Mortality in Alzheimer Disease Not Strongly Associated With Antipsychotics

older woman at doctor
older woman at doctor
These results suggest that antipsychotic exposure has no impact on relative mortality.

Data published in the Journal of Clinical Psychiatry indicated that antipsychotic drugs had no impact on relative mortality for patients with Alzheimer disease, but the researchers nevertheless support current guideline recommendations for using only the lowest effective dose of antipsychotic medication during treatment course.

A nationwide retrospective cohort study examined all-cause mortality and antipsychotic exposure in 32,001 Danish patients with Alzheimer disease between 2000 and 2011. Cumulative antipsychotic dosage from diagnosis to end of study was calculated and categorized for each participant according to the World Health Organization Defined Daily Doses.

During the study period, an increasing trend in median survival time was identified in patients; median (95% CI) age at death was 85.26 (85.03-85.57) years for those diagnosed during the 2000 through 2002 interval compared with 90.97 (90.75-91.16) years for those diagnosed during the 2009 through 2011 interval (P <.001).

According to adjusted Cox regression analyses, exposure to antipsychotic drugs was associated with increased mortality; hazard ratios (95% CI) were 2.24 (2.07-2.43) for the 2000 through 2002 period, 2.02 (1.88-2.17) for the 2003 through 2005 period, 1.71 (1.57-1.85) for the 2006 through 2008 period, and 1.24 (1.09-1.41) for the 2009 through 2011 period (all P <.001).

Investigators also found a decline in both antipsychotic exposure and mean annual cumulative Defined Daily Doses across the study period. However, despite an increasing trend in survival time during the study period, no decline was observed in standardized mortality ratios (95% CI), which ranged from 1.19 (0.98-1.46) in 2001 to 1.52 (1.38-1.68) in 2011, suggesting that antipsychotic exposure has no impact on relative mortality. These results also indicate that compared with the general population, patients with Alzheimer disease may have gained less from improvements in the treatment of other conditions that affect mortality rates.

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Researchers acknowledged the limitations of register-based studies, including the potential systematic biases between exposed and unexposed groups, but they underscored the statistical strengths of a large patient population and long follow-up period. They suggested that future studies should explore the differences in treatment between those with and without dementia to discover other factors that affect mortality rates for those with Alzheimer disease.


Nielsen RE, Valentin JB, Lolk A, Andersen K. Effects of antipsychotics on secular mortality trends in patients with Alzheimer’s disease. J Clin Psychiatry. 2018;79(3):17m11595.