All-Cause Mortality Associated with Antipsychotic Use in People Living with Dementia and Neuropsychiatric Symptoms: Secondary Analysis of a Systematic Review and Meta-Analysis

INTRODUCTION: Neuropsychiatric symptoms (NPS) are highly prevalent in dementia and represent a major driver of functional decline, caregiver burden, and mortality. When symptoms become severe or refractory to non-pharmacological measures, antipsychotics are frequently introduced despite ongoing safety concerns. Their impact on survival in community-dwelling patients with NPS, however, remains uncertain. This study aimed to examine the association between antipsychotic use and all-cause mortality in older adults with dementia and NPS. METHODS: This analysis was registered in PROSPERO (CRD42024621462), conducted in accordance with the Cochrane Handbook, and reported following PRISMA 2020 guidelines. Eligible observational studies included community-dwelling adults aged ≥65 years with dementia and documented NPS, reporting adjusted hazard ratios (aHRs) for antipsychotic use and all-cause mortality. Pooled estimates were derived using fixed-effects models. RESULTS: Five observational cohort studies including 14,183 participants were analyzed. Antipsychotic use was not significantly associated with all-cause mortality (pooled aHR = 1.06; 95% CI: 0.97-1.16; p = 0.21; I2 = 43%). Subgroup analyses showed aHR = 0.79 (95% CI: 0.62-1.01) for typical antipsychotics and aHR = 1.23 (95% CI: 0.97-1.56) for atypical agents, with a significant difference between classes (p = 0.03). CONCLUSIONS: In community-dwelling older adults with dementia and NPS, no statistically significant association between antipsychotic use and all-cause mortality was observed. However, the available evidence is limited and imprecise, resulting in substantial uncertainty. These findings should therefore be interpreted with caution. This study is a secondary analysis of a previously published systematic review and meta-analysis [O'Hara-Veintimilla et al. Am J Geriatr Psychiatry. 2025;23(25):S1064-7481].