1967 - 2024年失眠症药物相关自杀倾向的全球负担：全球药物警戒数据库的不均衡分析
Global burden of insomnia medication-associated suicidality, 1967-2024: A disproportionality analysis of the global pharmacovigilance database.
作者信息
Kim Tae Hyeon, Lee Kyeongmin, Lee Suhyun, Hwang Jiyoung, Cho Hanseul, Fond Guillaume, Boyer Laurent, Chung Eun Kyoung, Yon Dong Keon
机构信息
Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea; Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea.
Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, South Korea.
出版信息
Psychiatry Res. 2025 Sep;351:116587. doi: 10.1016/j.psychres.2025.116587. Epub 2025 Jun 8.
BACKGROUND
While insomnia is recognized as a risk factor for suicidality, the potential influence of insomnia medications on this risk requires further investigation.
METHODS
We utilized the global pharmacovigilance database, to detect pharmacovigilance signal of insomnia medication-related suicidality from 1967 to 2024. The analysis included benzodiazepines, Z-drugs, antidepressants, first-generation H1 antagonists, and dual orexin receptor antagonists for insomnia medications. Multivariable logistic regression models were used to calculate the reporting odds ratio (ROR) and 95 % confidence interval (CI) of suicidality for each medication class, adjusting for age, sex, and reporting region, with melatonin and its receptor agonist as the reference.
RESULTS
We identified 13,899 reports of suicidality associated with insomnia medications. Benzodiazepines (ROR, 1.78 [95 % CI, 1.62-1.97]), Z-drugs (1.52 [1.40-1.66]), antidepressants (2.08 [1.88-2.31]), and first-generation H1 antagonists (1.59 [1.45-1.73]) showed stronger signal of suicidality compared to melatonin and its receptor agonist. In contrast, dual orexin receptor antagonists (ROR, 0.36 [0.31-0.42]) exhibited a lower signal risk. The melatonin receptor agonist ramelteon (ROR, 0.29 [0.21-0.39]) showed a weaker signal than melatonin. Similarly, dual orexin receptor antagonists suvorexant (ROR, 0.31 [0.26-0.37]), daridorexant (0.20 [0.14-0.29]), and lemborexant (0.24 [0.11-0.51]) significantly lowered the signal risk of suicidality compared to melatonin.
CONCLUSIONS
Although this disproportionality analysis did not permit causal interpretation, our study highlights significant variations in suicidality signal risk among insomnia medications, with benzodiazepines, Z-drugs, antidepressants, and first-generation H1 antagonists posing stronger signal, and dual orexin receptor antagonists presenting a weaker signal. Given the limitations of pharmacovigilance data, further studies are needed to confirm these findings and guide safer prescribing practices, particularly for individuals at high risk of suicidality.
背景
虽然失眠被认为是自杀倾向的一个风险因素，但失眠药物对这一风险的潜在影响仍需进一步研究。
方法
我们利用全球药物警戒数据库，检测1967年至2024年期间与失眠药物相关的自杀倾向的药物警戒信号。分析包括用于失眠治疗的苯二氮䓬类药物、Z类药物、抗抑郁药、第一代H1拮抗剂和双重食欲素受体拮抗剂。使用多变量逻辑回归模型计算每种药物类别自杀倾向的报告比值比（ROR）和95%置信区间（CI），并对年龄、性别和报告地区进行调整，以褪黑素及其受体激动剂作为对照。
结果
我们识别出13,899例与失眠药物相关的自杀倾向报告。与褪黑素及其受体激动剂相比，苯二氮䓬类药物（ROR，1.78 [95% CI，1.62 - 1.97]）、Z类药物（1.52 [1.40 - 1.66]）、抗抑郁药（2.08 [1.88 - 2.31]）和第一代H1拮抗剂（1.59 [1.45 - 1.73]）显示出更强的自杀倾向信号。相比之下，双重食欲素受体拮抗剂（ROR，0.36 [0.31 - 0.42]）的信号风险较低。褪黑素受体激动剂雷美替胺（ROR，0.29 [0.21 - 0.39]）的信号比褪黑素弱。同样，与褪黑素相比，双重食欲素受体拮抗剂苏沃雷生（ROR，0.31 [0.26 - 0.37]）、达利雷生（0.20 [0.14 - 0.29]）和伦扎雷生（0.24 [0.11 - 0.51]）显著降低了自杀倾向的信号风险。
结论
虽然这种不成比例分析不允许进行因果解释，但我们的研究突出了失眠药物之间自杀倾向信号风险的显著差异，苯二氮䓬类药物、Z类药物、抗抑郁药和第一代H1拮抗剂的信号较强，而双重食欲素受体拮抗剂的信号较弱。鉴于药物警戒数据的局限性，需要进一步研究来证实这些发现并指导更安全的处方实践，特别是对于有高自杀风险的个体。
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