Antipsychotic Drug Use and Mortality in Older Adults with Dementia

BACKGROUND: Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety. OBJECTIVE: To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality. DESIGN: Population-based, retrospective cohort study. SETTING: Ontario, Canada. PATIENTS: Older adults with dementia who were followed between 1 April 1997 and 31 March 2003. MEASUREMENTS: The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status. RESULTS: A total of 27,259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 95% CI, 1.02 to 1.70; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 CI, 1.15 to 2.07; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations. LIMITATIONS: Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations. CONCLUSIONS: Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.