Supplementary Material for: All-cause mortality associated with antipsychotic use in people living with dementia and neuropsychiatric symptoms: secondary analysis of a systematic review and meta-analysis

ABSTRACT Objectives: 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., 2025, Am J Geriatr Psychiatry).” Keywords: dementia, neuropsychiatric symptoms, antipsychotics, mortality