Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant

Habibolah Khazaie; Masoud Sadeghi; Sepideh Khazaie; Max Hirshkowitz; Amir Sharafkhaneh

doi:10.3389/fpsyt.2022.1070522

Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant

Front Psychiatry. 2022 Dec 12:13:1070522. doi: 10.3389/fpsyt.2022.1070522. eCollection 2022.

Authors

Habibolah Khazaie¹, Masoud Sadeghi^{2

3}, Sepideh Khazaie¹, Max Hirshkowitz^{4

5}, Amir Sharafkhaneh⁵

Affiliations

¹ Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
² Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
³ Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
⁴ Public Health Division, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA, United States.
⁵ Sleep Disorders and Research Center, Baylor College of Medicine, Houston, TX, United States.

Abstract

Study objectives: Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.

Methods: We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome.

Results: Our search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo.

Conclusion: The present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.

Keywords: insomnia; lemborexant; meta-analysis; orexin receptor antagonist; randomized trial; suvorexant.

Publication types

Systematic Review