Bodyweight gain with atypical antipsychotics. A comparative review

Drug Saf. 2001 Jan;24(1):59-73. doi: 10.2165/00002018-200124010-00005.


The atypical antipsychotics have been shown to have superior efficacy compared with typical antipsychotics such as haloperidol, particularly in the treatment of negative symptoms of schizophrenia. Furthermore, they induce less extrapyramidal effects. However, following clinical use, marked bodyweight gain has been frequently observed with some of the atypical antipsychotic drugs. In order to examine and compare the frequency, amount and conditions of bodyweight gain during treatment with atypical antipsychotics, studies concerning bodyweight gain with these agents were identified through a MEDLINE search from 1966 to March 2000. Although comparison is limited by the different designs and recruitment procedures of the reviewed studies, the available data support the notion that the frequency as well as the amount of bodyweight gain is high in patients treated with olanzapine (average bodyweight gain 2.3 kg/month), clozapine (1.7 kg/month), quetiapine (1.8 kg/month), and possibly also zotepine (2.3 kg/month). Moderate changes in bodyweight have been observed in the treatment with risperidone (average bodyweight gain 1.0 kg/month). Ziprasidone seems to induce only slight bodyweight changes (0.8 kg/month). Bodyweight gain most frequently occurs in the first 12 weeks of treatment. Patients who were underweight at the beginning of treatment are at highest risk of gaining bodyweight. The underlying pathomechanism still remains largely unclear. The relative receptor affinities of the atypical antipsychotics for histamine H1 receptors as well as the ratio of their affinity for serotonin 5-HT2 and dopamine D2 receptors appear to be the most robust correlate of bodyweight gain. Furthermore, the induction of leptin secretion may have an important impact on bodyweight gain in patients treated with atypical antipsychotics. Although many questions concerning the pathogenesis of bodyweight gain remain unresolved, this adverse effect has to be taken into consideration when prescribing the atypical antipsychotics, particularly in view its affect on compliance during long term treatment and the long term effects of obesity on mortality and morbidity.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines
  • Clozapine / pharmacology
  • Clozapine / therapeutic use
  • Dibenzothiazepines / pharmacology
  • Dibenzothiazepines / therapeutic use
  • Humans
  • Mental Disorders / drug therapy
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacology
  • Pirenzepine / therapeutic use
  • Quetiapine Fumarate
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / physiology
  • Receptors, Histamine H1 / drug effects
  • Receptors, Histamine H1 / physiology
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Risk Factors
  • Smoking Cessation
  • Weight Gain / drug effects*
  • Weight Gain / physiology


  • Antipsychotic Agents
  • Dibenzothiazepines
  • Receptors, Dopamine D2
  • Receptors, Histamine H1
  • Receptors, Serotonin
  • Benzodiazepines
  • Quetiapine Fumarate
  • Pirenzepine
  • Clozapine
  • Olanzapine