Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis

Arch Gen Psychiatry. 2011 Jun;68(6):609-16. doi: 10.1001/archgenpsychiatry.2011.2. Epub 2011 Feb 7.


Context: The increased mortality associated with schizophrenia is largely due to cardiovascular disease. Treatment with antipsychotics is associated with weight gain and changes in other cardiovascular risk factors. Early identification of modifiable cardiovascular risk factors is a clinical imperative but prospective longitudinal studies of the early cardiometabolic adverse effects of antipsychotic drug treatment other than weight gain have not been previously reviewed.

Objectives: To assess the methods and reporting of cardiometabolic outcome studies of the first treated episode of psychosis, review key findings, and suggest directions for future research.

Data sources: PsycINFO, MEDLINE, and Scopus from January 1990 to June 2010.

Study selection: Subjects were experiencing their first treated episode of psychosis. Subjects were antipsychotic naive or had been exposed to antipsychotics for a short known period at the beginning of the study. Cardiometabolic indices were assessed. Studies used a longitudinal design.

Data extraction: Sixty-four articles were identified describing 53 independent studies; 25 studies met inclusion criteria and were retained for detailed review.

Data synthesis: Consolidated Standards of Reporting Trials and Strengthening the Reporting of Observational Studies in Epidemiology checklists were used to assess the methods and reporting of studies. A qualitative review of findings was conducted.

Conclusions: Two key hypotheses were identified based on this review: (1) in general, there is no difference in cardiovascular risk assessed by weight or metabolic indices between individuals with an untreated first episode of psychosis and healthy controls and (2) cardiovascular risk increases after first exposure to any antipsychotic drug. A rank order of drugs can be derived but there is no evidence of significant class differences. Recommended directions for future research include assessing the effect on cardiometabolic outcomes of medication adherence and dosage effects, determining the therapeutic window for antipsychotic use in adults and youth, and testing for moderation of outcomes by demographic factors, including sex and age, and clinical and genetic factors.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Dose-Response Relationship, Drug
  • Humans
  • Medication Adherence
  • Psychotic Disorders / complications*
  • Psychotic Disorders / drug therapy*
  • Risk Factors
  • Sex Factors
  • Treatment Outcome
  • Weight Gain / drug effects


  • Antipsychotic Agents