Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments

Ann Clin Psychiatry. 2012 Aug;24(3):225-39.


Background: Weight gain in schizophrenia, particularly secondary to second-generation antipsychotic (SGA) use, is a common adverse effect and often is associated with significant physical and psychological morbidity.

Methods: We performed a critical literature review of all controlled clinical trials for pharmacologic and/or behavioral management of SGA-induced weight gain in schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis was performed to estimate and compare weight changes for various medications and behavioral interventions.

Results: Sample sizes generally were small. Clinical trials were 6 weeks to 1 year, and weight loss was modest with any treatment. Although several adjunctive pharmacologic treatments showed no weight loss, sibutramine, metformin, and topiramate showed some benefit. Amantadine and orlistat were somewhat less effective and had lower rates of tolerability. Among the behavioral therapies, nutritional counseling combined with exercise showed the most benefit. Behavioral therapies, although modest, showed the most consistent benefits compared with controls.

Conclusions: Scheduled pharmacologic treatment to prevent weight gain or promote weight loss in schizophrenia patients on SGA therapy is limited based on current studies. Switching antipsychotic agents has not been established as a long-term solution. Additional long-term studies are required to influence clinical practice.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anti-Obesity Agents / therapeutic use*
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Humans
  • Obesity / chemically induced*
  • Obesity / therapy*
  • Schizophrenia / drug therapy*
  • Weight Gain / drug effects
  • Weight Reduction Programs / methods*


  • Anti-Obesity Agents
  • Antipsychotic Agents