Successful Methods for Switching from a Benzodiazepine Receptor Agonist to a Dual Orexin Receptor Antagonist for the Treatment of Insomnias

Objective: Benzodiazepine receptor agonists (BZRAs) are still prescribed for insomnia to many patients in clinical practice, even though dual orexin receptor antagonists (DORAs) are an effective insomnia pharmacotherapy. It is important to establish appropriate methods of switching from BZRAs to DORAs for insomnia treatment. Methods: We performed a secondary analysis of our prior retrospective study of the rate of DORA (suvorexant or lemborexant) continuance at 3 months after the introduction of these agents in 210 patients under long-term BZRA treatment. We investigated the effects of the classes of BZRAs (which are based on half-life lengths) on the DORA continuation rate and the decreased BZRA ratio. Results: Our analyses revealed a significantly lower rate of failure of switching to a DORA in the patients who were being treated with ultra-short/short-acting BZRAs. Two logistic regression analyses of successful switching to DORAs identified the following as predictors of a 3-month continuation of a DORA: (i) a higher-dose BZRA at baseline (Exp(B): 1.570, 95% CI: 1.090−2.262), (ii) shorter-term BZRA use (Exp(B): 0.991, 95% CI: 0.985−0.997), and (iii) BZRA with ultra-short/short half-lives (Exp(B): 7.335, 95% CI: 2.054−26.188). The analyses identified higher BZRA dose at baseline (Exp(B): 1.801, 95% CI: 1.008−3.216) as a predictor of both DORA continuation and BZRA tapering. Conclusion: These findings suggest that in efforts to switch a patient’s insomnia medication to a DORA, the tapering of ultra-short/short-acting BZRAs can lead to the successful switch to a DORA among patients under high-dose BZRA treatment, whereas careful switching is necessary for patients under long-term BZRA treatment.