title: Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis.
abstract: BACKGROUND
  Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option.
  
  
  OBJECTIVE
  To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia.
  
  
  METHODS
  Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan;
authors.forename: Yuya
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Inokashira Hospital, Tokyo, Japan;
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan;
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan;
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan;
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria;
authors.forename: Walter Wolfgang
authors.initials: WW
authors.lastname: Fleischhacker
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada hiroyuki.uchida.hu@gmail.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D006801:Humans; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents
keywords: PRISMA; antipsychotic; concomitant; meta-analysis; metabolic; schizophrenia