Efficacy of orexin antagonists for the management of major depressive disorder: A systematic review of randomized clinical trials

Shakila Meshkat; Angela T H Kwan; Gia Han Le; Sabrina Wong; Kayla M Teopiz; Larry Wang; Joshua D Rosenblat; Taeho Greg Rhee; Bing Cao; Roger S McIntyre

doi:10.1016/j.jad.2024.12.008

Efficacy of orexin antagonists for the management of major depressive disorder: A systematic review of randomized clinical trials

J Affect Disord. 2024 Dec 4:372:409-419. doi: 10.1016/j.jad.2024.12.008. Online ahead of print.

Authors

Shakila Meshkat¹, Angela T H Kwan², Gia Han Le³, Sabrina Wong⁴, Kayla M Teopiz⁵, Larry Wang⁶, Joshua D Rosenblat⁷, Taeho Greg Rhee⁸, Bing Cao⁹, Roger S McIntyre¹⁰

Affiliations

¹ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
² Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
³ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁴ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
⁵ Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
⁶ Department of Psychiatry, Central Michigan University, Saginaw, MI, USA.
⁷ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, CT, USA.
⁹ Key Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing 400715, PR China.
¹⁰ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: [email protected].

PMID: 39638064
DOI: 10.1016/j.jad.2024.12.008

Abstract

Orexin receptor antagonists are a group of medications primarily developed to treat insomnia. Preliminary studies support their efficacy in the treatment of depression. In this systematic review, we aim to evaluate the efficacy of orexin receptor antagonists for the treatment of major depressive disorder (MDD). Electronic databases were searched from inception to February 2024 to find relevant studies. Original studies in English that evaluated efficacy of orexin receptor antagonists were included. A total of five randomized clinical trials involving 498 participants were included. Seltorexant (20 mg) significantly decreased depression scores when compared to placebo, as measured by the Hamilton Depression Rating Scale (HDRS). In patients with inadequate responses to antidepressants, seltorexant (20 mg) also showed improvement in Montgomery-Ǻsberg Depression Rating Scale (MADRS) total scores compared to placebo. However, filorexant did not exhibit a significant difference in MADRS total scores compared to placebo. A separate study on seltorexant (40 mg) for MDD patients resulted in a non-significant decrease in depressive symptoms compared to placebo, as measured by the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Taken together, these findings highlight the potential of orexin receptor antagonists, particularly seltorexant, as a novel avenue for managing depressive symptoms in MDD. Further research is warranted to better understand their role in depression treatment and their safety profile.

Keywords: Depression; Major depressive disorder; Orexin; Orexin receptor antagonist; Seltorexant.

Publication types

Review