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Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients

From the Division of Pharmacoepidemiology and Pharmacoeconomics (Schneeweiss, Setoguchi, Wang, Brookhart), Department of Medicine, and the Department of Psychiatry (Wang), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.; the Therapeutics Initiative (Dormuth), Department of Anesthesia, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC; and the Division of Services and Intervention Research (Wang), National Institute of Mental Health, Bethesda, Md.

Correspondence to: Dr. Sebastian Schneeweiss, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, 1620 Tremont St., Boston MA 021205, USA; fax 617 232-8602; schneeweiss{at}post.harvard.edu

Background: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the short-term mortality in a population-based cohort of elderly people in British Columbia who were prescribed conventional and atypical antipsychotic medications.

Methods: We used linked health care utilization data of all BC residents to identify a cohort of people aged 65 years and older who began taking antipsychotic medications between January 1996 and December 2004 and were free of cancer. We compared the 180-day all-cause mortality between residents taking conventional antipsychotic medications and those taking atypical antipsychotic medications.

Results: Of 37 241 elderly people in the study cohort, 12 882 were prescribed a conventional antipsychotic medication and 24 359 an atypical formulation. Within the first 180 days of use, 1822 patients (14.1%) in the conventional drug group died, compared with 2337 (9.6%) in the atypical drug group (mortality ratio 1.47, 95% confidence interval [CI] 1.39–1.56). Multivariable adjustment resulted in a 180-day mortality ratio of 1.32 (1.23–1.42). In comparison with risperidone, haloperidol was associated with the greatest increase in mortality (mortality ratio 2.14, 95% CI 1.86–2.45) and loxapine the lowest (mortality ratio 1.29, 95% CI 1.19–1.40). The greatest increase in mortality occurred among people taking higher (above median) doses of conventional antipsychotic medications (mortality ratio 1.67, 95% CI 1.50–1.86) and during the first 40 days after the start of drug therapy (mortality ratio 1.60, 95% CI 1.42–1.80). Results were confirmed in propensity score analyses and instrumental variable estimation, minimizing residual confounding.

Interpretation: Among elderly patients, the risk of death associated with conventional antipsychotic medications is comparable to and possibly greater than the risk of death associated with atypical antipsychotic medications. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients.

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