The association between new-use of antipsychotics and all-cause mortality in a cohort of patients with dementia in Argentina

Multiple studies have associated antipsychotic use with increased mortality among individuals with dementia, but evidence in Latin America remains limited. We conducted a retrospective cohort study among outpatients aged 60 years and older receiving care within a large health maintenance organization in Argentina. Participants underwent cognitive evaluation resulting in dementia diagnosis between January 2017 and December 2021. The main exposure was the new-use of antipsychotics after dementia diagnosis. We fitted multivariable Cox proportional hazards models for the association between new-use of antipsychotics and all-cause mortality to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI), adjusted for demographics, behavioral factors, and comorbidities. To evaluate dose-response patterns, we used standardized daily doses of antipsychotics (SDD) measured every three months and modelled using restricted cubic splines. Overall, we included 1,326 patients ≥60 years with a new dementia diagnosis, of whom 325 (25%) started antipsychotic treatment during follow-up. Median follow-up time in the entire cohort was 963 (interquartile range: 452–1,333) days and 184/1,326 (14%) of patients died during follow-up. Overall, female sex was most prevalent, and a quarter of patients had completed their secondary education. New-users of antipsychotics had a higher hazard of all-cause mortality compared with non-users (aHR = 2.66, 95%CI: 1.93, 3.67), after adjusting for potential confounders. In secondary analyses, we found no evidence of higher mortality with increasing cumulative antipsychotic exposure. Compared with non-use, the aHRs were inconsistent across cumulative dose levels: 30 SDD (aHR = 2.51, 95%CI: 1.69, 3.74), 90 SDD (aHR = 3.88, 95%CI: 2.30, 6.53), and 365 SDD (aHR = 2.20, 95%CI: 1.22, 3.96). In conclusion, in this retrospective cohort with predominantly female participants with low educational attainment in Argentina, new-use of antipsychotics was associated with higher risk of all-cause mortality among patients with dementia. These findings highlight the importance of minimizing the use of antipsychotics in patients with dementia when feasible.