Dual orexin receptor antagonist-assisted dose reduction of benzodiazepines and benzodiazepine receptor agonists: a mirror-image analysis of insurance claims data.

PURPOSE: Discontinuing benzodiazepines and benzodiazepine receptor agonists (BZ/BZRAs) remains challenging for patients with chronic insomnia despite safety concerns. This study evaluated whether continuous treatment with dual orexin receptor antagonists (DORAs) facilitates a reduction in BZ/BZRA doses among long-term users.

METHODS

This self-controlled (mirror-image) study, in which each patient served as their own control, used Japanese health insurance claims data (Dokenpo database, 2019-2024). Eligible patients had continuous BZ/BZRA use for ≥ 6 months and initiated suvorexant or lemborexant for ≥ 6 months. Changes in bedtime BZ/BZRA dose (diazepam equivalents) were compared between pre- and post-DORA periods. Logistic regression analyses identified factors associated with ≥ 50% dose reduction and BZ/BZRA discontinuation.

RESULTS

Prior to DORA initiation, 605 patients were taking a mean of 1.9 ± 1.0 types of BZ/BZRAs at a pretreatment total daily dose of 8.2 ± 7.4 mg diazepam equivalent. Of these, 42.1% achieved ≥ 50% bedtime BZ/BZRA dose reduction and 21.3% achieved discontinuation. Mean bedtime doses decreased in both the suvorexant group (7.2 to 5.2 mg) and the lemborexant group (8.3 to 5.2 mg). In adjusted analyses, age ≥ 65 years was independently associated with both ≥ 50% reduction (odds ratio [OR] 2.485; 95% confidence interval [CI] 1.190-5.192; p = 0.015) and discontinuation (OR 2.636; 95% CI 1.158-6.000; p = 0.021). Lower pretreatment BZ/BZRA dose and lemborexant use were also associated with dose reduction and discontinuation.

CONCLUSION

DORA treatment for at least six months may support BZ/BZRA dose reduction among long-term users, particularly in older patients.

CURRENT KNOWLEDGE/STUDY RATIONALE: Discontinuing benzodiazepine and benzodiazepine receptor agonists (BZ/BZRAs) in patients with long-term use remains clinically challenging despite well-documented safety concerns. Whether sustained treatment with dual orexin receptor antagonists (DORAs) facilitates BZ/BZRA dose reduction in real-world practice has not been adequately examined in patients already exposed for six months or longer.

STUDY IMPACT: Sustained DORA treatment for at least six months was associated with substantial bedtime BZ/BZRA dose reduction and discontinuation among long-term users, with older adults (aged 65 years or older) showing the highest odds of success. These findings support DORA co-administration as a practical pharmacological switching strategy to enable safer insomnia management, particularly in populations vulnerable to BZ/BZRA-related adverse events.