PMID- 36947394
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230522
IS  - 1179-1950 (Electronic)
IS  - 0012-6667 (Linking)
VI  - 83
IP  - 7
DP  - 2023 May
TI  - The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review 
      and Network Meta-Analysis of 153 Randomized Trials.
PG  - 587-619
LID - 10.1007/s40265-023-01859-8 [doi]
AB  - BACKGROUND: Pharmacological 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. 
      METHODS: In 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. RESULTS: 
      A 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). CONCLUSIONS: Non-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).
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Pan, Bei
AU  - Pan B
AD  - Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
AD  - Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu 
      Province, Lanzhou, China.
FAU - Ge, Long
AU  - Ge L
AUID- ORCID: 0000-0002-3555-1107
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China. gelong2009@163.com.
AD  - Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu 
      Province, Lanzhou, China. gelong2009@163.com.
FAU - Lai, Honghao
AU  - Lai H
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Hou, Liangying
AU  - Hou L
AD  - Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
AD  - Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu 
      Province, Lanzhou, China.
FAU - Tian, Chen
AU  - Tian C
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Wang, Qi
AU  - Wang Q
AD  - Department of Epidemiology, School of Public Health, Shandong University, Jinan, 
      China.
FAU - Yang, Kelu
AU  - Yang K
AD  - Department of Public Health and Primary Care, Academic Centre for Nursing and 
      Midwifery, KU Leuven-University of Leuven, Leuven, Belgium.
FAU - Lu, Yao
AU  - Lu Y
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Zhu, Hongfei
AU  - Zhu H
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Li, Mengting
AU  - Li M
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Wang, Deren
AU  - Wang D
AD  - Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
FAU - Li, Xiuxia
AU  - Li X
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
AD  - Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu 
      Province, Lanzhou, China.
FAU - Zhang, Yuqing
AU  - Zhang Y
AD  - Department of Neurology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
FAU - Gao, Ya
AU  - Gao Y
AD  - Department of Health Research Methods, Evidence and Impact, McMaster University, 
      Hamilton, ON, Canada.
FAU - Liu, Ming
AU  - Liu M
AD  - Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Ding, Guowu
AU  - Ding G
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
FAU - Tian, Jinhui
AU  - Tian J
AD  - Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China.
AD  - Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu 
      Province, Lanzhou, China.
FAU - Yang, Kehu
AU  - Yang K
AD  - Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China. yangkh-ebm@lzu.edu.cn.
AD  - Evidence-Based Social Science Research Center, School of Public Health, Lanzhou 
      University, No. 199 Donggang West Road, Chengguan District, Lanzhou, 730000, 
      China. yangkh-ebm@lzu.edu.cn.
AD  - Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu 
      Province, Lanzhou, China. yangkh-ebm@lzu.edu.cn.
LA  - eng
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20230322
PL  - New Zealand
TA  - Drugs
JT  - Drugs
JID - 7600076
RN  - 0 (Antidepressive Agents)
SB  - IM
MH  - Humans
MH  - *Sleep Initiation and Maintenance Disorders/drug therapy
MH  - Network Meta-Analysis
MH  - Randomized Controlled Trials as Topic
MH  - Antidepressive Agents/therapeutic use
MH  - Sleep
EDAT- 2023/03/23 06:00
MHDA- 2023/05/22 06:42
CRDT- 2023/03/22 12:24
PHST- 2023/03/05 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/03/23 06:00 [pubmed]
PHST- 2023/03/22 12:24 [entrez]
AID - 10.1007/s40265-023-01859-8 [pii]
AID - 10.1007/s40265-023-01859-8 [doi]
PST - ppublish
SO  - Drugs. 2023 May;83(7):587-619. doi: 10.1007/s40265-023-01859-8. Epub 2023 Mar 22.