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Antipsychotic Drugs and Sudden Cardiac Death

Both typical and atypical agents doubled risk for sudden cardiac death.

The latest evidence linking antipsychotic drugs to sudden cardiac death is provided by a retrospective cohort study based on data from Tennessee Medicaid. Vanderbilt University researchers identified 93,000 adults (age range, 30–74) who used antipsychotic drugs between 1990 and 2005; about half used typical agents (most commonly haloperidol or thioridazine), and half used atypical agents (most commonly clozapine, quetiapine, olanzapine, or risperidone). These patients were matched by age and sex with 186,000 controls.

The rate of sudden cardiac death was twofold higher among current users of antipsychotic drugs than among nonusers (about 29 vs. 14 sudden deaths per 10,000 person-years). This significant doubling of risk was noted with both typical and atypical agents. These findings were strengthened by several additional analyses: A dose-response pattern was noted; risk for former (i.e., noncurrent) antipsychotic drug users was similar to that of nonusers; and findings from a propensity analysis (which minimizes the influence of potentially confounding factors) mirrored those of the initial analysis.

Comment: This study provides additional evidence that both typical and atypical antipsychotic drugs elevate risk for sudden cardiac death. A plausible mechanism exists: Antipsychotic drugs block repolarizing potassium currents and can prolong the QT interval. In a strongly worded editorial, the writers advocate sharp reductions in use of these agents for off-label indications (e.g., behavior control in dementia patients) and suggest that patients undergo electrocardiography before and shortly after starting these drugs (to detect QT prolongation).

— Allan S. Brett, MD

Published in Journal Watch General Medicine January 14, 2009

Citation(s):

Ray WA et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009 Jan 15; 360:225.

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Schneeweiss S and Avorn J. Antipsychotic agents and sudden cardiac death — How should we manage the risk? N Engl J Med 2009 Jan 15; 360:294.

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• Medline abstract (Free)