Dual orexin receptor antagonists in insomnia: Toward a new therapeutic paradigm

Although three dual orexin receptor antagonists (DORAs), suvorexant, lemborexant, and daridorexant, are currently available and widely used to treat insomnia, the differences in their elimination half-lives are not sufficient. As a result, clinicians have limited ability to tailor therapy to individual sleep complaints. The emergence of vornorexant, with a notably short half-life comparable to that of zolpidem, may substantially expand the clinical utility of DORAs. This broader spectrum of pharmacokinetic profiles enables more individualized treatment strategies that align with patients' specific sleep complaints. This approach, in turn, potentially reshapes the therapeutic paradigm of insomnia management. However, several challenges remain to be addressed in order to fully realize the clinical potential of DORAs. This review identifies four key challenges requiring resolution to advance their optimal use in clinical practice.