Orexin Receptor Antagonists and Insomnia

Purpose of Review We review recent evidence on the use of orexin receptor antagonists (ORAs) for treating insomnia. We evaluate studies on five dual ORAs and one selective ORA. Recent Findings Research on suvorexant in recent years gradually focus on comorbid insomnia, while lemborexant and daridorexant were still being validated in primary insomnia. Almorexant is now mainly used as a commercial specific inhibitor of the orexin system in animal studies due to safety issues. Although filorexant has also shown a certain sleep-promoting effect, there are few clinical or experimental studies on sleep-related aspects of filorexant in recent years. As for selective ORAs, orexin receptor 2 antagonist seltorexant still has not yet reached phase 3. High-quality clinical trials in insomnia populations are needed which directly compare authorized ORAs and investigate non-approved ORAs, the use of ORAs in comorbid insomnia, and the orexin signaling system pathophysiology in insomnia.

Automated summary

This review examines the use of orexin receptor antagonists (ORAs) in treating insomnia. Recent research focuses on comorbid insomnia with suvorexant, while lemborexant and daridorexant are still being studied for primary insomnia. Almorexant is mainly used in animal studies due to safety concerns. There is limited research on the sleep-promoting effects of filorexant. Seltorexant, a selective ORA, has not reached phase 3 yet. High-quality clinical trials are needed to compare authorized ORAs, investigate non-approved ORAs, and explore the pathophysiology of the orexin signaling system in insomnia.