Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis

BackgroundThe clinical decision-making to insomnia drugs should comprehensively weight its risks.ObjectiveTo perform a systematic review and network meta-analysis of randomized controlled trials to compare the AEs associated with different insomnia drugs for adults with insomnia.MethodsWe conducted...

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Main Authors: Changhong Lu, Yuanyuan Geng, Xiaoli Guan, Ying Meng, Mucheng Zhu, Yuan Zhao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1461166/full
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author Changhong Lu
Yuanyuan Geng
Xiaoli Guan
Ying Meng
Mucheng Zhu
Yuan Zhao
author_facet Changhong Lu
Yuanyuan Geng
Xiaoli Guan
Ying Meng
Mucheng Zhu
Yuan Zhao
author_sort Changhong Lu
collection DOAJ
description BackgroundThe clinical decision-making to insomnia drugs should comprehensively weight its risks.ObjectiveTo perform a systematic review and network meta-analysis of randomized controlled trials to compare the AEs associated with different insomnia drugs for adults with insomnia.MethodsWe conducted Bayesian network meta-analyses and fixed-effects Mantel-Haenszel network meta-analyses to estimate the relative safety between treatments.ResultsCompared with placebo, zolpidem (somnolence: relative risk [RR] 1.85; dizziness: RR 2.33; headache: RR 1.26), zopiclone (somnolence: RR 2.02; dizziness: RR 2.33; dysgeusia: RR 7.84), indiplon (somnolence: RR 3.46; dizziness: RR 2.30; headache: RR 1.63), gaboxadol (dizziness: RR 3.44), eszopiclone (somnolence: RR 2.00; dizziness: RR 3.18; dysgeusia: RR 10.54), estazolam (somnolence: RR 2.08), flunitrazepam (somnolence: RR 3.04), flurazepam (somnolence: RR 2.52), lemborexant (somnolence: RR 6.57), nitrazepam (somnolence: RR 3.80), Ramelteon (somnolence: RR 2.19), suvorexant (somnolence: RR 3.32), Temazepam (somnolence: RR 3.77), trazodone (somnolence: RR 2.86), triazolam (somnolence: RR 2.35), and esmirtazapine (somnolence: RR 4.63; dizziness: RR 2.87) had the most harmful profile in nervous system disorders. Additionally, compared to placebo, zolpidem was also found to be associated with dry mouth (RR 1.92) and anxiety (RR 3.32); gaboxadol was associated with nausea/vomiting (RR 3.49); and eszopiclone was associated with dry mouth (RR 4.39). Doxepin was associated with lower risk of headache and somnolence than placebo or/and most of other drugs, and had also a lower rate of AEs. We observed no associations between drugs and the risks of serious AEs including nasopharyngitis, respiratory problem, accidental injury, infection, upper respiratory tract infection, sinusitis, or hematuria.ConclusionsMost drugs were positive associated with nervous system disorders and gastrointestinal disorders. Data on some drugs like flurazepam, nitrazepam, triazolam, and zaleplon in some outcomes were mainly based on limited study with rare event and thus was highly uncertain and do not allow firm conclusions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022344981.
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spelling doaj-art-97da97c754d14ff6b78a914f3e7339bf2025-08-20T03:50:06ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-07-011610.3389/fpsyt.2025.14611661461166Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysisChanghong Lu0Yuanyuan Geng1Xiaoli Guan2Ying Meng3Mucheng Zhu4Yuan Zhao5Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou, ChinaOphthalmology Department of the Second Hospital of Lanzhou University, Lanzhou, ChinaDepartment of General Medicine, The Second Hospital of Lanzhou University, Lanzhou, ChinaDepartment of General Medicine, The Second Hospital of Lanzhou University, Lanzhou, ChinaDepartment of General Medicine, The Second Clinical College of Lanzhou University, Lanzhou, ChinaDepartment of General Medicine, The Second Hospital of Lanzhou University, Lanzhou, ChinaBackgroundThe clinical decision-making to insomnia drugs should comprehensively weight its risks.ObjectiveTo perform a systematic review and network meta-analysis of randomized controlled trials to compare the AEs associated with different insomnia drugs for adults with insomnia.MethodsWe conducted Bayesian network meta-analyses and fixed-effects Mantel-Haenszel network meta-analyses to estimate the relative safety between treatments.ResultsCompared with placebo, zolpidem (somnolence: relative risk [RR] 1.85; dizziness: RR 2.33; headache: RR 1.26), zopiclone (somnolence: RR 2.02; dizziness: RR 2.33; dysgeusia: RR 7.84), indiplon (somnolence: RR 3.46; dizziness: RR 2.30; headache: RR 1.63), gaboxadol (dizziness: RR 3.44), eszopiclone (somnolence: RR 2.00; dizziness: RR 3.18; dysgeusia: RR 10.54), estazolam (somnolence: RR 2.08), flunitrazepam (somnolence: RR 3.04), flurazepam (somnolence: RR 2.52), lemborexant (somnolence: RR 6.57), nitrazepam (somnolence: RR 3.80), Ramelteon (somnolence: RR 2.19), suvorexant (somnolence: RR 3.32), Temazepam (somnolence: RR 3.77), trazodone (somnolence: RR 2.86), triazolam (somnolence: RR 2.35), and esmirtazapine (somnolence: RR 4.63; dizziness: RR 2.87) had the most harmful profile in nervous system disorders. Additionally, compared to placebo, zolpidem was also found to be associated with dry mouth (RR 1.92) and anxiety (RR 3.32); gaboxadol was associated with nausea/vomiting (RR 3.49); and eszopiclone was associated with dry mouth (RR 4.39). Doxepin was associated with lower risk of headache and somnolence than placebo or/and most of other drugs, and had also a lower rate of AEs. We observed no associations between drugs and the risks of serious AEs including nasopharyngitis, respiratory problem, accidental injury, infection, upper respiratory tract infection, sinusitis, or hematuria.ConclusionsMost drugs were positive associated with nervous system disorders and gastrointestinal disorders. Data on some drugs like flurazepam, nitrazepam, triazolam, and zaleplon in some outcomes were mainly based on limited study with rare event and thus was highly uncertain and do not allow firm conclusions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022344981.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1461166/fulladverse eventssafetyinsomnia drugnetwork meta-analysissystematic review
spellingShingle Changhong Lu
Yuanyuan Geng
Xiaoli Guan
Ying Meng
Mucheng Zhu
Yuan Zhao
Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
Frontiers in Psychiatry
adverse events
safety
insomnia drug
network meta-analysis
systematic review
title Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
title_full Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
title_fullStr Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
title_full_unstemmed Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
title_short Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
title_sort adverse events of pharmacological interventions for insomnia disorder in adults a systematic review and network meta analysis
topic adverse events
safety
insomnia drug
network meta-analysis
systematic review
url https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1461166/full
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