Antipsychotic Use and Mortality Risk in Community-Dwelling Alzheimer’s Disease Patients: Evidence for a Role of Dementia Severity

Antipsychotics are widely used for the treatment of behavioral and psychological symptoms of dementia (BPSD). Concerns have been raised in the literature over the safety of antipsychotics, with suggestions of an increased risk of mortality. The objective of this study was to determine the all-cause mortality risk associated with antipsychotic use among Alzheimer’s disease (AD) patients. A new-user study was conducted in a multicentric prospective cohort, composed of 534 community-dwelling mild-to-moderate AD patients recruited in 16 French memory centers. A survival analysis using a Cox proportional hazards model assessed hazard ratios (HRs) for death according to either first or second generation antipsychotic use (time-varying variable). Among the 534 patients, 102 new users were identified throughout the 3.5 year-follow-up period and 113 deaths occurred. The main antipsychotics used were risperidone and tiapride. Unadjusted and sociodemographic-adjusted (age, gender, center) analyses suggested an increased risk of death with antipsychotic use (HR: 1.84; 95% CI: [1.09-3.09] and HR: 1.93; 95% CI: [1.15-3.25]) respectively). However, antipsychotic use did not appear to be an independent predictive factor of death when dementia severity (cognitive status) was accounted for during fully adjusted multivariate analyses (HR: 1.12; 95% CI: [0.59-2.12]). Antipsychotic use may be associated with an increased risk of mortality, but to a lesser extent than several other factors which were found to be significant predictors of mortality (age, male gender, cognitive score, recent hospitalisation, medical aid). To date, antipsychotic risks outweigh their benefits in BPSD for which non-pharmacological approaches remain the first-line strategy and should be privileged.