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Review
. 2021 Dec;41(4):450-458.
doi: 10.1002/npr2.12205. Epub 2021 Sep 23.

Evidence-based insomnia treatment strategy using novel orexin antagonists: A review

Taro Kishi  1 , Maika Nishida  2 , Michinori Koebis  2 , Takehiro Taninaga  2 , Kenzo Muramoto  2 , Naoki Kubota  2 , Margaret Moline  3 , Kenji Sakuma  1 , Makoto Okuya  1 , Ikuo Nomura  1   4 , Nakao Iwata  1
Affiliations
Review

Evidence-based insomnia treatment strategy using novel orexin antagonists: A review

Taro Kishi et al. Neuropsychopharmacol Rep. 2021 Dec.

Abstract

Most conventional insomnia medications are gamma-aminobutylic acid receptor agonists. However, physical dependence is a concern and one of the major limiting factors for long-term treatment. The dual orexin receptor antagonists, suvorexant and lemborexant, were recently approved for treating chronic insomnia, giving a novel pharmacotherapeutic option. Because there are no comparative studies on these drugs, a network meta-analysis was conducted, which is suitable for comparing interventions. According to this analysis, 5- and 10-mg lemborexant were superior to 20-mg suvorexant because of the greater improvement in initiating sleep after 1-week administration. Furthermore, 5-mg lemborexant (not 10 mg) and suvorexant were similarly well tolerated, without requiring discontinuation due to adverse events. We also overviewed the pharmacological and pharmacokinetic properties of lemborexant and suvorexant that may support these clinical outcomes. When compared to suvorexant, lemborexant quickly binds to the orexin receptors. The time to reach the maximum concentration after multiple administrations is shorter for lemborexant than for suvorexant. Considering these results, we recommend 5-mg lemborexant as an initial treatment for insomnia, followed by 10-mg lemborexant or suvorexant.

Keywords: evidence-based medicine; insomnia; lemborexant; network meta-analysis; orexin.

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Conflict of interest statement

KT received speaker's honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, Mochida, MSD, and Tanabe‐Mitsubishi (Yoshitomi), a research grant from the Japanese Ministry of Health, Labour and Welfare (H29‐Seishin‐Ippan‐001, 19GC1012), a Grant‐in‐Aid for Scientific Research (C, 19K08082), Eisai, and a grant from the Fujita Health University School of Medicine (17‐012). MN, MK, TT, and KN are employees of Eisai Co., Ltd. KM was an employee of Eisai Co., Ltd. MM is an employee of Eisai Co., Inc KS received speaker's honoraria from Eisai, Kissei, Meiji, Otsuka, and Torii, a Fujita Health University School of Medicine research grant, and a Grant‐in‐Aid for Young Scientists (B). MO received a speaker's honoraria from Meiji. IN received speaker's honoraria from Meiji, MSD, Janssen, and Torii. Professor. NI received speaker's honoraria from Astellas, Dainipp on Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer as well as research grants from Eisai, Takeda, Dainippon Sumitomo, and Otsuka.

Figures

FIGURE 1
FIGURE 1
Time course of plasma suvorexant and lemborexant levels after repeated administration over 14 days. Data from Study 003 for SUV and Study 003 for LEM. Abbreviations: C max, maximum drug concentration; LEM, lemborexant; SUV, suvorexant
See this image and copyright information in PMC

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