Increase in sudden cardiac death

Antipsychotics, both typical and atypical, are associated with a dose-related increase in sudden cardiac death according to a new study. Typical antipsychotics such as thioridazine (Mellaril®) and haloperidol (Haldol®) block repolarizing potassium currents and prolong QT intervals. Multiple studies have shown a dose-related increased risk of sudden cardiac death associated with these drugs. Less is known about the atypical antipsychotic drugs although many have similar cardiovascular effects. Researchers from Nashville reviewed the records of Medicaid enrollees in Tennessee including the records of 44,218 and 46,089 baseline users of a single typical and atypical antipsychotic, respectively. These were matched with 186,600 nonusers of antipsychotic drugs. Thioridazine and haloperidol were the most frequently prescribed typical agents, while clozapine (Clozaril®), quetiapine (Seroquel®), olanzapine (Zyprexa®), and risperidone (Risperdal®) were the most commonly used atypical agents. Both users of typical and atypical antipsychotic drugs had higher rates of sudden cardiac death than nonusers with adjusted incident rate ratios of 1.99 (95% CI, 1.68-2.34) and 2.26 (95% CI, 1.8-2.72), respectively. There was a higher rate for users of atypical antipsychotic drugs vs typical antipsychotics with an incident rate of 1.14 for the comparison (95% CI, 0.93-1.39). For both classes of drugs, the risk for current users increased significantly with increasing dose. The authors conclude that current users of typical and of atypical antipsychotic drugs had similar, dose-related increased risk of sudden cardiac death and that atypical antipsychotic drugs are no safer than the older drugs (Ray WA, et al. N Engl J Med 2009;360:225-235). An accompanying editorial suggests that children and the elderly are particularly vulnerable to these drugs and their use in these populations should be "sharply reduced" (Schneeweiss S, Avorn J. N Engl J Med 2009;360:294-296).