Lu Changhong, Geng Yuanyuan, Guan Xiaoli, Meng Ying, Zhu Mucheng, Zhao Yuan
Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou, China.
Ophthalmology Department of the Second Hospital of Lanzhou University, Lanzhou, China.
Front Psychiatry. 2025 Jul 9;16:1461166. doi: 10.3389/fpsyt.2025.1461166. eCollection 2025.
The clinical decision-making to insomnia drugs should comprehensively weight its risks.
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.
We conducted Bayesian network meta-analyses and fixed-effects Mantel-Haenszel network meta-analyses to estimate the relative safety between treatments.
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 hematuria.
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.
https://www.crd.york.ac.uk/prospero/, identifier CRD42022344981.
失眠药物的临床决策应全面权衡其风险。
对随机对照试验进行系统评价和网状Meta分析，比较不同失眠药物治疗成人失眠的不良反应。
我们进行了贝叶斯网状Meta分析和固定效应Mantel-Haenszel网状Meta分析，以评估各治疗方法之间的相对安全性。
与安慰剂相比，唑吡坦（嗜睡：相对危险度[RR]1.85；头晕：RR 2.33；头痛：RR 1.26）、佐匹克隆（嗜睡：RR 2.02；头晕：RR 2.33；味觉障碍：RR 7.84）、因地普隆（嗜睡：RR 3.46；头晕：RR 2.30；头痛：RR 1.63）、加波沙朵（头晕：RR 3.44）、艾司佐匹克隆（嗜睡：RR 2.00；头晕：RR 3.18；味觉障碍：RR 10.54）、艾司唑仑（嗜睡：RR 2.08）、氟硝西泮（嗜睡：RR 3.04）、氟西泮（嗜睡：RR 2.52）、伦扎必利（嗜睡：RR 6.57）、硝西泮（嗜睡：RR 3.80）、雷美替胺（嗜睡：RR 2.19）、苏沃雷生（嗜睡：RR 3.32）、替马西泮（嗜睡：RR 3.77）、曲唑酮（嗜睡：RR 2.86）、三唑仑（嗜睡：RR 2.35）和米氮平（嗜睡：RR 4.63；头晕：RR 2.87）在神经系统疾病方面不良反应最为严重。此外，与安慰剂相比，还发现唑吡坦与口干（RR 1.92）和焦虑（RR 3.32）有关；加波沙朵与恶心/呕吐（RR 3.49）有关；艾司佐匹克隆与口干（RR 4.39）有关。多塞平与头痛和嗜睡的风险低于安慰剂或/和大多数其他药物，且不良反应发生率也较低。我们未观察到药物与包括鼻咽炎、呼吸问题、意外伤害、感染、上呼吸道感染、鼻窦炎或血尿在内的严重不良反应风险之间存在关联。
大多数药物与神经系统疾病和胃肠道疾病呈正相关。氟西泮、硝西泮、三唑仑和扎来普隆等一些药物在某些结局方面的数据主要基于有限的研究且事件罕见，因此高度不确定，无法得出确切结论。
