Antipsychotic-induced weight gain: a comprehensive research synthesis

Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.


Objective: 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.

Method: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Clinical Trials as Topic / statistics & numerical data
  • Clozapine / adverse effects
  • Clozapine / therapeutic use
  • Confidence Intervals
  • Drug Administration Schedule
  • Humans
  • Molindone / adverse effects
  • Molindone / therapeutic use
  • Piperazines / adverse effects
  • Piperazines / therapeutic use
  • Placebos
  • Psychotic Disorders / drug therapy
  • Research Design / standards
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use
  • Treatment Outcome
  • Weight Gain / drug effects*


  • Antipsychotic Agents
  • Piperazines
  • Placebos
  • Thiazoles
  • ziprasidone
  • Clozapine
  • Molindone