Antipsychotic drug exposure and risk of venous thromboembolism: a systematic review and meta-analysis of observational studies.

backgroundVenous thromboembolism (VTE) is a serious disorder that may be complicated by pulmonary embolism (PE). Case reports and observational studies published in the early 1950s suggested that antipsychotic (AP) drugs may represent a risk factor, while observational studies conducted in the last 3 decades have provided conflicting results.

objectiveThe aim was to investigate whether AP drugs increase the risk of VTE and PE, and to ascertain the risk associated with first- and second-generation AP drugs and with exposure to individual drugs. DATA SOURCE: Relevant studies were located by searching MEDLINE, PubMed, EMBASE, PsychINFO, CINAHL and Scopus up to March 2013. Reference lists of relevant papers and previous review articles were hand searched for other relevant studies. STUDY SELECTION: Based on the titles and abstracts of 1,386 citations, we identified 30 potentially relevant studies. Of these, 17 studies were eligible for inclusion and were included in the meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome measure of this meta-analysis was the occurrence of VTE or PE in individuals exposed to AP drugs in comparison with individuals unexposed or with past exposure to AP drugs.

resultsAntipsychotic exposure was associated with a significant increase in risk of developing VTE [odds ratio (OR) 1.54, 95% confidence interval (CI) 1.28-1.86, 11 studies]. Exposure to APs did not significantly increase the risk of PE (OR 4.90, 95% CI 0.77-30.98, three studies), but the overall estimate was highly heterogeneous and the CI included the possibility of substantial harm. Random-effects meta-analysis on the risk of VTE associated with exposure to first- (OR 1.74, 95% CI 1.28-2.37, six studies) and second-generation (OR 2.07, 95% CI 1.74-2.52, five studies) APs revealed an increased risk. Only a few studies provided data on individual drugs, and estimates of effect were very uncertain.

conclusionsAntipsychotic exposure in unselected patient populations may be associated with a 50% increase in the risk of developing VTE. However, between-study heterogeneity limits the confidence in this estimate. This increased risk similarly applies to first- and second-generation AP drugs.