted analysis revealed that individuals with schizophrenia who tested positive for cocaine were discharged on lower doses of antipsychotic medication compared with those who tested negative (449.88 ± 2.12 vs 515.47 ± 2.16; P = 0.021). However, after adjusting for age, sex, race, and length of stay, the 2 groups did not differ on doses of discharge antipsychotic medication (geometric mean difference 7.41; CI: 7.62-12.30; P = 0.703). Our preliminary result suggests that cocaine use does not impact significantly on the doses of antipsychotic medication prescribed during periods of acute exacerbation of psychosis in schizophrenia and individuals with schizophrenia with comorbid cocaine use disorder may require similar doses of antipsychotic medication as those without cocaine use disorder.

  16. Adherence to antipsychotic medication among homeless adults in Vancouver, Canada: a 15-year retrospective cohort study.

    Science.gov (United States)

    Rezansoff, Stefanie N; Moniruzzaman, A; Fazel, S; Procyshyn, R; Somers, J M

    2016-12-01

    The purpose of this study was to investigate the level of adherence to antipsychotic prescription medication in a well-defined homeless cohort over a 15-year period. We hypothesized that adherence would be well below the recommended threshold for clinical effectiveness (80 %), and that it would be strongly associated with modifiable risk factors in the social environment in which homeless people live. Linked baseline data (including comprehensive population-level administrative prescription records) were examined in a subpopulation of participants from two pragmatic-randomized trials that investigated Housing First for homeless and mentally ill adults. Adherence to antipsychotic medication was operationalized using the medication possession ratio. Multivariable logistic regression was used to estimate effect sizes between socio-demographic, homelessness-related and illness factors, and medication possession ratio. Among the 290 participants who met inclusion criteria for the current analysis, adherence to antipsychotic prescription was significantly associated with: history of psychiatric hospitalization; receipt of primary medical services; long-acting injectable antipsychotic formulations; and duration of homelessness. Mean medication possession ratio in the pre-randomization period was 0.41. Socio-demographic characteristics previously correlated with antipsychotic non-adherence were not significantly related to medication possession ratio. This is the first study to quantify the very low level of adherence to antipsychotic medication among homeless people over an extended observation period of 15 years. Each of the four factors found to be significantly associated with adherence presents opportunities for intervention. Strategies to end homelessness for this population may represent the greatest opportunity to improve adherence to antipsychotic medication.

  17. Antipsychotic drugs rapidly induce dopamine neuron depolarization block in a developmental rat model of schizophrenia.

    Science.gov (United States)

    Valenti, Ornella; Cifelli, Pierangelo; Gill, Kathryn M; Grace, Anthony A

    2011-08-24

    Repeated administration of antipsychotic drugs to normal rats has been shown to induce a state of dopamine neuron inactivation known as depolarization block, which correlates with the ability of the drugs to exhibit antipsychotic efficacy and extrapyramidal side effects in schizophrenia patients. Nonetheless, in normal rats depolarization block requires weeks of antipsychotic drug administration, whereas schizophrenia patients exhibit initial effects soon after initiating antipsychotic drug treatment. We now report that, in a developmental disruption rat model of schizophrenia [methyl-azoxymethanol acetate (20 mg/kg, i.p.) injected into G17 pregnant female rats, with offspring tested as adults], the extant hyperdopaminergic state combines with the excitatory actions of a first- (haloperidol; 0.6 mg/kg, i.p.) and a second- (sertindole; 2.5 mg/kg, i.p.) generation antipsychotic drug to rapidly induce depolarization block in ventral tegmental area dopamine neurons. Acute injection of either antipsychotic drug induced an immediate reduction in the number of spontaneously active dopamine neurons (cells per electrode track; termed population activity). Repeated administration of either antipsychotic drug for 1, 3, 7, 15, and 21 d continued to reduce dopamine neuron population activity. Both acute and repeated effects on population activity were reversed by acute apomorphine injections, which is consistent with the reversal of dopamine neuron depolarization block. Although this action may account for the effects of D2 antagonist drugs on alleviating psychosis and the lack of development of tolerance in humans, the drugs appear to do so by inducing an offsetting deficit rather than attacking the primary pathology present in schizophrenia.

  18. Is paliperidone palmitate more effective than other long-acting injectable antipsychotics?

    Science.gov (United States)

    Patel, R; Chesney, E; Taylor, M; Taylor, D; McGuire, P

    2017-10-17

    Paliperidone palmitate is one of the most widely prescribed long-acting injectable (LAI) antipsychotics in the UK. However, it is relatively expensive and there are few data comparing its effectiveness to that of other LAI antipsychotics. We sought to address this issue by analyzing a large anonymized electronic health record (EHR) dataset from patients treated with LAI antipsychotics. EHR data were obtained from 1281 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who started treatment with a LAI antipsychotic between 1 April 2011 and 31 January 2015. The number of days spent as a psychiatric inpatient and the number of admissions to a psychiatric hospital were analyzed in each of the 3 years before and after LAI prescription. Patients treated with paliperidone palmitate (n = 430; 33.6%) had a greater number of inpatient days and a greater number of admissions in the year prior to treatment than those treated with other LAI antipsychotics. Nevertheless, in the 3 years after initiation there were no significant differences between paliperidone and the other LAI antipsychotics in the number of days as an inpatient (B coefficient 5.4 days, 95% confidence interval (CI) -57.3 to 68.2, p = 0.86) or number of hospital admissions (Incidence rate ratio 1.07, 95% CI 0.62 to 1.83, p = 0.82). Paliperidone palmitate was more likely to be prescribed in patients with more frequent and lengthy hospital admissions prior to initiation. However, the absence of differences in outcomes after initiation indicates that paliperidone palmitate was not more effective than other cheaper LAI antipsychotics.

  19. Posttraumatic Stress Disorder, Antipsychotic Use and Risk of Dementia in Veterans.

    Science.gov (United States)

    Roughead, Elizabeth E; Pratt, Nicole L; Kalisch Ellett, Lisa M; Ramsay, Emmae N; Barratt, John D; Morris, Philip; Killer, Graeme

    2017-07-01

    To examine the risk of dementia associated with posttraumatic stress disorder (PTSD) and the contribution of antipsychotic use to this risk. Retrospective cohort study SETTING: Australia. Administrative claims data from the Australian Government Department of Veterans' Affairs were used. Male Vietnam veterans aged 55 to 65 at baseline (2001-02) with no preexisting dementia diagnosis (N = 15,612). The association between PTSD and dementia was assessed over 12 years of follow-up. Dementia was identified as a hospital diagnosis, dementia record in service disability data, or dispensing of medicines for dementia. Cox-proportional hazards models were used, with age as the time-scale. Results were stratified according to baseline antipsychotic use. No greater risk of dementia was observed with PTSD. In veterans who received antipsychotics, dementia risk was significantly higher than in those who did not (hazard ratio (HR) = 2.1, 95% confidence interval (CI) = 1.4-3.3). Dementia risk was significantly greater in veterans hospitalized for PTSD who received antipsychotics (HR = 2.2, 95% CI = 1.1-4.6) and veterans without PTSD who received antipsychotics (HR = 4.3, 95% CI = 2.1-8.6) than in those without PTSD with no antipsychotic use. Antipsychotic use may be a contributor to dementia risk. These findings should be interpreted with caution because the study design was observational. Further research using prospective study designs in settings where diagnostic data, cognitive function, and disease severity are available are required. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  20. Pharmacoepidemiology of Antipsychotic Use in Youth with ADHD: Trends and Clinical Implications

    Science.gov (United States)

    Birnbaum, Michael L.; Saito, Ema; Gerhard, Tobias; Winterstein, Almut; Olfson, Mark; Kane, John M.; Correll, Christoph U.

    2014-01-01

    Although concern has been raised about antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalences and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) antipsychotic-treated youth (N=15, n=341,586); 2) ADHD youth (N=9, n=6,192,368), and 3) general population youth (N=5, n=14,284,916). Altogether, 30.5±18.5% of antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998-2007) from 21.7±7.1% to 27.7±7.7%, ratio=1.3±0.4. Furthermore, 11.5±17.5% of ADHD youth received antipsychotics. In longitudinal studies, this percentage also increased (1998-2006) from 5.5±2.6% to 11.4±6.7%, ratio=2.1±0.6. Finally, 0.12±0.07% of youth in the general population were diagnosed with ADHD and received antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993-2007): 0.13±0.09% to 0.44±0.49%, ratio=3.1±2.2. Taken together, these data indicate that antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation. PMID:23881713

  1. Implications of atypical antipsychotic prescribing in the intensive care unit.

    Science.gov (United States)

    Kram, Bridgette L; Kram, Shawn J; Brooks, Kelli R

    2015-08-01

    The purpose of the study was to determine the downstream implications of atypical antipsychotic (AAP) prescribing in the intensive care unit (ICU), including discharge prescribing practices, monitoring, and attributable adverse drug events. This retrospective cohort study included patients at least 18 years of age admitted to an ICU that received at least 2 doses of an AAP for documented delirium or avoidance of a deliriogenic medication. Exclusion criteria were documentation of an AAP as a home medication or initiation for a psychiatric indication unrelated to delirium (eg, schizophrenia). During the 8-month study period, 156 patients were included and 133 (85.2%) patients survived to hospital discharge. Of the survivors, AAP therapy was continued for 112 (84.2%) patients upon ICU transfer and for 38 (28.6%) patients upon hospital discharge. A majority of these patients had evidence of delirium resolution or no indication for continuation documented at discharge. Of the 127 patients with an electrocardiogram ordered during AAP therapy, QTc prolongation occurred in 49 (31.4%) patients. An adverse drug event leading to drug discontinuation was documented in 16 (10.2%) patients. Because of significant patient-centered implications, AAPs initiated in the ICU require continued evaluation for indication to avoid prolonged and possibly unnecessary use. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    Zachary Freyberg

    2017-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Sonja Gandhi

    2016-04-01

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

  4. Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis

    Science.gov (United States)

    Zhang, Jian-Ping; Lencz, Todd; Zhang, Ryan X.; Nitta, Masahiro; Maayan, Lawrence; John, Majnu; Robinson, Delbert G.; Fleischhacker, W. Wolfgang; Kahn, Rene S.; Ophoff, Roel A.; Kane, John M.; Malhotra, Anil K.; Correll, Christoph U.

    2016-01-01

    Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2–20, n = 81–2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values antipsychotic exposure (pediatric or first episode patients) and short follow-up (1–2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic

  5. Adherence to Antipsychotic Medication and Criminal Recidivism in a Canadian Provincial Offender Population.

    Science.gov (United States)

    Rezansoff, Stefanie N; Moniruzzaman, Akm; Fazel, Seena; McCandless, Lawrence; Somers, Julian M

    2017-09-01

    Preliminary evidence suggests that adherence to antipsychotic medication reduces criminal recidivism among patients diagnosed with schizophrenia. However, existing studies operationalize antipsychotic adherence as a binary variable (usually using a threshold of ≥80%), which does not reflect the prevalence of suboptimal adherence in real-world settings. The purpose of the current analysis was to investigate the association between successive ordinal levels of antipsychotic adherence and criminal recidivism in a well-defined sample of offenders diagnosed with schizophrenia (n = 11462). Adherence was measured using the medication possession ratio (MPR) and analyzed as a time-dependent covariate in multivariable regression models. Data were drawn from linked, comprehensive diagnostic, pharmacy and justice system records, and individuals were followed for an average of 10 years. Adjusted rate ratios (ARR) and confidence intervals (CI) are reported. Overall mean MPR was 0.41. Increasing levels of antipsychotic adherence were not associated with progressively lower rates of offending. However, when compared to the reference group (MPR ≥ 80%) all lower adherence levels were significantly associated (P recidivism. Future research addressing functional outcomes of antipsychotic adherence should conceptualize adherence as an incremental independent variable. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  6. TEAR FILM ANALYSIS IN PATIENTS ON CHRONIC ANTI-PSYCHOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    B. Radhakrishnan

    2017-12-01

    Full Text Available BACKGROUND Dry eye disease is a well-known side effect of antipsychotic therapy which is often neglected due to nonspecific symptoms. Therefore, this study is to analyse tear film dysfunction in patients on chronic antipsychotic therapy. MATERIALS AND METHODS Study was undertaken on 200 eyes of 100 patients who were on chronic anti-psychotic therapy attending the Psychiatry OPD. Out of 100 patients, 65 patients were male, rest 35 were females. Ocular examination was done on all patients which included BCVa, slit lamp evaluation and dry eye evaluation. RESULTS 32 out of 100 patients on chronic anti-psychotic therapy had dry eye disease. 17 (53.13% out of these 32 patients had symptoms suggestive of dry eye disease. Patients on typical antipsychotics and multidrug regimen showed more prevalence of dry eye. CONCLUSION Nearly 40% patients were in Grade 3 category of dry eye disease, which if not treated on time can lead to further progression and complication of disease. Patients may not come out with symptoms of ocular diseases so it is mandatory to screen these patients to diagnose early and to prevent complications. This study emphasizes on the need to give importance to patients symptoms so that it can be detected earlier before it progresses.

  7. Foster care, externalizing disorders, and antipsychotic use among Medicaid-enrolled youths.

    Science.gov (United States)

    Vanderwerker, Lauren; Akincigil, Ayse; Olfson, Mark; Gerhard, Tobias; Neese-Todd, Sheree; Crystal, Stephen

    2014-10-01

    The authors investigated the extent to which clinical diagnoses of externalizing disorders explain higher rates of antipsychotic use by foster care youths. Medicaid claims data from 44 states for 2009 for youths in foster care (N=301,894) and those not in foster care (N=5,092,574) were analyzed, excluding those with schizophrenia, bipolar disorder, autism, and major depressive disorder. Logistic regressions assessed the relationship between foster care, externalizing disorders, and antipsychotic use. Foster care youths had higher rates of externalizing disorders than the comparison group (attention-deficit hyperactivity disorder, 17.3% versus 6.5%; disruptive behavior disorder, 7.2% versus 2.5%; conduct disorder, 2.3% versus .5%) and greater antipsychotic use (7.4% versus 1.4%). Foster care remained a significant predictor of antipsychotic use after control for demographic and diagnostic covariates, including externalizing disorders (adjusted odds ratio=2.59, 95% confidence interval=2.54-2.63). High rates of externalizing disorder diagnoses only partially explained elevated levels of antipsychotic use in this vulnerable population.

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

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    Williams Sylvain

    2006-03-01

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

  9. Long-Acting Injectable Antipsychotics for First-Episode Schizophrenia: The Pros and Cons

    Directory of Open Access Journals (Sweden)

    Borah Kim

    2012-01-01

    Full Text Available Clinical and psychosocial deterioration associated with schizophrenia occurs within the first few years following the onset of the illness. Therefore, to improve the long-term prognosis, it is important to provide schizophrenia patients with intensive treatment following their first episode. Relapse is highly associated with partial medication adherence or nonadherence in patients with first-episode schizophrenia. Recent studies suggest that long-acting injectable (LAI antipsychotics compared with oral antipsychotics are more effective for medication adherence and relapse prevention. Moreover, some clinical guidelines for the treatment of schizophrenia suggested that LAI antipsychotics should be considered when patients are nonadherent “at any stage.” Decreased compliance is a common cause of relapse during the initial stages of the disease. Therefore, LAI antipsychotics should be highly considered when treating patients with first-episode schizophrenia. In the present paper, clinical trial data and current guidelines on the use of LAI antipsychotics for first-episode schizophrenia are discussed as well as the pros and cons of this treatment option.

  10. The potential role of atypical antipsychotics in the treatment of panic disorder.

    Science.gov (United States)

    Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

    2014-09-01

    Many studies have investigated the efficacy and tolerability of alternative pharmacotherapy for panic disorder. This study aims to provide a comprehensive review of the existing literature regarding the efficacy and tolerability of atypical antipsychotics for panic disorder. We searched for relevant published articles using Medline, the Cochrane database, and EMBASE on 19 June 2013. Prospective studies that examined the efficacy and tolerability of atypical antipsychotics in the treatment of primary panic disorder or comorbid panic disorder (or symptoms) in other psychiatric disorders were included in this review. Seven prospective studies were included in this review. Among these, four were open-label studies for refractory panic disorder. Two of the seven included studies were randomized controlled trials among patients with panic symptoms comorbid with bipolar disorder. The remaining study was a randomized controlled trial for panic disorder or panic attack comorbid with major depression. Except one negative risperidone study, the reviewed studies showed the favorable efficacy results of atypical antipsychotics. Although the majority of the evidence regarding the efficacy of atypical antipsychotics in the treatment of panic disorder comes from small, open-label studies, this review suggests the potential role of atypical antipsychotics in treating panic disorder. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Reduction or discontinuation of antipsychotics for challenging behaviour in adults with intellectual disability: a systematic review.

    Science.gov (United States)

    Sheehan, Rory; Hassiotis, Angela

    2017-03-01

    The use of antipsychotics to manage challenging behaviour in adults with intellectual disability is widespread but controversial, and evidence is scarce. There is a perception that antipsychotics used in this context can be reduced or discontinued, and this has been a major focus of recent national policy. However, such an intervention risks harm as well as having potential benefits. We reviewed the available evidence and found that antipsychotics can be reduced or discontinued in a substantial proportion of adults who use them for challenging behaviour, although not always without adverse effects. There is a group which displays behavioural deterioration on antipsychotic reduction that prevents discontinuation; predictors of poor response could not be reliably identified. In view of the relatively scarce data and methodological limitations of the available studies, we cannot draw firm conclusions to inform a population level approach to this issue. Antipsychotic medication used for behaviour should be reviewed regularly and an individualised approach taken to treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment.

    Science.gov (United States)

    Zetterberg, Henrik; Jakobsson, Joel; Redsäter, Mikael; Andreasson, Ulf; Pålsson, Erik; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette Gm; Blennow, Kaj; Landén, Mikael

    2014-07-30

    Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Rapid Growth Of Antipsychotic Prescriptions For Children Who Are Publicly Insured Has Ceased, But Concerns Remain.

    Science.gov (United States)

    Crystal, Stephen; Mackie, Thomas; Fenton, Miriam C; Amin, Shahla; Neese-Todd, Sheree; Olfson, Mark; Bilder, Scott

    2016-06-01

    The rapid growth of antipsychotic medication use among publicly insured children in the early and mid-2000s spurred new state efforts to monitor and improve prescription behavior. A starting point for many oversight initiatives was the foster care system, where most of the children are insured publicly through Medicaid. To understand the context and the effects of these initiatives, we analyzed patterns and trends in antipsychotic treatment of Medicaid-insured children in foster care and those in Medicaid but not in foster care. We found that the trend of rapidly increasing use of antipsychotics appears to have ceased since 2008. Children in foster care treated with antipsychotic medications are now more likely than other Medicaid-insured children to receive psychosocial interventions and metabolic monitoring for the side effects of the medications. However, challenges persist in increasing safety monitoring and access to psychosocial treatment. Development of specialized managed care plans for children in foster care represents a promising policy opportunity. New national quality measures for safe and judicious antipsychotic medication use are also now available to guide improvement. Oversight policies developed for foster care appear to have potential for adaptation to the broader population of Medicaid-covered children. Project HOPE—The People-to-People Health Foundation, Inc.

  14. 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

    OpenAIRE

    Selva-Vera, Gabriel; Balanza-Martinez, Vicent; Salazar-Fraile, José; Sánchez-Moreno, José; Martínez-Arán, Anabel, 1971-; Correa, Patricia; Vieta i Pascual, Eduard, 1963-; Tabarés-Seisdedos, Rafael

    2010-01-01

    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 performa...

  15. 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.

  16. Effectiveness and risks of combining antipsychotic drugs with electroconvulsive treatment.

    Science.gov (United States)

    Sanz-Fuentenebro, Francisco Javier; Vidal Navarro, Ignacio; Ballesteros Sanz, Daniel; Verdura Vizcaíno, Ernesto

    2011-01-01

    The simultaneous application of electroconvulsive therapy (ECT) and psychotropic drugs is based on sparse data. Despite this, and the restrictive approach of the Guidelines and Consensus is widespread in the usual care, it is widely practiced in routine clinical. We reviewed the results of search on the topic in MEDLINE, PsychINFO, EMBASE and Cochrane, and the main guidelines on the subject and analyzed for drug groups. Except some reservation with regard to classical MAOIs, antidepressants are safe and effective enhancers of the TEC. It is desirable to discontinuation of BZD whenever clinically possible before the course of ECT for risk of interference, if not possible will have to use proper technique to ensure effective incentives. It is advisable to stop or reduce the dose of lithium prior to ECT based on a cost-benefit analysis of the risk of relapse, if maintained will be adjusted lower levels and cognitive effects minimizing techniques. The combination with "classic" and "atypical" antipsychotics power positive clinical effects and the risk of combined use is low. The positive data are collected with clozapine and ECT-resistant psychosis, with little presence of effects of the decrease of seizure threshold by clozapine, and important effect of empowerment, but of limited duration. Although it is strictly necessary to identify situations in terms of drugs, patient and ECT technique, and care necessary to develop tests that provide methodologically sound data, the combined use of ECT and psychotropic drugs in general presents an acceptable risk level and efficacy data by encouraging empowerment. Copyright © 2010 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  17. How Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment.

    Science.gov (United States)

    Rubio-Abadal, Elena; Del Cacho, Núria; Saenz-Navarrete, Gerard; Arranz, Belen; Cambra, Rosa-Maria; Cuadras, Daniel; Rodante, Demián; Fehér, Csaba; Roca, Mercedes; Barneda, Vanessa; Usall, Judith

    2016-10-01

    We aimed to study the relationship between hyperprolactinemia (HPRL) and sexual dysfunction (SED) in a sample of patients being prescribed a dose-stable antipsychotic medication, and to evaluate sex differences in the prevalence of HPRL and SED and their relationship. A cross-sectional study was carried out including patients between 18 and 55 years of age with a psychotic spectrum diagnosis who were attending community mental health services or hospitalized in medium and long stay units. Positive and Negative Syndrome scale, Calgary depression scale for schizophrenia, Personal and Social Performance scale, and Changes in Sexual Functioning questionnaire-short form were administered. Not later than 3 months, a determination of prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen (only in women) and testosterone was performed. A final sample of 101 patients (30 women and 71 men) was recruited. Seventy-two patients (71.3%) showed HPRL. Sexual dysfunction was significantly higher in HPRL patients than in non-HPRL patients (79.17% vs 51.72%) (P = 0.006), and mean prolactin values were significantly higher in case of SED (P = 0.020). No sex differences were found in prevalence of HPRL or SED. Low Personal and Social Performance scale scores and HPRL were factors independently associated with SED, whereas alcohol use was an independent protector factor. In our study, SED was significantly related to HPRL without showing sex differences. Prevalence of HPRL and SED observed was higher than that in previous studies, which should be taken into consideration because these have been associated with higher morbimortality, and noncompliance and relapse, respectively.

  18. Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter; Lublin, H

    2010-01-01

    OBJECTIVE: To evaluate the effect of a multifaceted educational intervention on the frequency of antipsychotic co-prescribing in adult schizophrenia out-patients. METHOD: Controlled quasi-experimental study performed in two Danish municipalities matched for baseline prevalence of antipsychotic po...

  19. Age, Race, and Gender Differences in Antipsychotic Medication Use among Children Prior to Entry to Out-of-Home Care

    Science.gov (United States)

    Robst, John; Armstrong, Mary; Dollard, Norin

    2009-01-01

    There is growing literature examining the use of psychotropic medications and specifically antipsychotic medications among youth in the United States. This study uses administrative claims data to assess antipsychotic medication use among children prior to being served in therapeutic out-of-home care settings and whether there are utilization…

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  1. Probabilistic classification and gambling in patients with schizophrenia receiving medication: comparison of risperidone, olanzapine, clozapine and typical antipsychotics.

    Science.gov (United States)

    Wasserman, James I; Barry, Rebecca J; Bradford, Lisa; Delva, Nicholas J; Beninger, Richard J

    2012-07-01

    We have previously shown that patients with schizophrenia treated with typical antipsychotics were impaired on the weather prediction probabilistic classification learning (PCL) task that relies on striatal function, and that similar patients treated with atypical antipsychotics were impaired on the Iowa gambling task (IGT) that depends on medial prefrontocortical function. We tested the hypothesis that test performance of patients treated with risperidone will be more similar to those treated with typical rather than atypical antipsychotics. Groups of schizophrenia patients treated with risperidone, olanzapine, clozapine or typical antipsychotics did not differ on the Positive and Negative Syndrome Scale or the Mini Mental State Exam (MMSE) but scored lower than controls on the MMSE. For the PCL task, patients treated with clozapine improved over trials while those treated with typical antipsychotics, olanzapine, or risperidone did not. For the IGT, patients treated with typical antipsychotics or risperidone improved over trials while those treated with clozapine or olanzapine did not. Results generally supported the hypothesis that patients treated with risperidone perform more like those treated with typical antipsychotics than those treated with other atypical antipsychotics.

  2. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study.

    NARCIS (Netherlands)

    Mulder, H.; Franke, B.; Beek, A.A. van der; Arends, J.; Wilmink, F.W.; Egberts, A.C.G.; Scheffer, H.

    2007-01-01

    The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were

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

    Science.gov (United States)

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

    2010-01-01

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

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Thomas J Reilly

    2017-03-01

    Full Text Available Objectives: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. Methods: We present a case report of a patient who developed this syndrome with various sequelae. Results: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. Conclusions: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

  6. Cognitive behaviour therapy in patients with schizophrenia who are not prescribed antipsychotic medication: a case series.

    Science.gov (United States)

    Christodoulides, T; Dudley, R; Brown, S; Turkington, D; Beck, Aaron T

    2008-06-01

    Cognitive behaviour therapy (CBT) as an adjunct to medication has been shown to improve symptom management in patients with schizophrenia. However, little is understood about the value of CBT for people who are not prescribed antipsychotic medication. A post hoc case series design was used to examine the outcome data of three participants selected from a randomized controlled trial for CBT for schizophrenia. The participants were included if they had received CBT and were not prescribed antipsychotic medication during active treatment. The three patients improved on outcome measures of psychopathology, depression, or negative symptoms, some to a clinically significant degree. CBT is a feasible treatment for people with schizophrenia who are not prescribed antipsychotic medication. It may be a valuable alternative to medication in treating symptoms of schizophrenia.

  7. Beliefs about antipsychotic versus hypoglycemic medications among individuals with serious mental illness and type 2 diabetes.

    Science.gov (United States)

    Aakre, Jennifer M; Medoff, Deborah R; Dixon, Lisa B; Kreyenbuhl, Julie A

    2012-01-01

    This study compared the beliefs held by individuals with coexisting serious mental illness and type 2 diabetes regarding the necessity and risks of taking antipsychotic versus hypoglycemic medications. We also investigated whether nonadherent patients differed from adherent patients in their beliefs about medications. Forty-four individuals with type 2 diabetes and serious mental illness who were prescribed hypoglycemic and antipsychotic medications completed a cross-sectional assessment of medication beliefs and adherence for both medication types. Patients perceived a greater need for hypoglycemic versus antipsychotic medications; however, their beliefs were not associated with nonadherence to either medication type. These results suggest that individuals with coexisting serious mental illness and type 2 diabetes have stronger convictions regarding the necessity of their diabetes medication for maintaining their health.

  8. Antipsychotic drugs cause bradycardia in GD 13 rat embryos in vitro.

    Science.gov (United States)

    Gunnström, M; Ababneh, D; Webster, W S; Oakes, D; Ritchie, H

    2012-11-01

    This study investigated the effects of antipsychotic drugs on heart function of gestational day (GD) 13 rat embryos in vitro since they all block the I(Kr)/hERG potassium ion channel in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested antipsychotic drugs caused bradycardia of the rat embryonic heart in a concentration-dependent manner. However, with the possible exception of haloperidol the tested drugs did not cause arrhythmias typically seen with the highly selective I(Kr)/hERG blocking drug dofetilide. For six of the eight drugs tested the effects on the embryonic rat heart were only seen at free drug concentrations that were much greater than those likely to occur in pregnant women taking antipsychotic medication. However, the safety margins for haloperidol and quetiapine were lower. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  9. 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...

  10. Global Micro- and Macro-structural White Matter Alterations and the reward circuit in First-episode Antipsychotic-naïve Schizophrenia Patients. Preliminary Results

    DEFF Research Database (Denmark)

    Raghava, Jayachandra Mitta; Ebdrup, Bjørn Hylsebeck; Nielsen, Mette Ødegaard

    to what extend WM alterations are present before and after the initiation of antipsychotic medication with amisulpride in anti-psychotic naïve schizophrenia patients. Methods Thirty-eight first-episode, antipsychotic-naive schizophrenia patients and 38 matched healthy controls were scanned on Philips 3T...

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

    Science.gov (United States)

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

    2015-07-01

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

  12. The US Food and Drug Administration's Perspective on the New Antipsychotic Pimavanserin.

    Science.gov (United States)

    Mathis, Mitchell V; Muoio, Brendan M; Andreason, Paul; Avila, Amy M; Farchione, Tiffany; Atrakchi, Aisar; Temple, Robert J

    2017-06-01

    To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. We describe the regulatory and clinical issues important to the FDA's approval of this New Drug Application, with special focus on the risk-benefit balance. We also describe a new labeling feature that presents additional efficacy data to clinicians. Data sets for all relevant clinical trials of pimavanserin and the Applicant's and FDA's analyses of these data were considered in this review. Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population. Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease. In the Applicant's single pivotal trial, 80.5% of pimavanserin patients experienced at least some improvement in symptoms compared to 58.1% of patients taking placebo. Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding. Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. Although pimavanserin appears to have a pharmacologic mechanism that is different from other atypical antipsychotics, concern remained that the increased risk of death seen with antipsychotic use in elderly demented patients, and described in all approved antipsychotic labels, would also occur with pimavanserin. Pimavanserin bears the same boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia. © Copyright 2017 Physicians Postgraduate Press, Inc.

  13. Hippocampal subregion volume changes associated with antipsychotic treatment in first-episode psychosis.

    Science.gov (United States)

    Rhindress, K; Robinson, D G; Gallego, J A; Wellington, R; Malhotra, A K; Szeszko, P R

    2017-07-01

    Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1-3, posterior CA1-3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability. Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans. This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

  14. Post-Stroke Mortality, Stroke Severity, and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study

    DEFF Research Database (Denmark)

    Prior, Anders; Laursen, Thomas Munk; Larsen, Karen Kjær

    2014-01-01

    Background and Purpose: It has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use. Methods: We conducted a nationwide......, population-based cohort study of 81,143 persons admitted with stroke in Denmark from 2003–2010. Using Danish health care databases, we extracted data on preadmission use of antipsychotics and confounding factors. We examined the association between current, former, and never use of antipsychotics and stroke...... severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching. Results: Current users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users...

  15. Changes in antipsychotic use among patients with severe mental illness after a Food and Drug Administration advisory.

    Science.gov (United States)

    Dusetzina, Stacie B; Busch, Alisa B; Conti, Rena M; Donohue, Julie M; Alexander, G Caleb; Huskamp, Haiden A

    2012-12-01

    A 2003 Food and Drug Administration advisory warned of increased hyperlipidemia and diabetes risk for patients taking second-generation antipsychotics (SGAs). After the advisory, a professional society consensus statement provided treatment recommendations and stratified SGAs into high, intermediate, and low metabolic risk. We examine subsequent changes in incident and prevalent SGA use among individuals with severe mental illness. We created a retrospective cohort using Florida Medicaid's claims from 2001 to 2006. We included non-Medicare eligible adults with bipolar disorder or schizophrenia who filled an SGA prescription. We assessed changes in overall and agent-specific use, discontinuations, interruptions, and therapeutic alternative use among prevalent users and agent-specific use among incident users. Pre-advisory utilization was compared with utilization initially after the advisory and two subsequent periods. Among prevalent users, overall SGA use decreased slightly, and no increases in treatment interruptions or discontinuations were observed after the advisory and consensus statement publication. Compared with the pre-advisory period, in the months immediately after the advisory, the use of the highest metabolic-risk agent, olanzapine, decreased by 34% among prevalent users with bipolar disorder (adjusted risk ratio [aRR] = 0.66, 95%CI = 0.59-0.74) and 26% among prevalent users with schizophrenia (aRR = 0.74, 95%CI = 0.72-0.76). A greater decrease was estimated among incident users with bipolar disorder (aRR = 0.37, 95%CI = 0.29-0.47) and schizophrenia (aRR = 0.42, 95%CI = 0.35-0.51) during this period. During each subsequent post-advisory period, olanzapine use continued to decrease whereas quetiapine, ziprasidone, and aripiprazole use increased. The metabolic risk advisory and the published consensus statement were associated with a selective reduction in olanzapine use without evidence of treatment disruptions among

  16. Metabolic syndrome in patients with severe mental illness undergoing psychiatric rehabilitation receiving high dose antipsychotic medication.

    Science.gov (United States)

    Ravindranath, Bapu V

    2012-07-01

    To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens. Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III) (NCEP ATP III) criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose. Out of 24 patients, 10 patients (41.7%) were receiving high dose antipsychotics (HDA) and four were on maximum dosage limits of 100%. 8.3% (2/24) patients were receiving only one first generation antipsychotics (FGA), 37.5% (9/24) patients were receiving only one second generation antipsychotic (SGA), 45.8% patients (11/24) were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN ("as needed") therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%). Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20) had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11) were on HDA and 27.3% (3/11) were on maximum British National Formulary (BNF) limits of 100% of dosage. Four out

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

    Science.gov (United States)

    Reeves, Gloria M; Keeton, Courtney; Correll, Christoph U; Johnson, Jacqueline L; Hamer, Robert M; Sikich, Linmarie; Hazzard, Lindsey; Alderman, Cheryl; Scheer, Abigail; Mabe, Micah; Kapoor, Sandeep; Sheridan, Eva; Borner, Irmgard; Bussell, Kristin; Pirmohamed, Sara; Bethea, Terrence C; Chekuri, Raja; Gottfried, Rhoda; Reinblatt, Shauna P; Santana, Erin; Riddle, Mark A

    2013-08-15

    Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8-19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to

  18. 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...

  19. Antipsychotic prescribing for behavioral disorders in US youth: physician specialty, insurance coverage, and complex regimens.

    Science.gov (United States)

    Burcu, Mehmet; Safer, Daniel J; Zito, Julie M

    2016-01-01

    To assess antipsychotic prescribing patterns according to insurance coverage type and physician specialty in the outpatient treatment of behavioral disorders (BD) in US youth. We used 2003-2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data to compare antipsychotic prescribing in the outpatient treatment of BD in youth (6-19 years) according to insurance coverage (public vs. private) and physician specialty (psychiatrist vs. non-psychiatrist) using population-weighted Chi-square and multivariable analyses. Also, we examined co-prescribing of antipsychotics with other psychotropic medication classes. Subgroup analyses were conducted in BD visits with no other clinician-reported psychiatric diagnosis (non-comorbid BD visits). A large majority (71.0%) of BD visits were provided by non-psychiatrists. However, psychiatrists prescribed antipsychotics far more frequently than non-psychiatrists (24.2% vs. 4.6%; adjusted odds ratio (AOR) = 5.1 [95% confidence interval (CI), 2.8-9.2]) in total BD visits as well as in non-comorbid BD visits (18.6% vs. 3.6%; AOR = 5.8 [95% CI, 3.2-10.5]). Antipsychotic prescribing was nearly two-fold greater in visits by publicly insured 6-12 year olds (11.3% vs. 5.8%; AOR = 1.9 [95% CI, 1.1-3.5]) and 13-19 year olds (16.2% vs. 8.9%; AOR = 2.0 [95% CI, 1.1-3.6]) compared with their privately insured counterparts. In more than one-third of antipsychotic-prescribed BD visits, antipsychotics were prescribed concomitantly with ≥2 psychotropic medication classes regardless of age group, insurance coverage, or even in the absence of psychiatric comorbidities. In outpatient visits by youth for BD, antipsychotics were primarily prescribed by psychiatrists, concomitantly, and for the publicly insured. These treatment patterns merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd.

  20. 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

  1. Synthesis and sar study of 2-substituted imidazo[2,1-b] [1,3]benzothiazoles and related compounds endowed with affinity for dopamine D2 receptors as potential antipsychotics

    OpenAIRE

    Asproni, Battistina; Kehler, Jan; Simula, Sergio; Mura, Stefania; Porcu, Giovanna

    2008-01-01

    Typical antipsychotic agents such as chlorpromazine and haloperidol block the D2 subtype of dopamine receptors in a direct relation to their clinical potency. In this context we have developed a series of (1,2-diphenyl-imidazolyl)piperazine derivatives (1) that are endowed with substantial affinities for both dopamine D2 receptors as well as 5-HT1A and 5-HT2A serotonin receptors, compound 1a (R = o-OCH3) of which is representative. We have extended our study on other series of compou...

  2. Quantification of selected antidepressants and antipsychotics in clinical samples using chromatographic methods combined with mass spectrometry: A review (2006-2015).

    Science.gov (United States)

    Sistik, Pavel; Turjap, Miroslav; Iordache, Andreea Maria; Saldanha, Helena M E B; Lemr, Karel; Bednar, Petr

    2016-03-01

    Psychiatric disorders contribute significantly to worldwide morbidity and mortality. In the case of depression and schizophrenia, effective drug therapy is available but 30-50% of patients do not respond sufficiently to the initial treatment regimen. Apart from the development of new molecules, it is desirable to optimize treatment outcomes with agents that are currently available. Therapeutic drug monitoring (TDM) is a suitable and widely accepted approach for improving the efficacy and safety of these drugs. A review of the relevant literature published between 2006 and January 2015. This review describes major advances and drawbacks in the field of chromatography coupled with single or tandem mass spectrometry (LC-MS, LC-MS/MS and GC/MS) of selected antidepressants (agomelatine, vilazodone) and antipsychotics (iloperidone, asenapine, amisulpride, aripiprazole, melperone, zotepine, ziprasidone). The high specificity in combination with high sensitivity makes these techniques an attractive complementary method to traditional procedures used in routine practice for TDM.

  3. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  4. A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia.

    Science.gov (United States)

    Nasrallah, Henry A; Gopal, Srihari; Gassmann-Mayer, Cristiana; Quiroz, Jorge A; Lim, Pilar; Eerdekens, Mariëlle; Yuen, Eric; Hough, David

    2010-09-01

    Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., ppaliperidone palmitate (5-6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.

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

    Directory of Open Access Journals (Sweden)

    Feng Mei

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

  6. The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder

    NARCIS (Netherlands)

    Abramovic, Lucija; Boks, Marco P M; Vreeker, Annabel; Bouter, Diandra C.; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H.; Ophoff, Roel A.; Kahn, René S.; van Haren, Neeltje E M

    2016-01-01

    There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain

  7. Postprandial prolactin suppression appears absent in antipsychotic-treated male patients

    DEFF Research Database (Denmark)

    Coello, Klara; Broberg, Brian V; Bak, Nikolaj

    2015-01-01

    INTRODUCTION: Hyperprolactinemia is a common side-effect of antipsychotic treatment. Antipsychotics and hyperprolactinemia are both considered risk factors of metabolic disturbances and diabetes. Investigations on prolactin response to meal ingestion in antipsychotic-treated patients are missing...... circumference (96.4, SD 13.0 vs. 96.7, SD 11.9 cm). Serum-prolactin was measured in the morning and 90 min after ingestion of a standardized liquid meal (2268 kJ). RESULTS: Fasting prolactin levels varied considerably, and mean fasting prolactin levels did not significantly differ between patients and controls...... (12.33, SD 11.58 vs. 10.06, SD 8.67 ng/ml, p = 0.623). In the controls, postprandial serum prolactin was significantly reduced (Δ -2.53, SD 9.75 ng/ml, p = 0.016). In antipsychotic-treated patients postprandial serum prolactin tended to increase (Δ 2.62, SD 10.96 ng/ml, p = 0.081). Analyses...

  8. 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 (pprolactin 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.

  9. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

    NARCIS (Netherlands)

    Knegtering, Henderikus; van den Bosch, Rob; Castelein, Stynke; Bruggeman, Richard; Sytema, Sjoerd; van Os, Jim

    Objective: To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. Method: A large sample (n = 264) of patients treated for 6 weeks with protactin-raising and prolactin-sparing

  10. 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.

  11. 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.

  12. 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...

  13. Schizophrenia and comorbid cannabis use disorders: Brain structure, function and the effect of antipsychotic medications

    NARCIS (Netherlands)

    Machielsen, M.W.J.

    2014-01-01

    The overall aim of the studies described in this thesis was to increase our understanding of schizophrenia, co-morbid cannabis use disorders and the effects of different antipsychotic medications in patients with schizophrenia and a comorbid cannabis use disorder. Therefore we studied the clinical

  14. Central and Peripheral Mechanisms of Antipsychotic Medication-Induced Metabolic Dysregulation

    Science.gov (United States)

    2016-10-01

    may also significantly contribute to our fundamental understanding of obesity and lead to novel treatments. Since APD-induced metabolic disturbances...York, NY 10032 Department of Psychology , Yeshiva University, New York, NY 10016 Sponsor: Jonathan A. Javitch Background: Antipsychotic drugs...Zachary Freyberg Departments of Psychiatry, Pharmacology & Medicine, Columbia University, New York, NY 10032 Department of Psychology , Yeshiva

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

    Directory of Open Access Journals (Sweden)

    Widen Jan H

    2008-04-01

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

  16. Translational PKPD modeling in schizophrenia: linking receptor occupancy of antipsychotics to efficacy and safety

    NARCIS (Netherlands)

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

    2012-01-01

    Objectives: To link the brain dopamine D2 receptor occupancy (D2RO) of antipsychotic drugs with clinical endpoints of efficacy and safety to assess the therapeutic window of D2RO. Methods: Pharmacokinetic-Pharmacodynamic (PK-PD) models were developed to predict the D2 receptor occupancy of

  17. Brain site- and transmitter-dependent actions of methamphetamine, morphine and antipsychotics.

    Science.gov (United States)

    Mori, Tomohisa; Iwase, Yoshiyuki; Murata, Asami; Iwata, Noriyuki; Suzuki, Tsutomu

    2016-06-01

    While several methamphetamine- and morphine-induced psychotic states are ordinarily treated by antipsychotics, the therapeutic mechanisms of antipsychotic drugs have yet been elucidated. The present study was designed to investigate the mechanisms how antipsychotic drugs suppress the behavioral changes induced by psychoactive drugs in mice. Low to medium doses of methamphetamine produced hyperlocomotion, whereas high dose of methamphetamine induced hypolocomotion. Hyperlocomotion induced by methamphetamine was potently suppressed by clozapine and 5-HT2 receptor antagonists, but not by the intra-accumbens injection of haloperidol. On the other hand, microinjection of haloperidol into the ventrolateral striatum increased locomotor activity with high dose of methamphetamine. In contrast, morphine-induced hyperlocomotion was suppressed by systemic as well as intra-accumbens injection of haloperidol, whereas relatively resistant to clozapine, compared to its effects in the case of methamphetamine. It has been widely believed that methamphetamine-induced psychosis is an animal model of schizophrenia, which is mediated by activation of accumbal dopamine receptors. Our findings suggest that methamphetamine differentially regulate monoaminergic systems (e.g., dopaminergic vs. 5-HTnergic), and accumbal dopamine receptors are not involved in methamphetamine-induced hyperlocomotion in mice. Thus, our findings may lead to a better understanding of the therapeutic mechanisms that underlie the effects of antipsychotic drugs and behavioral effects of methamphetamine and morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose.

    Science.gov (United States)

    Seeman, P

    2016-10-18

    Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.

  19. Management recommendations for metabolic complications associated with second-generation antipsychotic use in children and youth.

    Science.gov (United States)

    Ho, Josephine; Panagiotopoulos, Constadina; McCrindle, Brian; Grisaru, Silviu; Pringsheim, Tamara

    2011-11-01

    Second-generation antipsychotics are commonly associated with metabolic complications. These medications are being used more frequently for the treatment of mental health disorders in children, which has stimulated the need for creating formal guidelines on monitoring their safety and effectiveness. Previous guidelines have been developed for monitoring metabolic and neurological complications. To assist practitioners who perform these monitoring procedures, a complementary set of treatment recommendations have been created for situations in which abnormal measurements or results are encountered. To create evidence-based recommendations to assist in managing metabolic complications in children being treated with second-generation antipsychotics. A systematic review of the literature on metabolic complications of second-generation antipsychotic medications in children was conducted. Members of the consensus group evaluated the information gathered from the systematic review of the literature and used a nominal group process to reach a consensus on treatment recommendations. Wherever possible, references were made to existing guidelines on the evaluation and treatment of metabolic abnormalities in children. Evidence-based recommendations are presented to assist in managing metabolic complications including weight gain; increased waist circumference; elevation in prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function tests and abnormal thyroid studies. The use of second-generation antipsychotics requires proper monitoring procedures. The present treatment guideline provides guidance to clinicians on the clinical management of metabolic complications if they occur.

  20. Prescription of antipsychotic medication to patients at ultra high risk of developing psychosis

    NARCIS (Netherlands)

    Nieman, D.H.; Becker, H.E.; Dingemans, P.M.; van Amelsvoort, T.A.; Haan, L.; van der Gaag, M.; Denys, D.A.J.P.; Linszen, D.H.

    2009-01-01

    Little is known about medication prescription in a naturalistic setting to patients at ultra high risk (UHR) of developing psychosis. Antipsychotic medication prescription to UHR patients is not recommended in clinical practice guidelines based on the current evidence. The aim of this study is to

  1. Early Improvement As a Predictor of Later Response to Antipsychotics in Schizophrenia: A Diagnostic Test Review

    NARCIS (Netherlands)

    Samara, Myrto T.; Leucht, Claudia; Leeflang, Mariska M.; Anghelescu, Ion-George; Chung, Young-Chul; Crespo-Facorro, Benedicto; Elkis, Helio; Hatta, Kotaro; Giegling, Ina; Kane, John M.; Kayo, Monica; Lambert, Martin; Lin, Ching-Hua; Möller, Hans-Jürgen; Pelayo-Terán, José María; Riedel, Michael; Rujescu, Dan; Schimmelmann, Benno G.; Serretti, Alessandro; Correll, Christoph U.; Leucht, Stefan

    2015-01-01

    How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to

  2. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) : Preliminary evidence for reliability and validity

    NARCIS (Netherlands)

    de Boer, M.K.; Castelein, Stynke; Bous, Johan; van den Heuvel, Edwin R.; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

    2013-01-01

    The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia

  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. Estimating Dopamine D-2 Receptor Occupancy for Doses of 8 Antipsychotics : A Meta-Analysis

    NARCIS (Netherlands)

    Lako, Irene M.; van den Heuvel, Edwin R.; Knegtering, Henrikus; Bruggeman, Richard; Taxis, Katja

    2013-01-01

    Rationale: Dose equivalents based on dopamine D-2 receptor occupancy can be used to compare antipsychotics on D-2 receptor-mediated (adverse) effects such as extrapyramidal symptoms and altered emotional experiences. Previous meta-analyses modeling the dose-occupancy relationship hardly addressed

  5. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

    NARCIS (Netherlands)

    J. Sultana (Janet); Calabró, M. (Marco); R. García-Serna (Ricard); C. Ferrajolo (Carmen); Crisafulli, C. (Concetta); J. Mestres (Jordi); G. Trifirò (Gianluca)

    2017-01-01

    textabstractIntroduction: Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim: The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm

  6. Reporting sexual function disorders caused by antipsychotic drugs : is there a role for the community pharmacy?

    NARCIS (Netherlands)

    Rijcken, CAW; Dekens-Konter, JAM; Knegtering, H; de Jong-van den Berg, LTW

    2001-01-01

    Sexual function disorders are frequent adverse effects of antipsychotic use. These effects can lead to non-compliance to medication, which dramatically worsen the outcome of the psychotic disease. Detecting sexual dysfunction by the carers may be difficult, since feelings of embarrassment may occur

  7. Association between the ROBO1 gene and body mass index in patients using antipsychotics

    NARCIS (Netherlands)

    Vehof, Jelle; Al Hadithy, Asmar F. Y.; Burger, Huibert; Snieder, Harold; Risselada, Arne J.; Wilffert, Bob; Cohen, Dan; Arends, Johan; Wiersma, Durk; Mulder, Hans; Bruggeman, Richard

    Background Weight gain is one of the major problems in patients using antipsychotic medication, leading to relevant morbidities and reduced compliance to pharmacotherapy. Recently, an association has been reported between a single nucleotide polymorphism (rs1455832) of the roundabout axon guidance

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

  10. International trends in antipsychotic use : A study in 16 countries, 2005-2014

    NARCIS (Netherlands)

    Hálfdánarson, Óskar; Zoëga, Helga; Aagaard, Lise; Bernardo, Miquel; Brandt, Lena; Fusté, Anna Coma; Furu, Kari; Garuoliené, Kristina; Hoffmann, Falk; Huybrechts, Krista F; Kalverdijk, Luuk J; Kawakami, Koji; Kieler, Helle; Kinoshita, Takuya; Litchfield, Melisa; López, Soffy C; Machado-Alba, Jorge E; Machado-Duque, Manuel E; Mahesri, Mufaddal; Nishtala, Prasad S; Pearson, Sallie-Anne; Reutfors, Johan; Saastamoinen, Leena K; Sato, Izumi; Schuiling-Veninga, Catharina C. M.; Shyu, Yu-Chiau; Skurtveit, Svetlana; Verdoux, Hélène; Wang, Liang-Jen; Yahni, Corinne Zara; Bachmann, Christian J

    2017-01-01

    The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of

  11. 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…

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

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

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

  13. Assessment of monitoring for glucose and lipid dysregulation in adult Medi-Cal patients newly started on antipsychotics.

    Science.gov (United States)

    Barnett, Mitchell; VonMuenster, Shannon; Wehring, Heidi; Popish, Sarah; McDonald, Karna; Walker, Victor M; Perry, Paul

    2010-02-01

    Because patients receiving antipsychotics are at increased risk for coronary heart disease, standards of care for such patients now include periodic glucose and lipid testing. The objective of this study was to examine rates of glucose and lipid monitoring among adult Medicaid patients initiated on antipsychotic therapy. California Medicaid (Medi-Cal) claims of 6601 patients identified as "new" antipsychotic users between July 1, 2004 and June 30, 2005 were analyzed. Rates of glucose and lipid testing were compared for 6 months prior to and post-initiation of antipsychotic therapy. Odds ratios (ORs) for testing associated with first-generation antipsychotic (FGA) and second-generation antipsychotic (SGA) use were determined while controlling for patient level factors. In a multivariate analysis, SGA patients were more likely than FGA patients to undergo glucose testing (OR, 1.38; 95% confidence interval [CI], 1.13 to 1.70; P Medi-Cal patients after initiation of antipsychotic therapy, recommended monitoring does not appear to occur universally in this population. Interventions to increase monitoring of these patients are warranted.

  14. High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia.

    Science.gov (United States)

    Sannohe, Takahiro; Ohnuma, Tohru; Takeuchi, Masayoshi; Tani, Eriko; Miki, Yasue; Takeda, Mayu; Katsuta, Narimasa; Takebayashi, Yuto; Nakamura, Toru; Nishimon, Shohei; Kimoto, Ayako; Higashiyama, Ryoko; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

    2017-06-02

    Carbonyl stress in patients with schizophrenia has been reported to be reflected by an increase in peripheral pentosidine levels. This cohort study tested whether the accumulation of pentosidine was related to the disease severity or the treatment (routine administration of high antipsychotic doses). We followed up our original investigation using a new group of 137 patients with acute schizophrenia and 45 healthy subjects, and then pooled the two cohorts to conduct the following analysis on a total of 274 patients. The associations of serum pentosidine and pyridoxal levels with duration of education, estimated duration of medication, the severity of symptoms, and daily doses of antipsychotics, antiparkinsonian drugs, and anxiolytics were evaluated by multiple linear regression analysis. The combined cohort of 274 patients exhibited abnormally high serum levels of pentosidine, were associated with a higher daily dose of antipsychotic drugs and a longer estimated duration of medication without statistical significance of diagnosis. This was also observed in the patients treated with antipsychotic polypharmacy, but the serum pentosidine levels of patients treated with first- or second-generation antipsychotic monotherapy showed no relationship with these two variables. High levels of serum pentosidine were associated with high daily doses of antipsychotic drugs and a longer estimated duration of medication in patients treated with antipsychotic polypharmacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 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.

  16. 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

  17. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  18. The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder.

    Science.gov (United States)

    Abramovic, Lucija; Boks, Marco P M; Vreeker, Annabel; Bouter, Diandra C; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H; Ophoff, Roel A; Kahn, René S; van Haren, Neeltje E M

    2016-11-01

    There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  19. 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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Alberto Canfrán-Duque

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

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

    Science.gov (United States)

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

    2013-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Stefanović Vesna

    2015-01-01

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

  4. Extract of Synedrella nodiflora (L) Gaertn exhibits antipsychotic properties in murine models of psychosis.

    Science.gov (United States)

    Amoateng, Patrick; Adjei, Samuel; Osei-Safo, Dorcas; Kukuia, Kennedy K E; Bekoe, Emelia Oppong; Karikari, Thomas K; Kombian, Samuel B

    2017-08-07

    The hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) has demonstrated anticonvulsant, sedative and analgesic effects. Preliminary studies conducted in animals, SNE significantly decreased stereotypic behaviours suggesting antipsychotic potential. Coupled with the central nervous system depressant effects of SNE, we hypothesized that it may have utility in the management of psychosis. The present study therefore investigated the antipsychotic potential of the SNE in several murine models of psychosis. The primary central nervous system activities of SNE (30-3000 mg/kg, p.o) were investigated using the Irwin's test. The novelty-induced rearing, locomotion and stereotypy counts provoked by SNE (100-1000 mg/kg, p.o) were conducted using the open-field paradigm. The antipsychotic test models used in the screening of SNE (100-1000 mg/kg, p.o) included apomorphine-induced stereotypy, rearing, locomotion and cage climbing activities. The combined effects of a low dose of SNE (100 mg/kg) with various doses of haloperidol and chlorpromazine were analysed using the apomorphine-induced cage climbing and stereotypy, respectively. The ability of SNE to cause catalepsy in naïve mice as well as its effect on haloperidol-induced catalepsy was assessed. SNE showed acetylcholine-like and serotonin-like activities in the Irwin test, with sedation occurring at high doses. SNE significantly reduced the frequencies of novelty- and apomorphine-induced rearing and locomotion; stereotypy behaviour and the frequency and duration of apomorphine-induced cage climbing in mice. In all the tests performed, SNE was less potent than the reference drugs used (chlorpromazine and haloperidol). In addition, SNE potentiated the effects of haloperidol and chlorpromazine on apomorphine-induced cage climbing and stereotypy activities in mice. SNE, while exhibiting antipsychotic properties itself, can also potentiate the antipsychotic effects of chlorpromazine and haloperidol.

  5. Long-Term Antipsychotic Use and Major Cardiovascular Events: A Retrospective Cohort Study.

    Science.gov (United States)

    Szmulewicz, Alejandro G; Angriman, Federico; Pedroso, Felipe E; Vazquez, Carolina; Martino, Diego J

    Chronic treatment with antipsychotics may result in both metabolic side effects and cardiovascular disease. Our aim was to evaluate the effect of antipsychotic medications categorized by their metabolic side effect profiles as low, intermediate, or high risk on major cardiovascular events. A retrospective cohort study was conducted in adult outpatients aged 30 years or older initiating antipsychotic treatment from 2002 to 2007. Antipsychotic medications were divided into 3 groups (low-, intermediate-, and high-risk) according to the severity of their side-effect profiles in developing metabolic abnormalities associated with cardiovascular disease. The primary outcome measure was the time to the composite of acute myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral artery disease, or a new revascularization procedure. Inverse probability weighting of a marginal structural Cox model was used to adjust for confounding. A total of 1,008 patients were included (mean age = 72.4 years, median follow-up = 36.5 months), and 19.6% of patients experienced the primary outcome. The adjusted hazard ratios of a major cardiovascular event for patients in the high- or intermediate-risk medication groups compared to the low-risk group were 2.82 (95% CI, 1.57-5.05) and 2.57 (95% CI, 1.43-4.63), respectively. Older adult patients under antipsychotic regimens with high or intermediate risk of metabolic side effects may face a higher incidence of major cardiovascular events than those under a low-risk regimen during long-term follow-up. © Copyright 2017 Physicians Postgraduate Press, Inc.

  6. Choice of observational study design impacts on measurement of antipsychotic risks in the elderly: a systematic review

    Science.gov (United States)

    2012-01-01

    Background Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients. Methods We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics. Results Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk

  7. Agent Building Software

    Science.gov (United States)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  8. Competing agents in agent-mediated institutions

    OpenAIRE

    Plaza, Enric; Arcos, Josep Ll.; Noriega, Pablo; Sierra, Carles

    1998-01-01

    Social processes and agent interaction always take place in a specific context. A school of thought in social studies analyses them in the framework of institutions. We present in this paper the notion of agentmediated institutions and show how it is relevant for multi-agent systems (MAS) in general and, more specifically, for MAS that include human agents and software agents involved in socioeconomic interactions. We show how the social interactions of human and software agents taking place ...

  9. Antipsychotic medication in children and adolescents: a descriptive review of the effects on prolactin level and associated side effects.

    NARCIS (Netherlands)

    Roke, Y.; Harten, P.N. van; Boot, A.M.; Buitelaar, J.K.

    2009-01-01

    OBJECTIVE: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. METHOD: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine,

  10. Antipsychotic Medication in Children and Adolescents : A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Boot, Annemieke M.; Buitelaar, Jan K.

    Objective: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. Method: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine,

  11. 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

  12. Neocortical serotonin2A receptor binding predicts quetiapine associated weight gain in antipsychotic-naive first-episode schizophrenia patients

    DEFF Research Database (Denmark)

    Rasmussen, Hans; Ebdrup, Bjørn H; Oranje, B

    2014-01-01

    related serotonin2A receptor binding to weight gain before and after antipsychotic monotherapy. Fifteen antipsychotic-naive first-episode schizophrenia patients were included and investigated before and after six months of quetiapine treatment. We examined the relationship between serotonin2A receptor......Antipsychotic-induced weight gain is of major clinical importance since it is associated with severe metabolic complications and increased mortality. The serotonin2A receptor system has been suggested to be implicated in weight gain and obesity. However, no previous in vivo imaging data have...... to treatment and subsequent increase in BMI (rho = 0.59, p = 0.022). At follow-up, the serotonin2A receptor occupancy was positively correlated with BMI increase (rho = 0.54, p = 0.038). To our knowledge, these are the first in vivo receptor imaging data in initially antipsychotic-naive first...

  13. Antipsychotic treatment, psychoeducation & regular follow up as a public health strategy for schizophrenia: Results from a prospective study

    Directory of Open Access Journals (Sweden)

    Channaveerachari Naveen Kumar

    2017-01-01

    Interpretation & conclusions: Treatment with antipsychotics and psychoeducation can favourably influence the course of schizophrenia and reduce disability in a substantial proportion of patients. Structured psychosocial interventions may be indicated in the significant minority who show suboptimal outcome with this strategy.

  14. Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter; Lublin, H

    2010-01-01

    OBJECTIVE: To evaluate the effect of a multifaceted educational intervention on the frequency of antipsychotic co-prescribing in adult schizophrenia out-patients. METHOD: Controlled quasi-experimental study performed in two Danish municipalities matched for baseline prevalence of antipsychotic...... polypharmacy, socioeconomic status and functional level of patients. The intervention was aimed at psychiatric healthcare providers and consisted of 1 day of didactic lectures, six 3-h educational outreach visits and an electronic reminder during drug prescribing. RESULTS: Between-group use of antipsychotic...... polypharmacy was compared at baseline (intervention group, N = 232/control group, N = 351) and after 1 year of intervention (intervention group, N = 216/control group, N = 386). The prevalence of antipsychotic polypharmacy at follow-up was not significantly different between treatment settings when adjusting...

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

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  16. Tardive dyskinesia in a South Asian population with first episode psychosis treated with antipsychotics

    Directory of Open Access Journals (Sweden)

    Adam UU

    2014-10-01

    Full Text Available Usman Adam, Nusrat Husain, Peter M Haddad, Tariq Munshi, Fauzia Tariq, Farooq Naeem, Imran B ChaudhryBackground: Tardive dyskinesia (TD is a side effect of antipsychotic treatment that often only appears after months or years of treatment. A systematic review of randomized controlled trials lasting more than 1 year showed that second-generation antipsychotics (SGAs were associated with an approximately fivefold lower risk of TD compared to haloperidol in patients with chronic schizophrenia. In contrast, there is little research on the risk of TD with other first-generation antipsychotics (FGAs, and this applies especially to their use in the treatment of patients with first episode psychosis (FEP.Objectives: To determine the severity and point prevalence of TD in a naturalistic sample of patients with FEP in Pakistan treated with FGAs or SGAs.Methods: This was an observational study. TD was assessed by trained clinicians using the Abnormal Involuntary Movement Scale.Results: In the total sample (number =86 the mean age of patients was 26 years and the prevalence of TD (Schooler Kane criteria was 29% with no significant difference between those treated with FGAs and SGAs (31% FGAs versus 26% SGAs; P=0.805. The Abnormal Involuntary Movement Scale total score (items 1–7, a measure of the severity of TD, was significantly higher for patients treated with FGAs versus those treated with SGAs (P=0.033. Scores on specific items showed that this reflected higher scores for dyskinesia affecting the muscles of facial expression, as well as of the upper and lower limb, whereas scores did not differ significantly in other body areas. Conclusion: FGAs were associated with greater severity, though not prevalence, of TD than SGAs. The study highlights the relatively high rate of TD in Asian FEP patients and the need for clinicians to monitor for this and other potential antipsychotic side effects during treatment. Keywords: first-generation antipsychotic

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

    Directory of Open Access Journals (Sweden)

    Hansen Karina

    2008-03-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  19. Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Hans; Erritzoe, David; Andersen, Rune

    2010-01-01

    , in vivo studies of serotonin(2A) binding report conflicting results, presumably because sample sizes have been small or because schizophrenic patients who were not antipsychotic-naive were included. Furthermore, the relationships between serotonin(2A) binding, psychopathology, and central neurocognitive......Postmortem investigations and the receptor affinity profile of atypical antipsychotics have implicated the participation of serotonin(2A) receptors in the pathophysiology of schizophrenia. Most postmortem studies point toward lower cortical serotonin(2A) binding in schizophrenic patients. However...

  20. 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.

  1. Prolactin concentrations in antipsychotic-naïve patients with schizophrenia and related disorders: A meta-analysis.

    Science.gov (United States)

    González-Blanco, Leticia; Greenhalgh, Anne Marie D; Garcia-Rizo, Clemente; Fernandez-Egea, Emilio; Miller, Brian J; Kirkpatrick, Brian

    2016-07-01

    The use of dopaminergic antagonist antipsychotics is associated with hyperprolactinemia, but some studies have found increased prolactin concentrations in antipsychotic-naive patients with schizophrenia and related disorders. We conducted a systematic review and meta-analysis of studies of prolactin in antipsychotic-naïve patient with these disorders (PRISMA No. CRD42015016337). PubMed (Medline), PsycInfo, and Web of Science were searched for articles from 1950 to the present in English. Seven studies of males (N=141 for patients, N=191 for control subjects) and five studies of females (N=67 and N=116) met criteria for inclusion: data on blood prolactin concentrations for both control subjects and antipsychotic-naive patients with schizophrenia or a related disorder, with data available separately for males and females. Data was extracted from the papers by one author and independently verified by a second. The mean effect size for males was 1.02 (95% CI, 0.77, 1.26; pprolactin levels in both male and female antipsychotic-naïve patients with schizophrenia and related disorders. The small number of studies and limited matching for potentially confounding variables in some of the studies were limitations of this analysis. Prolonged hyperprolactinemia may lead to sexual dysfunction and osteoporosis, and some antipsychotics cause additional elevation of prolactin concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. 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.

  3. [The relationship between antipsychotic-induced hyperprolactinemia and menstrual disorders in women with schizophrenia; a systematic review].

    Science.gov (United States)

    Ouwehand, A J; Mollema-Schelwald, B M; Knegtering, H

    2012-01-01

    Menstrual disorders are common among women with schizophrenia, particularly when they are being treated with antipsychotics. The occurrence of menstrual disorders is often attributed to the use of prolactin-elevating antipsychotics, although menstrual disorders also occur in patients not using antipsychotics. Therefore we need to find out whether menstrual disorders in schizophrenia are drug-related or whether they have some other connection with schizophrenia. To identify and discuss studies that investigate the relationship between antipsychotics-induced hyperprolactinemia and menstrual disorders in women with schizophrenia. We reviewed the literature systematically using PubMed, Psyc, info and the Cochrane Central Register of Controlled Trials. Very few studies have investigated the connection between antipsychotic-induced hyperprolactinemia and menstrual disorders and most have serious methodological limitations. Only one study was able to demonstrate such a connection. On the basis of current research no firm conclusions can be drawn about the relationship between the increased frequency of menstrual disorders in women with schizophrenia and elevated prolactin levels resulting from the use of antipsychotics.

  4. Early perception of medication benefit predicts subsequent antipsychotic response in schizophrenia: "the consumer has a point" revisited.

    Science.gov (United States)

    Ascher-Svanum, Haya; Weiden, Peter; Nyhuis, Allen W; Faries, Douglas E; Stauffer, Virginia; Kollack-Walker, Sara; Kinon, Bruce J

    2014-07-01

    An easy-to-administer tool for predicting response to antipsychotic treatment could improve the acute management of patients with schizophrenia. We assessed whether a patient's perception of medication benefit early in treatment could predict subsequent response or nonresponse to continued use of the same treatment. This post hoc analysis used data from a randomized, open-label trial of antipsychotics for treatment of schizophrenia in which attitudes about medication adherence were assessed after two weeks of antipsychotic treatment using the Rating of Medication Influences (ROMI) scale. The analysis included 439 patients who had Positive and Negative Syndrome Scale (PANSS) and ROMI scale data at Weeks 2 and 8. Scores on the ROMI subscale Perceived Medication Benefit factor were used to predict subsequent antipsychotic response at Week 8, defined as a .20% reduction from baseline on the PANSS. Logistic regression was used to identify a cut-off score for the Perceived Medication Benefit factor that could accurately identify antipsychotic responders vs. nonresponders at Week 8. A score of .2.75 (equal to a mean subscale score of .11.00) on the ROMI scale Perceived Medication Benefit factor at Week 2 predicted response at Week 8 with high specificity (72%) and negative predictive value (70%), moderate sensitivity (44%) and positive predictive value (47%), and with a 38% misclassification rate. A brief assessment of the patient's perception of medication benefit at two weeks into treatment appears to be a good predictor of subsequent response and nonresponse after eight weeks of treatment with the same antipsychotic.

  5. The Effectiveness and Safety of Antipsychotic and Antidepressant Medications in Individuals with 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Dori, Netta; Green, Tamar; Weizman, Abraham; Gothelf, Doron

    2017-02-01

    The purpose of this study was to evaluate the effectiveness and safety of antipsychotic and antidepressant medications in individuals with 22q11.2 deletion syndrome (22q11.2 DS) and psychiatric comorbidity. We used a record review, structured clinical interviews, and the Clinical Global Impressions (CGI) scale to retrospectively assess the effectiveness and safety of antipsychotic medications for schizophrenia spectrum disorders and of antidepressant medications for depressive and anxiety disorders in 40 individuals with 22q11.2DS. We observed significant improvement in CGI-Severity scores in individuals with 22q11.2DS treated with antipsychotic or antidepressant medications, and a ∼50% response rate based on the CGI-Improvement score. Adverse events were similar in types and rates to those reported in non-22q11.2 individuals treated with antipsychotics or antidepressants. Our data show that treatment with antipsychotics and antidepressants may be effective while being relatively safe in individuals with 22q11.2DS. Antipsychotic and antidepressant medications should be considered in any individual with 22q11.2DS who has a psychiatric morbidity, such as psychosis or mood or anxiety disorders. Although the psychotropic medications were generally well tolerated in our sample, more rigorous metabolic and cardiovascular measures are required in future studies to conclusively verify the safety of these medications.

  6. The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects.

    Science.gov (United States)

    Hashimoto, Naoki; Ito, Yoichi M; Okada, Naohiro; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Kudo, Noriko; Takemura, Ariyoshi; Son, Shuraku; Narita, Hisashi; Yamamoto, Maeri; Tha, Khin Khin; Katsuki, Asuka; Ohi, Kazutaka; Yamashita, Fumio; Koike, Shinsuke; Takahashi, Tsutomu; Nemoto, Kiyotaka; Fukunaga, Masaki; Onitsuka, Toshiaki; Watanabe, Yoshiyuki; Yamasue, Hidenori; Suzuki, Michio; Kasai, Kiyoto; Kusumi, Ichiro; Hashimoto, Ryota

    2018-01-01

    The effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis. Imaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed. Daily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes. A large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication.

  7. Association between Antipsychotic Drugs and Mortality in Older Persons with Alzheimer's Disease: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Zhai, Yaoming; Yin, Song; Zhang, Dongfeng

    2016-03-31

    Antipsychotic drugs have been inconsistently associated with death risk of Alzheimer's disease (AD) patients. Herein we review and quantitatively summarize the evidence from epidemiological studies. Pertinent studies were identified by searching PubMed and Cochrane Library Register of Controlled Trials through 20 December 2015. The DerSimonian and Laird random effect model was adopted as the pooling method. Twelve studies from nine articles with 11,463 participants were included. The pooled RR of observational studies was 1.36 (95% CI, 0.83-2.24; I2 = 94.9%) for antipsychotic drugs users versus individuals who were not exposed to antipsychotic drugs. When the three studies that were key contributors to the high heterogeneity were excluded, the pooled RR was 2.08 (95% CI 1.39 to 3.13). The result of one double-blind randomized clinical trial indicated that antipsychotic drugs nearly doubled the risk of death in AD patients. In conclusion, there is no evidence of absence of association between antipsychotic drugs' use with death risk of AD patients. Careful assessments of potential benefits and risks should be made before prescribing antipsychotics for treatment of psychosis symptoms and behavioral problems of AD patients.

  8. [Eating disorders in psychiatric patients during treatment with second generation antipsychotics].

    Science.gov (United States)

    Vasilenko, L M; Gorobets, L N; Bulanov, V S; Litvinov, A V; Ivanova, G P; Tsarenko, M A; Polyakovskaya, T P

    2015-01-01

    To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMIobesity grade 2-3 in 38 patients (BMI>30 kg/m²). Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these we developed recommendations for management of patients treated with second generation antipsychotics.

  9. Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry

    DEFF Research Database (Denmark)

    Kiss, A; Bundzikova, J; Pirnik, Z

    2010-01-01

    of risperidone and haloperidol. Variabilities in Fos distribution in the PVN, SON, and ACS induced by antipsychotics may be helpful to understand more precisely the extent of their extra-forebrain actions with possible presumption of their functional impact and side effect consequences....... accessory (ACS) cell groups, and 4 distinct PVN subdivisions using a computerized light microscope. Most apparent activation of single Fos, Fos/OXY, and Fos/AVP cells was induced by clozapine and olanzapine; effects of risperidone and haloperidol were substantially lower; no colocalizations were revealed...... in naive or vehicle treated control rats. The data indicate the existence of a substantial diversity in the stimulatory effect of the selected antipsychotics on quantity of Fos, Fos/OXY, and Fos/AVP immunostainings with the preferential action of the atypicals clozapine over olanzapine and little effects...

  10. Synthesis, docking and pharmacological evaluation of novel indole based potential atypical antipsychotics.

    Science.gov (United States)

    Bali, Alka; Sen, Umesh; Peshin, Tania

    2014-03-03

    A series of substituted indole derivatives have been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypy assays in mice. The compounds 11 and 12 have emerged as important lead compounds showing potential atypical antipsychotic profile. In silico (docking studies) have been carried out to postulate a hypothetical binding model for the target compounds with respect to the dopaminergic D2 and 5-HT2A receptors. Theoretical ADME profiling of the compounds based on selected physicochemical parameters has suggested an excellent compliance with Lipinski's rules. The potential of these compounds to penetrate the blood brain barrier (log BB) was computed through an online software program and the values obtained for the compounds suggest good potential for brain permeation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte; Rasmussen, Hans

    2010-01-01

    enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia. METHODS: We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched...... healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use...... that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared...

  12. Consumer satisfaction with antipsychotic medication-monitoring appointments: the role of consumer-prescriber communication patterns.

    Science.gov (United States)

    Reich, Catherine M; Hack, Samantha M; Klingaman, Elizabeth A; Brown, Clayton H; Fang, Li Juan; Dixon, Lisa B; Jahn, Danielle R; Kreyenbuhl, Julie A

    2018-06-01

    The study was designed to explore patterns of prescriber communication behaviors as they relate to consumer satisfaction among a serious mental illness sample. Recordings from 175 antipsychotic medication-monitoring appointments between veterans with psychiatric disorders and their prescribers were coded using the Roter Interaction Analysis System (RIAS) for communication behavioral patterns. The frequency of prescriber communication behaviors (i.e., facilitation, rapport, procedural, psychosocial, biomedical, and total utterances) did not reliably predict consumer satisfaction. The ratio of prescriber to consumer utterances did predict consumer satisfaction. Consistent with client-centered care theory, antipsychotic medication consumers were more satisfied with their encounters when their prescriber did not dominate the conversation. Therefore, one potential recommendation from these findings could be for medication prescribers to spend more of their time listening to, rather than speaking with, their SMI consumers.

  13. 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 contribu