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Almost All Antipsychotics Result in Weight Gain: A Meta-Analysis

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      Abstract

      Introduction

      Antipsychotics (AP) induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA) and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer.

      Method

      A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss). Duration of AP-use was stratified as follows: ≤6 weeks, 6–16 weeks, 16–38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures.

      Results

      307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP.

      Conclusion

      Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.

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      Most cited references 402

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      Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.

       T Sipe,  D Rennie,  D Stroup (2000)
      Because of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers. Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention. We conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods. From the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed. The proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.
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        Meta-analysis of Observational Studies in EpidemiologyA Proposal for Reporting

         Donna Stroup (2000)
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          Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

          The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism. Copyright 2005 Massachusetts Medical Society.
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            Author and article information

            Affiliations
            [1 ]Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
            [2 ]Maxima Medical Centre Dep. of gynaecology, Veldhoven, The Netherlands
            [3 ]King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom
            Baylor College of Medicine, United States of America
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            Conceived and designed the experiments: MB JvO. Analyzed the data: MD JvO MB. Wrote the paper: MB AF JJ JvO MD. Performed the article search: MB AF JJ. Computed the data base: MB AF MD. Performed the statistical analysis of this paper: MB JvO MD. Supervised the process: JvO.

            Contributors
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, USA )
            1932-6203
            2014
            24 April 2014
            : 9
            : 4
            24763306 3998960 PONE-D-13-29604 10.1371/journal.pone.0094112

            This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Counts
            Pages: 19
            Funding
            These authors have no support or funding to report.
            Categories
            Research Article
            Medicine and Health Sciences
            Mental Health and Psychiatry
            Mental Health Therapies
            Drug Psychotherapy
            Psychoses
            Schizophrenia
            Pharmacology
            Drug Research and Development
            Drug Interactions
            Adverse Reactions
            Clinical Pharmacology
            Psychopharmacology
            Clinical Medicine
            Physical Sciences
            Mathematics
            Statistics (Mathematics)
            Statistical Methods
            Meta-Analysis
            Research and Analysis Methods
            Research Design
            Clinical Research Design

            Uncategorized

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