Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case-control study

Only three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs.

We identified 84,253 adult individuals who began antipsychotic treatment in a large Italian health care system. Cases were all cohort members who were hospitalized for non-fatal or fatal pulmonary embolism during follow-up. Up to 20 controls for each case were extracted from the study cohort using incidence density sampling and matched by age at cohort entry and gender. Each individual was classified as current, recent or past antipsychotic user. The occurrence non-fatal or fatal pulmonary embolism was the outcome of interest.

Compared to past use, current antipsychotic use more than double the risk of pulmonary embolism (odds ratio 2.31, 95% confidence interval 1.16 to 4.59), while recent use did not increase the risk. Both conventional and atypical antipsychotic exposure was associated with an increase in risk, and the concomitant use of both classes increased the risk of four times (odds ratio 4.21, 95% confidence interval 1.53 to 11.59).

Adding the results of this case-control study to a recent meta-analysis of three observational studies substantially changed the overall estimate, which now indicates that antipsychotic exposure significantly increases the risk of pulmonary embolism.