Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis.

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-08-01 Epub Date: 2025-03-25 DOI:10.1007/s00213-025-06773-3

Ming Tang, Ziyi Shen, Peilu Yu, Meiling Yu, Xiaoqiong Tong, Guohui Jiang

{"title":"Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis.","authors":"Ming Tang, Ziyi Shen, Peilu Yu, Meiling Yu, Xiaoqiong Tong, Guohui Jiang","doi":"10.1007/s00213-025-06773-3","DOIUrl":null,"url":null,"abstract":"Objective: To systematically evaluate the clinical efficacy of lemborexant (LEM) and daridorexant (DAR) for the treatment of insomnia, including the difference in efficacy and safety.Methods: In this systematic review and meta-analysis, we searched the randomized controlled trials (RCTs) comparing the efficacy and safety of LEM and DAR in patients with insomnia in five databases from database inception to Mar 16, 2024. We evaluate the quality of studies. Besides, we perform the meta-analysis and detect publication bias.Results: A total of 8 RCTs with 5077 patients were included in this study, including 2239 in the LEM treatment group, 1397 in the DAR treatment group, and 1441 in the placebo (PBO) control group. Both LEM and DAR significantly improved sleep outcomes compared to placebo. LEM was more effective in reducing the time of wake after sleep onset (WASO) (MD, -45.15; 95% CI: -51.75 to -38.56; P < 0.001) and improving subjective sleep onset latency (sSOL) (MD, -25.01; 95% CI: -28.58 to -21.44; P < 0.001) than DAR (WASO: MD: -12.6; 95% CI: -18.71 to -6.5; P < 0.001; sSOL: MD, -2.33; 95% CI: -7.1 to 2.45; P = 0.24). In terms of dosing, DAR at 50 mg demonstrated superior efficacy compared to the 5 mg, 10 mg, and 25 mg doses, indicating a dose-dependent effect. The efficacy of LEM was consistent across the 5 mg and 10 mg doses. Safety profiles revealed that DAR (RR, 1.16; 95% CI: 1.03 to 1.29; P = 0.01) treatment was associated with higher rates of treatment-emergent adverse events (TEAEs) compared to placebo, particularly at the 25 mg dose (RR, 1.15; 95% CI: 1.02 to 1.31; P = 0.03), while LEM (RR, 1.21; 95% CI: 0.98 to 1.50; P = 0.08) showed no significant difference in TEAEs rates compared to placebo. However, LEM (RR, 5.62; 95% CI: 2.92 to 10.83; P < 0.001) was associated with a higher risk of somnolence compared to DAR (RR, 1.55; 95% CI: 0.86 to 2.81; P = 0.15). The overall quality of the included studies was moderate to high based on the risk of bias assessment.Conclusion: Both LEM and DAR are effective and generally safe options for the treatment of insomnia, with LEM showing greater efficacy in improving WASO and sSOL. The choice between LEM and DAR should consider individual patient needs, including the risk of daytime drowsiness and other adverse events. Further direct comparative trials are needed to confirm these findings and inform clinical decision-making.","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1693-1711"},"PeriodicalIF":3.3000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06773-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/25 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: To systematically evaluate the clinical efficacy of lemborexant (LEM) and daridorexant (DAR) for the treatment of insomnia, including the difference in efficacy and safety.

Methods: In this systematic review and meta-analysis, we searched the randomized controlled trials (RCTs) comparing the efficacy and safety of LEM and DAR in patients with insomnia in five databases from database inception to Mar 16, 2024. We evaluate the quality of studies. Besides, we perform the meta-analysis and detect publication bias.

Results: A total of 8 RCTs with 5077 patients were included in this study, including 2239 in the LEM treatment group, 1397 in the DAR treatment group, and 1441 in the placebo (PBO) control group. Both LEM and DAR significantly improved sleep outcomes compared to placebo. LEM was more effective in reducing the time of wake after sleep onset (WASO) (MD, -45.15; 95% CI: -51.75 to -38.56; P < 0.001) and improving subjective sleep onset latency (sSOL) (MD, -25.01; 95% CI: -28.58 to -21.44; P < 0.001) than DAR (WASO: MD: -12.6; 95% CI: -18.71 to -6.5; P < 0.001; sSOL: MD, -2.33; 95% CI: -7.1 to 2.45; P = 0.24). In terms of dosing, DAR at 50 mg demonstrated superior efficacy compared to the 5 mg, 10 mg, and 25 mg doses, indicating a dose-dependent effect. The efficacy of LEM was consistent across the 5 mg and 10 mg doses. Safety profiles revealed that DAR (RR, 1.16; 95% CI: 1.03 to 1.29; P = 0.01) treatment was associated with higher rates of treatment-emergent adverse events (TEAEs) compared to placebo, particularly at the 25 mg dose (RR, 1.15; 95% CI: 1.02 to 1.31; P = 0.03), while LEM (RR, 1.21; 95% CI: 0.98 to 1.50; P = 0.08) showed no significant difference in TEAEs rates compared to placebo. However, LEM (RR, 5.62; 95% CI: 2.92 to 10.83; P < 0.001) was associated with a higher risk of somnolence compared to DAR (RR, 1.55; 95% CI: 0.86 to 2.81; P = 0.15). The overall quality of the included studies was moderate to high based on the risk of bias assessment.

Conclusion: Both LEM and DAR are effective and generally safe options for the treatment of insomnia, with LEM showing greater efficacy in improving WASO and sSOL. The choice between LEM and DAR should consider individual patient needs, including the risk of daytime drowsiness and other adverse events. Further direct comparative trials are needed to confirm these findings and inform clinical decision-making.

查看原文本刊更多论文

双食欲素受体拮抗剂lemborexant和daridorexant治疗失眠的疗效和安全性比较：一项系统回顾和荟萃分析。

目的：系统评价lemborexant （LEM）与daridorexant （DAR）治疗失眠症的临床疗效，包括疗效和安全性的差异。方法：在本系统综述和荟萃分析中，我们检索了从数据库建立到2024年3月16日五个数据库中比较LEM和DAR治疗失眠患者疗效和安全性的随机对照试验（RCTs）。我们评估研究的质量。此外，我们进行了荟萃分析并检测了发表偏倚。结果：本研究共纳入8项rct，共5077例患者，其中LEM治疗组2239例，DAR治疗组1397例，安慰剂（PBO）对照组1441例。与安慰剂相比，LEM和DAR均显著改善了睡眠结果。LEM在减少睡眠后醒来时间（WASO）方面更有效(MD, -45.15；95% CI: -51.75 ~ -38.56；结论：LEM和DAR都是治疗失眠的有效且安全的选择，LEM在改善WASO和sSOL方面表现出更大的疗效。在LEM和DAR之间的选择应考虑患者的个体需求，包括白天嗜睡和其他不良事件的风险。需要进一步的直接比较试验来证实这些发现并为临床决策提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.