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Use of Dual Orexin Receptor Antagonists for Insomnia and the Risk of Falls and Fractures: A Systematic Review and
Arianna Paolone1, Shehraz Riar2, Shajjan Vejayavarnan3
1Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Background:
Falls are the leading cause of injury in older adults. Sedative-hypnotic use is a known risk factor, but their use for insomnia continues to be common. Dual orexin receptor antagonists (DORAs) are a new, potentially safer class of medications for insomnia. We conducted a systematic review and meta-analysis to assess the effect of DORAs on falls and fractures.
Methods:
We searched MEDLINE, EMBASE, and CENTRAL from inception to August 2025 for studies reporting falls and fractures in DORA users and non-users. Randomized controlled trials (RCTs) or observational studies that reported data on falls and/or fractures for participants using DORAs in any clinical setting were included. Citation screening, full-text review, and data abstraction were conducted in duplicate. Random-effects model meta-analyses were conducted. The primary outcomes were the incidence or rates of falls and fractures among adults using DORAs compared to non-users. We also calculated the optimal information size (OIS), which is the minimum number of events needed to detect a clinically meaningful effect.
Results:
Nineteen studies (10 RCTs, 9 observational, 183,595 participants) met inclusion criteria. Across all studies, DORA use did not increase the risk of falls compared to non-use (OR 0.76, 95% CI 0.56-1.04). RCT data suggest a reduction in fall risk (OR 0.59, 95% CI 0.35-0.98) not seen in observational studies (OR 0.88, 95% CI 0.59-1.31). No association was observed between DORAs and fractures (OR 1.05, 95% CI 0.94-1.18).
Conclusions:
DORAs do not appear to increase the risk of falls or fractures in adults. Although these findings suggest that DORAs may be safer alternatives to traditional insomnia agents, low event rates, failure to meet the OIS, and limited data in older adults warrant cautious interpretation. Further research is needed to validate these findings and better characterize the relationship between DORAs and falls and fractures, particularly in older adults.
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