ArticlePLOS mental health2026
The association between new-use of antipsychotics and all-cause mortality in a cohort of patients with dementia in Argentina.
Article in PLOS mental health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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