Orexin Receptor Antagonists for Sleep Disorders: Comparing Lemborexant with Suvorexant

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New data demonstrate suvorexant and lemborexant were equally effective in improving sleep status, but lemborexant may cause side effects less frequently.

New research found no difference in the effectiveness of suvorexant and lemborexant in improving sleep status. However, lemborexant may cause side effects less frequently than suvorexant, at least in the early stages of treatment based on the study results.1

This suggests that both drugs may be viable treatment options for sleep disorders like insomnia, but lemborexant could be a better option for patients who are prone to side effects.

Sleep disorders are common worldwide and can have a significant impact on an individual’s quality of life. The use of medications to promote sleep has increased over the years, with orexin receptor antagonists being one of the newer classes of drugs used for this purpose.

Suvorexant and lemborexant are approved therapies for use as sleep medications in Japan. While both drugs have similar mechanisms of action, no studies have directly compared their efficacy and safety.

Teruaki Hayashi MD, PhD, Department of Neuropsychiatry, Faculty of Medicine, Tottori University, and a team of investigators aimed to compare the efficacy and safety of suvorexant and lemborexant in patients with sleep disorders.

The team found no significant difference between the Clinical Global Impressions-Improvement (CGI-I) Scale scores in the suvorexant (mean [SD], 3.05 [0.93]) and lemborexant groups (mean [SD], 3.38 [0.83]) (p = 0.10), indicating similar efficacy in improving sleep status.

However, the incidence of side effects with continued treatment was observed to be lower in the lemborexant group (2.9%) compared with the suvorexant group (12.5%), although this difference was not statistically significant (p = 0.10). Patients who switched from suvorexant to lemborexant had CGI-I scores ≤4, and no side effects were observed after switching to lemborexant.

The study included 108 patients who were newly treated with either suvorexant or lemborexant between December 2020–December 2021. Data were collected retrospectively from medical records and analyzed after excluding one case of discontinuation due to a post-administration allergic reaction.

The CGI-I Scale, a subscale of the Clinical Global Impressions (CGI) Scale, was used to assess the improvement in sleep status after drug administration. The incidence of side effects was obtained from the medical records of the patient's first visit after administration.

While this retrospective cohort study provided important insights into the efficacy and safety of suvorexant and lemborexant for sleep disorders, it has several limitations that should be considered. Firstly, only one evaluator scored the CGI Scale, which can be influenced by evaluator subjectivity and may not be reproducible due to its single-item structure.

Secondly, the study used CGI-Improvement (CGI-I) scores instead of a sleep-specific index to evaluate the efficacy of each drug. The CGI score has traditionally been used to assess the overall function of patients with psychiatric disorders, and while recent reports indicated that it could be a substitute for conventional rating scales in some cases, it might not capture all aspects of sleep disorder treatment.

Investigators noted that future studies could consider using a more comprehensive sleep-specific index to evaluate the efficacy of these drugs and involve multiple evaluators to reduce the potential impact of evaluator subjectivity. By addressing these limitations, future studies can build on the findings of this study and provide more robust evidence on the comparative efficacy and safety of suvorexant and lemborexant for sleep disorders.


  1. Hayashi, T, Yamanashi, T, Iwata, M. Comparative efficacy and safety of suvorexant and lemborexant for insomnia treatment. Psychiatry Clin Neurosci Rep. 2023; 2:e85.