Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis.
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ABSTRACT:
SUBMITTER: Geddes J
PROVIDER: S-EPMC27538 | biostudies-literature | 2000 Dec
REPOSITORIES: biostudies-literature
Publications
Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis.
Geddes J J Freemantle N N Harrison P P Bebbington P P
BMJ (Clinical research ed.) 20001201 7273
<h4>Objective</h4>To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia.<h4>Design</h4>Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines.<h4>Subjects</h4>12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperi ...[more]
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Project description:BackgroundAntipsychotics improve the positive symptoms of schizophrenia. However, little is known about the extent of antidepressive effects of antipsychotics and their correlation with effects on other symptom domains in schizophrenia. The aim was to investigate whether antidepressive effects of antipsychotics have a significant correlation with the effects on specific symptom domains of schizophrenia.MethodsElectronic databases were searched to identify eligible studies that reported antidepressive effects of antipsychotics for the treatment of adult patients with schizophrenia in double-blind, randomized placebo-controlled trials (RCTs). Mean change from baseline in depressive symptoms was meta-analyzed, and the correlation with the effects on other symptom domains was examined through meta-regression analysis.ResultsThirty-five RCTs (13 890 patients) were included in this meta-analysis. Overall, antipsychotics showed greater efficacy than placebo in reducing depressive symptoms, with small to medium effect sizes (standardized mean difference = -0.27, 95% confidence interval -0.32 to -0.22, P < .001). All the antipsychotics, except for chlorpromazine, haloperidol, and ziprasidone, were associated with significantly greater decreases in depressive symptoms compared with placebo (standardized mean difference = -0.19 to -0.40). A higher antidepressive effect was significantly correlated with a higher improvement in Positive and Negative Syndrome Scale/Brief Psychiatric Rating Scale total, positive, and negative, and Positive and Negative Syndrome Scale-general psychopathology symptoms (β = .618, P < .001; β = .476, P < .001; β = .689, P < .001; β = .603, P < .001, respectively).ConclusionsSecond-generation antipsychotics (except for ziprasidone) were associated with small to medium effects sizes on improvement in depressive symptoms among adult patients with schizophrenia. The antidepressive effect of antipsychotics was significantly correlated with improvement in other symptom domains, with the highest correlation observed for improvement in negative symptoms.Prospero registration numberCRD42019133015.
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Project description:PurposeTo assess the present evidence regarding the efficiency, safety, and potential risks of pharmacotherapy used for Parkinson's disease psychosis (PDPsy) treatment.Patients and methodsWe searched the following databases: PubMed, the Cochrane Library, ISI Web of Science, and Embase using the following terms: atypical antipsychotics, pimavanserin, olanzapine, quetiapine, clozapine, Parkinson's disease and psychosis. We systematically reviewed all randomized placebo-controlled trials comparing an atypical antipsychotic with a placebo.ResultsA total of 13 randomized placebo-controlled trials for a total 1142 cases were identified involving pimavanserin (n=4), clozapine (n=2), olanzapine (n=3), and quetiapine (n=4). For each atypical antipsychotic, a descriptive synthesis and meta-analyses was presented. Pimavanserin was associated with a significant improvement in psychotic symptoms compared to a placebo without worsening motor function. Clozapine was efficacious in alleviating psychotic symptoms and did not exacerbate motor function either. Quetiapine and Olanzapine did not demonstrate significant differences in reducing psychotic symptoms but may aggravate motor function.ConclusionsThere is strong evidence that pimavanserin is effective for the treatment of PDPsy. Clozapine is also recommended but should be used with caution due to its side effects. In the future, more well-designed randomized controlled trials (RCTs) are needed to confirm and update the findings reported in this meta-analysis.
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Project description:BackgroundAntipsychotics are the treatment of choice in the therapy of schizophrenia. These drugs can be associated with changes in heart rate, but this question has never been examined systematically.ObjectiveWe aimed to analyse changes in heart rate during treatment with antipsychotics using the frequency of tachycardia and bradycardia events.DesignFor this systematic review and meta-analysis, we included all randomized controlled trials for the acute treatment of schizophrenia comparing antipsychotics head-to-head or with placebo.Data sources and methodsWe searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform and ClinicalTrials.gov (last search June 2021). Two authors independently selected studies and extracted data. We conducted pairwise meta-analyses using a random-effects model. Outcomes were tachycardia and bradycardia events.ResultsWe found 469 trials meeting the inclusion criteria. Seventy-seven studies with 16,907 participants provided data on tachycardia or bradycardia events. We found no significant differences between antipsychotics and placebo or between antipsychotics for bradycardia events based on sparse data. Antipsychotics had a higher risk for tachycardia events compared with placebo [N = 37, n = 7827, risk ratio (RR) = 1.83, 95% confidence interval (CI) = 1.40-2.41], with large differences between the individual substances (iloperidone RR = 14.05, chlorpromazine RR = 4.84, loxapine RR = 4.52, risperidone RR = 3.38, quetiapine RR = 2.64, paliperidone RR = 1.65). Some head-to-head comparisons were also significantly different: olanzapine versus haloperidol RR = 2.87, chlorpromazine versus thiothixene RR = 2.92, quetiapine versus lurasidone RR = 3.22, risperidone versus aripiprazole RR = 4.37, iloperidone versus ziprasidone RR = 4.65).ConclusionMany studies do not report data for cardiac outcomes, but the available evidence indicates that treatment with antipsychotics raises the risk for tachycardia. Therefore, especially patients with cardiac risk factors should be monitored closely during antipsychotic treatment.RegistrationPROSPERO: CRD42014014919.
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Project description: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 (D(2)/5-HT(2A)) antagonist structurally related to risperidone, expected to give better efficacy with less extrapyramidal symptoms than D(2) 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.
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Project description:BackgroundIn 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.ObjectivesTo evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.Search strategyWe searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO.Selection criteriaWe 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 analysisWe 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 resultsThe 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). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67).Authors' conclusionsThere is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.
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Project description:CrossFit is recognized as one of the fastest growing high-intensity functional training modes in the world. However, scientific data regarding the practice of CrossFit is sparse. Therefore, the objective of this study is to analyze the findings of scientific literature related to CrossFit via systematic review and meta-analysis.Systematic searches of the PubMed, Web of Science, Scopus, Bireme/MedLine, and SciELO online databases were conducted for articles reporting the effects of CrossFit training. The systematic review followed the PRISMA guidelines. The Oxford Levels of Evidence was used for all included articles, and only studies that investigated the effects of CrossFit as a training program were included in the meta-analysis. For the meta-analysis, effect sizes (ESs) with 95% confidence interval (CI) were calculated and heterogeneity was assessed using a random-effects model.Thirty-one articles were included in the systematic review and four were included in the meta-analysis. However, only two studies had a high level of evidence at low risk of bias. Scientific literature related to CrossFit has reported on body composition, psycho-physiological parameters, musculoskeletal injury risk, life and health aspects, and psycho-social behavior. In the meta-analysis, significant results were not found for any variables.The current scientific literature related to CrossFit has few studies with high level of evidence at low risk of bias. However, preliminary data has suggested that CrossFit practice is associated with higher levels of sense of community, satisfaction, and motivation.
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Project description:The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug-drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient's needs and treatment goals.
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Project description:The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine.We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis.We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine.Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient.
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Project description:BackgroundSchizophrenia is associated with significant economic burden. In Brazil, antipsychotic drugs and outpatient and hospital services are provided by the Brazilian National Health System (SUS) for patients with schizophrenia. However, few studies capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems.ObjectiveOur objective was to use real-world data to describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010.MethodsWe integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. We assessed only direct medical costs and the study was conducted from a public-payer perspective. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables.ResultsWe identified 174,310 patients with schizophrenia, with mean ± standard deviation (SD) annual costs of $US1811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of total costs, with a mean annual cost per patient of $US1578.74 ± 240.40. Mean annual costs per patient were $US2482.90 ± 302.92 for psychiatric hospitalization and $US862.96 ± 160.18 for outpatient psychiatric care. Olanzapine was used by 47.7% of patients and represented 62.8% of the total costs of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient for outpatient psychiatric care and psychiatric hospitalization.ConclusionsAtypical antipsychotics were responsible for the majority of the schizophrenia treatment costs, and psychiatric hospitalization costs were the highest mean annual cost per patient. Authorities should ensure efficient use of atypical antipsychotics and encourage outpatient psychiatric care over psychiatric hospitalization where possible.
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