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Previous Volume 353:2335-2341 December 1, 2005 Number 22 Next

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ABSTRACT

Background Recently, the Food and Drug Administration (FDA) issued an advisory stating that atypical antipsychotic medications increase mortality among elderly patients. However, the advisory did not apply to conventional antipsychotic medications; the risk of death with these older agents is not known.

Methods We conducted a retrospective cohort study involving 22,890 patients 65 years of age or older who had drug insurance benefits in Pennsylvania and who began receiving a conventional or atypical antipsychotic medication between 1994 and 2003. Analyses of mortality rates and Cox proportional-hazards models were used to compare the risk of death within 180 days, less than 40 days, 40 to 79 days, and 80 to 180 days after the initiation of therapy with an antipsychotic medication. We controlled for potential confounding variables with the use of traditional multivariate Cox models, propensity-score adjustments, and an instrumental-variable analysis.

Results Conventional antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied (180 days: relative risk, 1.37; 95 percent confidence interval, 1.27 to 1.49; <40 days: relative risk, 1.56; 95 percent confidence interval, 1.37 to 1.78; 40 to 79 days: relative risk, 1.37; 95 percent confidence interval, 1.19 to 1.59; and 80 to 180 days: relative risk, 1.27; 95 percent confidence interval, 1.14 to 1.41) and in all subgroups defined according to the presence or absence of dementia or nursing home residency. The greatest increases in risk occurred soon after therapy was initiated and with higher dosages of conventional antipsychotic medications. Increased risks associated with conventional as compared with atypical antipsychotic medications persisted in confirmatory analyses performed with the use of propensity-score adjustment and instrumental-variable estimation.

Conclusions If confirmed, these results suggest that conventional antipsychotic medications are at least as likely as atypical agents to increase the risk of death among elderly persons and that conventional drugs should not be used to replace atypical agents discontinued in response to the FDA warning.

Source Information

From the Department of Psychiatry (P.S.W.) and the Division of Pharmacoepidemiology and Pharmacoeconomics (P.S.W., S.S., J.A., M.A.F., H.M., D.H.S., M.A.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.

Address reprint requests to Dr. Wang at the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 1620 Tremont St., Suite 3030, Boston, MA 02120, or at pwang{at}rics.bwh.harvard.edu.

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Related Letters:

Conventional vs. Atypical Antipsychotic Medications
Lee S. J., Newman T. B., Barbui C., Cipriani A., Tansella M., Stone M., Racoosin J. A., Laughren T., Kruszewski S. P., Klotz S. G., Wang P. S., Schneeweiss S., Brookhart M. A.
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N Engl J Med 2006; 354:972-974, Mar 2, 2006. Correspondence

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