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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 references352

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          Antipsychotic-induced weight gain: a comprehensive research synthesis.

          The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.
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            Excess mortality in bipolar and unipolar disorder in Sweden.

            Selected groups of patients with bipolar and unipolar disorder have an increased mortality rate from suicide and natural causes of death. However, there has been no population-based study of mortality of patients followed up from the onset of the illness. All patients with a hospital diagnosis of bipolar (n = 15 386) or unipolar (n = 39 182) disorder in Sweden from 1973 to 1995 were identified from the inpatient register and linked with the national cause-of-death register to determine the date and cause of death. Overall and cause-specific standardized mortality ratios (SMRs) and numbers of excess deaths were calculated by 5-year age classes and 5-year calendar periods. The SMRs for suicide were 15.0 for males and 22.4 for females with bipolar disorder, and 20.9 and 27.0, respectively, for unipolar disorder. For all natural causes of death, SMRs were 1.9 for males and 2.1 for females with bipolar disorder, and 1.5 and 1.6, respectively, for unipolar disorder. For bipolar disorder, most excess deaths were from natural causes, whereas for unipolar disorder, most excess deaths were from unnatural causes. The SMR for suicide was especially high for younger patients during the first years after the first diagnosis. Increasing SMR for suicide during the period of study was found for female patients with unipolar disorder. This population-based study of patients treated in the hospital documented increased SMRs for suicide in patients with bipolar and unipolar disorder. The SMR for all natural causes of death was also increased, causing about half the excess deaths.
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              Metabolic syndrome in people with schizophrenia: a review.

              Metabolic syndrome and other cardiovascular risk factors are highly prevalent in people with schizophrenia. Patients are at risk for premature mortality and overall have limited access to physical health care. In part these cardio-metabolic risk factors are attributable to unhealthy lifestyle, including poor diet and sedentary behaviour. But over recent years it has become apparent that antipsychotic agents can have a negative impact on some of the modifiable risk factors. The psychiatrist needs to be aware of the potential metabolic side effects of antipsychotic medication and to include them in the risk/benefit assessment when choosing a specific antipsychotic. He should also be responsible for the implementation of the necessary screening assessments and referral for treatment of any physical illness. Multidisciplinary assessment of psychiatric and medical conditions is needed. The somatic treatments offered to people with severe and enduring mental illness should be at par with general health care in the non-psychiatrically ill population.
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                Author and article information

                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
                : e94112
                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.

                Article
                PONE-D-13-29604
                10.1371/journal.pone.0094112
                3998960
                24763306
                8aae717d-a41e-495f-9c15-d5c70d222138
                Copyright @ 2014

                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.

                History
                : 2 July 2013
                : 12 March 2014
                Page count
                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
                Uncategorized

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