Antipsychotics and the Risk of Sudden Cardiac Death

Abstract

In developed countries, sudden cardiac death is one of the major causes of cardiovascular mortality. According to the most recent definition, sudden cardiac death is a natural death due to cardiac causes, heralded by abrupt loss of consciousness within 1 hour after the onset of acute symptoms or an unwitnessed, unexpected death of someone seen in a stable medical condition less than 24 hours previously with no evidence of a noncardiac cause.^1,2 Since the early 1960s, sudden cardiac death has been reported with antipsychotic use in case reports.^3-5 Although the precise mechanism remains uncertain, several have been suggested including peripheral vasodilatation leading to cardiovascular collapse, oral laryngeal-pharyngeal dystonia, acute myocarditis, and cardiomyopathy.⁶ Particular attention has been paid to the ability of antipsychotics to prolong the corrected QT (QTc) interval, which may result in torsades de pointes and other cardiac arrhythmias.^6-8 Only a few epidemiological studies have addressed the issue of sudden cardiac death and antipsychotic use, finding an increased risk of sudden cardiac death with the use of antipsychotics, varying from 1.7 (rate ratio) to 5.3 (odds ratio).^8-10 These studies, however, were either small and performed in hospitalized psychiatric patients or were performed in administrative databases with little information on potential confounders. Moreover, because of the inability to validate the diagnosis of sudden cardiac death in medical records, most of these studies may have misclassified the outcome.