Effects of Antipsychotics on Secular Mortality Trends in Patients With Alzheimer’s Disease

Objective: To investigate secular changes in mortality rates between patients with Alzheimer’s disease (AD) and the general population as well as changes in antipsychotic drug treatment and the association between drug treatment and mortality in patients with AD in Denmark during a 12-year study period.

Methods: This nationwide, retrospective cohort study identified all-cause mortality in all Danish patients with incident ICD-10-defined AD from 2000 through 2011. The cumulative antipsychotic dosages from dementia diagnosis until end of study for each participant were calculated and categorized in 1 of 5 groups per the World Health Organization Defined Daily Doses (DDDs). Data were obtained from relevant Danish national registers.

Results: The study included 32,001 patients (11,194 male and 20,807 female). During the study period, an increasing trend was found in median survival time, but no decline was seen in standardized mortality ratios, which spanned from 1.19 (95% CI, 0.98-1.46) in 2001 to 1.52 (95% CI, 1.38-1.68) in 2011. The findings showed a decline in proportion of patients with incident AD exposed to antipsychotic drugs as well as decline in mean annual cumulative DDDs. Adjusted Cox regression analyses revealed that current exposure to antipsychotic drugs was associated with increased mortality, although hazard ratios declined during the study period from 2.24 (95% CI, 2.07-2.43) in 2000-2002 to 1.24 (95% CI, 1.09-1.41) in 2009-2011, with P values < .001.

Conclusions: These findings appear to underscore the current guideline recommendations for using antipsychotic drugs at only the lowest effective dose and only in patients for whom all non-pharmacologic options have been exhausted. Furthermore, these results seem to indicate that the reduced use of antipsychotic drugs has no impact on relative mortality, suggesting that the AD population has gained less from improvements in care of other diseases that impact mortality rates in patients with AD as well as in the general population.