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Contrary to General Warnings, All Antipsychotics May Not Increase Short-Term Risk for Mortality among Veterans with Dementia


There are no FDA-approved treatments for the behavioral symptoms of dementia; however, antipsychotic medications are widely prescribed for this indication. In 2005, the FDA issued a boxed warning about an increased risk of mortality associated with the use of atypical antipsychotic medications in patients with dementia, which was expanded to include conventional antipsychotics in 2008. This five-year retrospective study sought to estimate mortality risk associated with antipsychotics commonly prescribed for patients with dementia. Investigators identified Veterans, 65 years and older, who had an inpatient or outpatient VA healthcare record that listed a diagnosis of dementia from 10/99 to 9/05. Veterans who received antipsychotic therapy were compared to randomly-selected Veterans with a diagnosis of dementia who had not received antipsychotic therapy. Veterans who received antipsychotic therapy were divided into four cohorts according to drug prescription: haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277) and risperidone (n=8,249). Covariates included comorbidities, demographics, and medication history.

Findings show that commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with short-term increases in mortality. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily low dose of haloperidol, olanzapine, or risperidone, after adjusting for demographics, comorbidities, and medication history. However, increased mortality was not seen when quetiapine was prescribed. No antipsychotic was associated with increased mortality after the first 30 days. Therefore, the authors suggest that all antipsychotics might not pose the same degree of risk in all patient groups as implied by the general warnings that have been issued. Further research is needed to determine whether or under what circumstances each antipsychotic poses less or even no mortality risk.

PubMed Logo Rossom R, Rector T, Lederle F, and Dysken M. Are all commonly prescribed antipsychotics associated with increased mortality in elderly male Veterans with dementia? Journal of the American Geriatrics Society May 7, 2010;e-pub ahead of print.

This study was partly funded by HSR&D. Drs. Rector and Lederle are part of HSR&D's Center for Chronic Disease Outcomes Research in Minneapolis, MN.

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HSR&D requires notification by HSR&D-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR&D and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR&D based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR&D published articles. Visit the HSR&D citations database for a complete listing of HSR&D articles and presentations.