An update on dual orexin receptor antagonists and their potential role in insomnia therapeutics

Study Objectives: Current pharmacological options for the treatment of insomnia insufficiently meet the needs of all insomnia patients. Approved treatments are not consistently effective in improving sleep onset and sleep maintenance, while also having complicated safety profiles. These limitations highlight the unmet need for additional medications and treatment strategies. Initial research suggests that the dual orexin receptor antagonists (DORAs) may offer an additional pharmaceutical option to treat insomnia in some patients. Methods: We reviewed the existing literature on dual orexin receptor antagonists in PubMed databases using the search terms “orexin receptor antagonist,” “almorexant” “filorexant,” “lembroexant” and “suvorexant”; searches were limited to English language primary research articles, clinical trials, and reviews. Results: Targeting the orexin receptor system for treatment of insomnia offers an additional and alternative pharmacological approach to more common gamma aminobutyric acid agonist sedative hypnotic treatment. Effectiveness is not well established in the current literature; however, the literature does suggest efficacy. Preclinical reports also suggest the potential for treatment in individuals with comorbid Alzheimer disease and insomnia. Conclusions: DORAs offer an additional treatment option for insomnia. More clinical trials are needed to robustly evaluate their safety and effectiveness in several subclasses of individuals with insomnia. Given the published literature, head-to-head comparisons to existing treatment for insomnia are warranted.