Association between the use of orexin receptor antagonists and falls or fractures: A meta-analysis

Evidence indicates that the use of sedative-hypnotics, including benzodiazepines and z-drugs, is linked to an increased risk of falls and fractures. Nonetheless, the potential exacerbation of this risk by orexin receptor antagonists, which are novel therapeutic agents for treating insomnia, remains uncertain despite their escalating prevalence in clinical practice. We systematically searched four electronic databases from inception to April 17, 2024. In addition, we performed a quality assessment; calculated pooled odds ratios (ORs) to assess the relationship between the use of orexin receptor antagonists and the occurrence of falls or fractures; evaluated heterogeneity across the included studies; and conducted sensitivity analyses. The meta-analysis encompassed eight papers, comprising a total of 46,636 subjects. These papers included 5 case-control studies and 3 randomized controlled trials (RCTs), collectively encompassing ten studies. Analysis of the included case-control studies (pooled adjusted OR = 0.75, 95% confidence interval [CI] = 0.00-1.50, I² = 66.2%, k = 3) and RCTs (OR = 0.68, 95% CI = 0.31-1.50, I² = 45.9%, k = 5) indicated that the use of orexin receptor antagonists did not elevate the risk of falls. Similarly, analysis of the included case-control studies revealed no significant increase in the risk of fractures associated with the use of orexin receptor antagonists (pooled adjusted OR = 1.01, 95% CI = 0.82-1.20, I² = 40.1%, k = 2). This meta-analysis suggests that the use of orexin receptor antagonists for treating insomnia does not escalate the risk of falls or fractures, although the data for lemborexant and daridorexant are limited.