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Mortality Associated with Conventional vs. Atypical Antipsychotic Drugs

Mortality risks associated with older conventional antipsychotics are comparable to risks of newer antipsychotics in elders.

In April 2005, the FDA issued an advisory stating that atypical antipsychotic drugs can increase the mortality rate in older demented patients with behavior disorders. This advisory, based on an analysis of 17 placebo-controlled studies, motivated researchers to conduct a retrospective cohort study to compare mortality rates among elders who used the newer atypical antipsychotics with those among elders who used older "conventional" antipsychotics.

Using data from a large prescription-benefits program and from Medicare, researchers studied 23,000 patients (age, 65 or older; mean age, 83) who began using a conventional antipsychotic or an atypical antipsychotic (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone) from 1994 to 2003. About half the patients had diagnoses of dementia. During the 6 months after starting the drugs, 17.9% of conventional antipsychotic drug users and 14.6% of atypical antipsychotic drug users died. In analyses adjusting for confounding variables, risk for death was significantly greater with conventional agents than with atypical agents (hazard ratio, 1.37). This increased risk persisted in several confirmatory statistical analyses.

Comment: Although the recent FDA advisory focused on newer atypical antipsychotic agents, the results of this study suggest that mortality risks associated with older conventional antipsychotics are comparable to — and perhaps greater than — risks of newer antipsychotics in elders. However, an editorialist urges that we regard these results with caution, given the potential pitfalls of retrospective observational studies.

— Allan S. Brett, MD

Published in Journal Watch General Medicine December 16, 2005

Citation(s):

Wang PS et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005 Dec 1; 353:2335-41.

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Ray WA. Observational studies of drugs and mortality. N Engl J Med 2005 Dec 1; 353:2319-21.

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• Medline abstract (Free)