Orexin Receptor Antagonists and Insomnia

Curr Psychiatry Rep. 2022 Oct;24(10):509-521. doi: 10.1007/s11920-022-01357-w. Epub 2022 Aug 16.

Abstract

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.

Keywords: Daridorexant; Insomnia; Lemborexant; Orexin receptor antagonists; Orexin system; Suvorexant.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Orexin Receptor Antagonists* / pharmacology
  • Orexin Receptor Antagonists* / therapeutic use
  • Orexin Receptors
  • Orexins / pharmacology
  • Sleep / physiology
  • Sleep Initiation and Maintenance Disorders* / drug therapy

Substances

  • Orexin Receptor Antagonists
  • Orexin Receptors
  • Orexins