5- α还原酶抑制剂与自杀和抑郁风险之间的信号检测：一项国际药物警戒分析

IF 2.7 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-08-01 Epub Date: 2025-06-06 DOI:10.1007/s00228-025-03851-5

Soyun Lee, Hyesu Jo, Guillaume Fond, Laurent Boyer, Lee Smith, André Hajek, Dong Keon Yon

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引用次数: 0

摘要

目的：本研究旨在探讨非那雄胺和度他雄胺的使用与自杀行为的发生，包括自杀意念、自杀企图和自杀未遂，以及抑郁症的发生之间的信号检测。方法：本研究利用了来自全球药物警戒数据库的数据，该数据库包含来自140多个国家的3500多万份不良事件报告。自杀和抑郁由MedDRA术语26.0版定义。为了分析数据，采用了两个完善的药物警戒指标：信息成分（IC）和报告优势比（ROR）。结果：在非那雄胺和度他雄胺的信号检测中，分别发现了395例和1299例自杀和抑郁报告。报告趋势表明，病例首次出现于1992年，2010年之后显著增加。主要分析确定了非那雄胺使用与自杀之间的信号检测(ROR, 7.28 [95% CI, 6.57-8.06]；IC, 2.82 [IC0.25, 2.65])和抑郁(ROR, 28.18 [95% CI, 26.57-29.89]；IC, 4.68 [IC0.25, 4.58])，而度他雄胺对自杀没有显著的信号，对抑郁症的信号较弱(ROR, 3.23 [95% CI, 2.61-4.00]；Ic, 1.66 [ic0.25, 1.30])。在亚组分析中，年轻个体（18-44岁）与非那雄胺相关的自杀倾向（IC, 3.54 [IC0.25, 3.27]）和抑郁倾向（IC, 5.25 [IC0.25, 5.05]）的信号特别强，表明该年龄组的易感性较高。出现自杀和抑郁的时间以服药3个月后为主，平均发生自杀的时间为114.92天，出现抑郁的时间为93.31天。结论：虽然我们的研究并不意味着因果关系，但这一发现表明，非那雄胺使用与自杀和抑郁相关的报告在统计上存在显著的不相称性，并增加了自杀和抑郁的信号风险，强调需要进一步的大规模流行病学研究来证实这些发现并调查其潜在机制。

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Signal detection between 5-alpha reductase inhibitors and the risk of suicidality and depression: an international pharmacovigilance analysis.

Objective: This study aims to investigate the signal detection between the use of finasteride and dutasteride and the occurrence of suicidality, including suicidal ideation, attempts, and completed suicide, as well as the development of depression.

Methods: This study utilized data from a global pharmacovigilance database encompassing over 35 million adverse event reports from more than 140 countries. Suicidality and depression were defined by MedDRA terms version 26.0. To analyze the data, two well-established pharmacovigilance indicators were applied: the information component (IC) and the reporting odds ratio (ROR).

Results: A total of 395 and 1299 reports of suicidality and depression, respectively, were identified in signal detection with finasteride and dutasteride. Reporting trends showed that cases first emerged in 1992, with a notable increase after 2010. The main analysis identified signal detections between finasteride use and both suicidality (ROR, 7.28 [95% CI, 6.57-8.06]; IC, 2.82 [IC_0.25, 2.65]) and depression (ROR, 28.18 [95% CI, 26.57-29.89]; IC, 4.68 [IC_0.25, 4.58]), whereas dutasteride showed no significant signal for suicidality and a weaker signal with depression (ROR, 3.23 [95% CI, 2.61-4.00]; IC, 1.66 [IC_0.25, 1.30]). In subgroup analysis, younger individuals (18-44 years) had particularly strong signals for suicidality (IC, 3.54 [IC_0.25, 3.27]), and depression (IC, 5.25 [IC_0.25, 5.05]) associated with finasteride, suggesting a heightened susceptibility in this age group. The time to onset of suicidality and depression was predominantly reported after 3 months of drug administration, with suicidality occurring at an average of 114.92 days and depression at 93.31 days.

Conclusions: Although our study does not imply causality, this findings suggest a statistically significant disproportionality in reports of suicidality and depression associated with finasteride use and increased signal risks of suicidality and depression highlighting the need for further large-scale epidemiological studies to confirm these findings and investigate the underlying mechanisms.

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.