Antipsychotics appear to be associated with increased risk of death in elderly

A new Institute for Clinical Evaluative Sciences (ICES) study shows that the use of newer atypical antipsychotics appears to be associated with an increased risk of death in older Ontarians with dementia, and older antipsychotic drugs (also known as conventional or typical antipsychotics) may pose an even greater risk of death than the atypicals.

“Both the United States Food and Drug Administration and Health Canada issued warnings in 2005 that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk of death. Recent studies have provided support for these warnings and have raised further safety concerns about the older typical antipsychotics,” said Dr. Sudeep Gill, ICES adjunct scientist.

“Previous trials have generally been very short and could not provide information about the long-term impact of antipsychotics on mortality. As well, relatively little information is available on the harms associated with older typical antipsychotics.”

To examine this issue further, investigators tracked all Ontario residents 66 years of age and older with dementia between April 1997 and March 2003. The risk of death was determined at 30, 60, 120 and 180 days following the initial use of either typical or atypical antipsychotics in seniors who lived in the community, as well as those who lived in long-term care facilities. The risk of death was compared for atypical versus no antipsychotic use, and typical versus atypical antipsychotic use.

New use of atypical antipsychotic medications was associated with an increased risk of death at 30 days, relative to no antipsychotics use in both community-dwelling seniors and long-term care residents. This risk appeared to persist to 180 days in both groups. At 180 days, mortality was 9% among atypical antipsychotic users and 8% among non-users in the community-dwelling group. In long-term care residents, mortality at 180 days was 17% among atypical antipsychotic users and 15% among non-users.

The use of typical antipsychotics was associated with an even greater risk of death than the use of atypical antipsychotics. This risk was evident at 30 days and again appeared to persist to 180 days. In the community-dwelling group, mortality at 180 days was 13% among typical antipsychotic users and 11% among atypical antipsychotic users. In the long-term care residents, mortality at 180 days was 20% among typical antipsychotic users and 18% among atypical antipsychotic users.

“Although these numbers may at first not appear that dramatic, the severity of the outcome and the relatively short follow-up time of 30 days to six months means that even increases of one or two per cent are highly significant and clinically important, especially when considering that for many elderly dementia patients these medications may not be very beneficial,” said Dr. Gill.

“Clinicians should frequently re-evaluate the benefits and risks of antipsychotic therapy for their elderly dementia patients and consider discontinuation of treatment when appropriate.”

Dr. Gill also stresses that “antipsychotics should not be initiated if effective non-drug treatments are available or symptoms are unlikely to respond to antipsychotic treatment. Clinical trials involving behaviour management and caregiver education have shown benefits in both community-dwelling seniors and long-term care residents, and may help to minimize antipsychotic use. Efforts are needed to facilitate the implementation of these effective interventions into clinical practice.”

The study, “Antipsychotic drug use and mortality among older adults with dementia”, is in the June 5, 2007 issue of the Annals of Internal Medicine.

Author affiliations: ICES (Drs. Gill, Bronskill, Anderson, Bell, Fischer and Rochon, Ms. Sykora and Mr. Lam); Department of Medicine, Queen’s University (Dr. Gill); Harvard Medical School and Harvard School of Public Health (Dr. Normand); Departments of Medicine (Drs. Bell and Rochon) and Psychiatry (Dr. Herrmann), University of Toronto; Department of Medicine, University of British Columbia (Dr. Lee); Meyers Primary Care Institute of the University of Massachusetts Medical School, the Fallon Clinic Foundation, and the Fallon Community Health Plan (Dr. Gurwitz); Baycrest Geriatric Healthcare System (Dr. Rochon).

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of healthcare issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting healthcare needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy.

This study was supported by the Canadian Institutes of Health Research (CIHR). 

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