The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials

作者全名："Pan, Bei; Ge, Long; Lai, Honghao; Hou, Liangying; Tian, Chen; Wang, Qi; Yang, Kelu; Lu, Yao; Zhu, Hongfei; Li, Mengting; Wang, Deren; Li, Xiuxia; Zhang, Yuqing; Gao, Ya; Liu, Ming; Ding, Guowu; Tian, Jinhui; Yang, Kehu"

作者地址："[Pan, Bei; Hou, Liangying; Liu, Ming; Tian, Jinhui; Yang, Kehu] Lanzhou Univ, Evidence Based Med Ctr, Sch Basic Med Sci, 199 Donggang West Rd, Lanzhou 730000, Peoples R China; [Pan, Bei; Ge, Long; Lai, Honghao; Hou, Liangying; Tian, Chen; Lu, Yao; Zhu, Hongfei; Li, Mengting; Li, Xiuxia; Ding, Guowu; Yang, Kehu] Lanzhou Univ, Evidence Based Social Sci Res Ctr, Sch Publ Hlth, 199 Donggang West Rd, Lanzhou 730000, Peoples R China; [Pan, Bei; Ge, Long; Hou, Liangying; Li, Xiuxia; Tian, Jinhui; Yang, Kehu] Key Lab Evidence Based Med & Knowledge Translat Ga, Lanzhou, Peoples R China; [Wang, Qi] Shandong Univ, Sch Publ Hlth, Dept Epidemiol, Jinan, Peoples R China; [Yang, Kelu] KU Leuven Univ Leuven, Acad Ctr Nursing & Midwifery, Dept Publ Hlth & Primary Care, Leuven, Belgium; [Wang, Deren] Sichuan Univ, West China Hosp, Dept Neurol, Chengdu, Peoples R China; [Zhang, Yuqing] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing, Peoples R China; [Gao, Ya] McMaster Univ, Dept Hlth Res Methods Evidence & Impact, Hamilton, ON, Canada"

通信作者："Yang, KH (通讯作者)，Lanzhou Univ, Evidence Based Med Ctr, Sch Basic Med Sci, 199 Donggang West Rd, Lanzhou 730000, Peoples R China.; Ge, L; Yang, KH (通讯作者)，Lanzhou Univ, Evidence Based Social Sci Res Ctr, Sch Publ Hlth, 199 Donggang West Rd, Lanzhou 730000, Peoples R China.; Ge, L; Yang, KH (通讯作者)，Key Lab Evidence Based Med & Knowledge Translat Ga, Lanzhou, Peoples R China."

来源：DRUGS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000983501700001

JCR分区：Q1

影响因子：13

年份：2023

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期号：　

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结束页：　

文献类型：Review; Early Access

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摘要："BackgroundPharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia.MethodsIn this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings.ResultsA total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty).ConclusionsNon-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability.Protocol registration PROSPERO (CRD42019138790)."

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