Antipsychotics and the risk of sudden cardiac death

Background: Case reports link antipsychotic drugs with sudden cardiac death s, which is consistent with dose-related electrophysiologic effects. Becaus e this association has not been confirmed in controlled studies, we conduct ed a retrospective cohort study in Tennessee Medicaid enrollees, which incl uded many antipsychotic users; there were also computer files describing me dication use and comorbidity. The study was conducted before the introducti on of risperidone and, thus, did not include the newer atypical agents. Methods: The cohort included 481744 persons with 1282996 person-years of fo llow-up. This included 26749 person-years for current moderate-dose antipsy chotic use (> 100-mg thioridazine equivalents), 31864 person-years for curr ent low-dose antipsychotic use, 37881 person-years for use in the past year only, and 1186501 person-years for no use. The cohort had 1487 confirmed s udden cardiac deaths; from these, we calculated multivariate rate ratios ad justed for potential confounding factors. Results: When current moderate-dose antipsychotic use was compared with non use, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3. 22; P < .001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P=.003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P < .001) use. Among cohort membe rs with severe cardiovascular disease, current moderate-dose users had a 3. 53-fold (95% confidence interval, 1.66-7.51) increased rate relative to com parable nonusers (P < .001), resulting in 367 additional deaths per 10000 p erson-years of follow-up. Conclusions: Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Altho ugh the study data cannot demonstrate causality, they suggest that the pote ntial adverse cardiac effects of antipsychotics should be considered in cli nical practice, particularly for patients with cardiovascular disease.