Meshkat Shakila, Kwan Angela T H, Le Gia Han, Wong Sabrina, Teopiz Kayla M, Wang Larry, Rosenblat Joshua D, Rhee Taeho Greg, Cao Bing, McIntyre Roger S
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
J Affect Disord. 2025 Mar 1;372:409-419. doi: 10.1016/j.jad.2024.12.008. Epub 2024 Dec 4.
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.
食欲素受体拮抗剂是一类主要用于治疗失眠的药物。初步研究支持其在治疗抑郁症方面的疗效。在本系统评价中，我们旨在评估食欲素受体拮抗剂治疗重度抑郁症（MDD）的疗效。检索了从数据库建立至2024年2月的电子数据库以查找相关研究。纳入了评估食欲素受体拮抗剂疗效的英文原创研究。共纳入了五项涉及498名参与者的随机临床试验。根据汉密尔顿抑郁量表（HDRS）测量，与安慰剂相比，塞托雷生（20毫克）显著降低了抑郁评分。在对抗抑郁药反应不足的患者中，与安慰剂相比，塞托雷生（20毫克）在蒙哥马利-Åsberg抑郁量表（MADRS）总分上也有改善。然而，与安慰剂相比，非雷生在MADRS总分上没有显著差异。一项针对MDD患者使用塞托雷生（40毫克）的单独研究显示，根据抑郁症状快速自评量表（QIDS-SR）测量，与安慰剂相比，抑郁症状有非显著下降。综上所述，这些发现凸显了食欲素受体拮抗剂，尤其是塞托雷生，作为治疗MDD抑郁症状的新途径的潜力。有必要进行进一步研究以更好地了解它们在抑郁症治疗中的作用及其安全性。
