The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis

Tao Xue; Xin Wu; Shujun Chen; Yanbo Yang; Zeya Yan; Zhaoming Song; Wei Zhang; Jianguo Zhang; Zhouqing Chen; Zhong Wang

doi:10.1016/j.smrv.2021.101573

The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis

Sleep Med Rev. 2022 Feb:61:101573. doi: 10.1016/j.smrv.2021.101573. Epub 2021 Nov 26.

Authors

Tao Xue¹, Xin Wu², Shujun Chen³, Yanbo Yang⁴, Zeya Yan⁴, Zhaoming Song⁴, Wei Zhang⁵, Jianguo Zhang⁶, Zhouqing Chen⁷, Zhong Wang⁸

Affiliations

¹ Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China; Department of Neurosurgery, Suzhou Ninth People's Hospital, Suzhou, 215200, China.
³ Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
⁴ Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
⁵ Department of Neurosurgery, Suzhou Ninth People's Hospital, Suzhou, 215200, China.
⁶ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing, China; Beijing Key Laboratory of Neurostimulation, Beijing, China. Electronic address: zjguo73@126.com.
⁷ Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. Electronic address: zqchen6@163.com.
⁸ Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. Electronic address: wangzhong761@163.com.

PMID: 34902823
DOI: 10.1016/j.smrv.2021.101573

Abstract

The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs) over the past several decades. However, there have been few systematic comparisons of different DORAs, and the best DORA for insomniacs has remained unclear. Here, Medline, Embase, Cochrane library, and clinicaltrials.gov were searched for RCTs (through December 31, 2020) to evaluate different DORAs versus a placebo. We pooled data from 13 RCTs. DORAs were superior to the placebo in all efficacy outcomes except the subjective number of awakenings (P = 0.90), but also showed higher risks of somnolence, abnormal dreams, fatigue, and dry mouth (somnolence: P < 0.00001; abnormal dreams: P = 0.03; fatigue: P = 0.001; dry mouth: P = 0.007). No statistical differences were found between any two of the DORAs in terms of primary efficacy outcomes. However, lemborexant yielded the three-highest surfaces under the curve ranking area (SUCRA) values (78.25%, 96.25% and 89.13%). Taken together, we conclude that DORAs are superior to the placebo in terms of efficacy and safety measures.

Keywords: Dual orexin receptor antagonists; Lemborexant; Primary insomnia; Suvorexant; Systematic review.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Humans
Network Meta-Analysis
Orexin Receptor Antagonists* / adverse effects
Sleep Initiation and Maintenance Disorders* / drug therapy
Wakefulness

Substances

Orexin Receptor Antagonists