Risk of falls and delirium associated with dual orexin receptor antagonists versus benzodiazepines and Z-drugs in older adults with dementia

Insomnia in older adults with dementia is commonly treated with benzodiazepines (BZDs) and Z drugs, despite safety concerns. Evidence on dual orexin receptor antagonists (DORAs) in this population remains limited. Therefore, this study aimed to compare safety outcomes of DORAs versus BZDs/Z drugs in older adults with dementia and insomnia. This retrospective observational cohort study used electronic health records from TriNetX Global Collaborative Network. From 17,226 eligible adults aged ≥65 years with dementia and insomnia, 734 matched pairs were included after propensity score matching. Participants received DORAs (suvorexant, lemborexant, or daridorexant) or BZDs/Z drugs within 1 month of dementia diagnosis. Primary outcomes were falls and delirium over 12 months. Secondary outcomes included hospitalization, mortality, and emergency department visits. Among 734 matched pairs (mean age 83.5 years; 65-66% female), DORA use was associated with significantly lower risk of falls (HR 0.35, 95% CI 0.18-0.71; P = 0.003), delirium (HR 0.39, 95% CI 0.23-0.65; P < 0.001), hospitalization (HR 0.31, 95% CI 0.21-0.47; P < 0.001), and emergency department visits (HR 0.32, 95% CI 0.20-0.50; P < 0.001). No significant difference in mortality was observed (HR 0.77, 95% CI 0.53-1.11; P = 0.154). In conclusion, DORA was associated with substantially lower risks of falls, delirium, hospitalization, and emergency visits compared with BZDs/Z drugs in older adults with dementia. DORAs may offer a safer alternative to BZDs/Z drugs for managing insomnia in older adults with dementia, potentially reducing fall-related injuries and healthcare utilization.