Influence of topiramate on olanzapine-related adiposity in women: a random, double-blind, placebo-controlled study.
ABSTRACT The aim of this study was to compare the efficacy of topiramate versus a placebo in the treatment of adiposity in women undergoing olanzapine therapy. We also assessed changes health-related quality of life, the patient's actual state of health, and psychologic impairments. The 10-week, random, double-blind, placebo-controlled study included 43 women who had been treated with olanzapine (mean dose 7.8 +/- 3.6 in the topiramate group and 7.2 +/- 3.1 in the placebo group) and had gained weight as a side effect. The subjects were randomly assigned to topiramate (n = 25) or a placebo (n = 18). Primary outcome measures were weight checks and self-reported changes on the scales of the SF-36 Health Survey, Bf-S Scale of Well-Being, and the Adjective Checklist EWL-60-S. Weight loss was observed and was significantly more pronounced in the topiramate-treated group (difference in weight loss between the 2 groups: 5.6 kg, 95% CI = -8.5, -3.0, P < 0.001). In comparison with the placebo group, significant changes on 7 (7/8) scales of SF-36 Health Survey (all P < 0.001), on all 6 scales of the EWL-60-S, and on the Bf-S were observed in the topiramate-treated subjects after 10 weeks. All patients tolerated topiramate well. Topiramate appears to be a safe and effective agent in the treatment of weight gain that occurred during olanzapine treatment. Significantly positive changes in health-related quality of life, the patient's actual state of health, and psychologic impairments were observed.
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ABSTRACT: Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of Science, PsycNET, and EMBASE for randomized, open and double-blind, placebo-controlled trials of medications targeting antipsychotic-induced weight gain was performed. Primary outcome measures were change and endpoint values in body weight and body mass index (BMI). Secondary outcomes included >or=7% weight gain, all-cause discontinuation, change in waist circumference, glucose and lipid metabolism parameters, and psychiatric symptoms. Sensitivity analyses were conducted to explain heterogeneity of the results. Across 32 studies including 1482 subjects, 15 different medications were tested: amantadine, dextroamphetamine, d-fenfluramine, famotidine, fluoxetine, fluvoxamine, metformin, nizatidine, orlistat, phenylpropanolamine, reboxetine, rosiglitazone, sibutramine, topiramate, and metformin+sibutramine. Compared with placebo, metformin had the greatest weight loss (N=7, n=334, -2.94 kg (confidence interval (CI:-4.89,-0.99)), followed by d-fenfluramine (N=1, n=16, -2.60 kg (CI:-5.14,-0.06)), sibutramine (N=2, n=55, -2.56 kg (CI:-3.91,-1.22)), topiramate (N=2, n=133, -2.52 kg (CI:-4.87,-0.16)), and reboxetine (N=2, n=79, -1.90 kg (CI:-3.07,-0.72)). Weight loss remained significant with metformin initiation after weight gain had occurred, but not when started concomitantly with antipsychotics. Nausea rates were not higher with any treatment compared with placebo. In all, 5 of 15 psychopharmacologic interventions aimed at ameliorating antipsychotic-induced weight gain outperformed placebo. Results were most robust for metformin, although these were modest and heterogeneous. Only one (negative) combination treatment study was available and head-to-head studies are absent. None of the agents were able to entirely reverse weight gain because of antipsychotics. At present, no treatment has sufficient evidence to recommend broad clinical usage. Antipsychotics with no or minimal cardiometabolic liability, as well as interventions that prevent or normalize adverse antipsychotic cardiometabolic effects are needed.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2010; 35(7):1520-30. DOI:10.1038/npp.2010.21 · 7.83 Impact Factor
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ABSTRACT: Obesity is a global epidemic and a health priority, and several psychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia, are associated with an elevated risk of comorbid obesity. Moreover, persons with psychiatric disorders often have multiple risk factors (e.g., poverty and use of psychotropic medications) for excess weight. Excess weight in turn is associated with serious health consequences, both medical and psychiatric. Mental health care professionals must be familiar with the appropriate screening and treatment strategies for obesity. The authors provide a syn- thesis of the epidemiology, psychiatric and medical consequences, risk factors, and management strate- gies for obesity in psychiatric populations, giving particular consideration to management of the psychiatric patient who experiences psychotropic-associated weight gain. To formulate answers to 10 commonly asked questions about obesity and mental health, the authors conducted a MEDLINE search of all English-language articles published between 1966 and June 2005. The search terms were obesity, overweight, body mass index (BMI), metabolism, bariatric treatment, weight-loss treatment, major depressive disorder, bipolar disorder, schizophrenia, binge-eating disorder, eating disorder, and psychotropic medication. The search was supplemented with a manual review of relevant references.10/2005; 3(4). DOI:10.1176/foc.3.4.511
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ABSTRACT: APA's Practice Guideline for the Treatment of Patients With Schizophrenia, Second Edition, was published in April 2004 (1). This watch highlights key research studies published since that date. The studies were identified by a MEDLINE literature search for meta-analyses and randomized, con-trolled trials published between 2002 and 2008, using the same key words used for the literature search performed for the 2004 guideline. With regard to pharmacotherapy, there have been sev-eral important randomized trials of antipsychotics. For chronic schizophrenia, trials include the National Insti-tute of Mental Health (NIMH) Clinical Antipsychotic Trial for Intervention Effectiveness (CATIE) and the United Kingdom–funded Cost Utility of the Latest Antipsychotics in Schizophrenia (CUtLASS). For first-episode schizophrenia, there are two industry-funded trials, the European First Episode Schizophrenia Trial (EUFEST)—funded by AstraZeneca, Pfizer, and Sanofi-Aventis—and the Comparison of Atypicals for First Epi-sode Schizophrenia (CAFE)—funded by AstraZeneca. For early-onset schizophrenia, there is one trial, the NIMH-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). These trials point to a re-consideration of treatment with the antipsychotics per-phenazine and molindone and by extension other first-generation antipsychotics, with the possible exception of haloperidol, for which some trials have shown greater rates of extrapyramidal side effects or less favorable clinical re-sponse (2). In addition, a recent population-based cohort study (3) that encompassed 11 years of follow-up showed decreased rates of mortality with perphenazine as compared with other first-and second-generation antipsychotic agents; only clozapine use was associated with lower rates of overall mortality. For the period April 2008 to August 2009, Dr. Dixon reports attending a consultation meeting for Janssen and receiving a grant from Bristol-Meyers-Squibb for investigator-initiated research, Dr. Perkins reports receiving research funding from Janssen (ended Janu-ary 2009) and reports receiving income for consulting for Dainippon (data safety monitoring board on lurasidone studies) and for serving on speakers bureaus for Eli Lilly, and Dr. Calmes reports no competing interests. The Executive Committee on Practice Guidelines reviewed this watch and found no evidence of influence from these relationships. The American Psychiatric Association's (APA's) practice guidelines are developed by expert work groups using an explicit meth-odology that includes rigorous review of available evidence, broad peer review of iterative drafts, and formal approval by the APA Assembly and Board of Trustees. APA practice guidelines are intended to assist psychiatrists in clinical decision making. They are not intended to be a standard of care. The ultimate judgment regarding a particular clinical procedure or treatment plan must be made by the psychiatrist in light of the clinical data presented by the patient and the diagnostic and treatment options available. Guideline watches summarize significant developments in practice since publication of an APA practice guideline. Watches may be authored and reviewed by experts associated with the original guideline development effort and are approved for publication by APA's Executive Committee on Practice Guidelines. Thus, watches represent opinion of the authors and approval of the Executive Committee but not policy of the APA. This guideline watch was published in September 2009.