SYSTEMATIC REVIEW article
Front. Psychiatry
Sec. Psychopharmacology
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1461166
Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis
Provisionally accepted
- Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
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Background: The clinical decision-making to insomnia drugs should comprehensively weight its risks. Objective: To 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.Methods: We conducted Bayesian network meta-analyses and fixed-effects Mantel-Haenszel network meta-analyses to estimate the relative safety between treatments.Results: Compared 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 haematuria. Conclusions: Most 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.
Keywords: adverse events, safety, insomnia drug, network meta-analysis Compared with placebo, zolpidem (somnolence: relative risk [RR] 1.85, dizziness: RR 2.33, headache: RR 1.26), zopiclone (somnolence: RR 2.02, 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, dizziness: RR adverse events, safety, insomnia drug, network meta-analysis
Received: 22 Jul 2024; Accepted: 31 May 2025.
Copyright: © 2025 Zhao, Lu, Geng, Guan, Meng and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuan Zhao, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu Province, China
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