Antidepressant use and Parkinson's disease risk: Overall protective effect with drug-specific variation.

IF 9.9 3区医学 Q1 PSYCHIATRY

General Psychiatry Pub Date : 2026-10-01 Epub Date: 2026-10-13 DOI:10.1002/gps3.70067

Ancha Baranova, Hongbao Cao, Chenxin Xu, Wenxi Sun, Dongming Liu, Fuquan Zhang

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引用次数: 0

Abstract

Background: Antidepressants can cause extrapyramidal side effects, but their impact on Parkinson's disease (PD) risk remains unclear.

Aims: We aimed to investigate the association between genetic liability to antidepressant use and PD.

Methods: We examined the causal effect of antidepressant use on PD using Mendelian randomisation (MR) analysis. We further performed multivariable MR (MVMR) analysis to determine the independent effect of genetic liability to antidepressant use on PD by accounting for the effect of major depressive disorder (MDD) on PD. The United States Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004 Q1-2024 Q2, 53.4 million event-level records) was mined to assess associations between 13 antidepressants and PD. Colocalisation analyses identified shared genetic variants between genetic liability to antidepressant use and PD.

Results: MR analyses demonstrated that genetic liability to antidepressant use was inversely associated with PD (odds ratio [OR]: 0.74, p-false discovery rate (FDR) = 0.016), whereas MDD itself showed no causal association (OR: 1.01, p-FDR = 0.934). MVMR confirmed that the inverse association between genetic liability to antidepressant use and PD was independent of genetic liability to MDD (OR: 0.69, p-FDR = 0.018). Colocalisation highlighted LHFPL3, KMT2E and SRPK2 at the chromosome 7q22.3 locus as shared genetic components. Furthermore, real-world FAERS data revealed that although most antidepressants (10/13) showed no significant disproportionate reporting for PD, clomipramine and mirtazapine were associated with increased reporting odds, whereas duloxetine exhibited a significant inverse reporting signal.

Conclusions: Genetic and observational evidence together support an inverse association between antidepressant use and PD. Given varying individual drug profiles, agents such as duloxetine warrant further prospective evaluation.

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抗抑郁药的使用和帕金森病的风险：药物特异性变异的总体保护作用

背景：抗抑郁药可引起锥体外系副作用，但其对帕金森病（PD）风险的影响尚不清楚。目的：我们的目的是调查抗抑郁药使用的遗传倾向性与PD之间的关系。方法：我们使用孟德尔随机化（MR）分析检查抗抑郁药使用对帕金森病的因果影响。我们进一步进行了多变量磁共振（MVMR）分析，通过考虑重度抑郁障碍（MDD）对PD的影响，确定抗抑郁药使用的遗传倾向性对PD的独立影响。美国食品和药物管理局不良事件报告系统（FAERS）数据库（2004年第一季度至2024年第二季度，5340万事件级别记录）被挖掘来评估13种抗抑郁药与PD之间的关系。共定位分析确定了抗抑郁药使用遗传倾向性和帕金森病之间共有的遗传变异。结果：MR分析显示抗抑郁药物使用的遗传倾向与PD呈负相关（比值比[OR]: 0.74， p-错误发现率(FDR) = 0.016），而MDD本身没有因果关系（OR: 1.01, p-FDR = 0.934）。MVMR证实抗抑郁药物使用的遗传倾向和PD之间的负相关独立于MDD的遗传倾向（OR: 0.69, p-FDR = 0.018）。共定位突出了染色体7q22.3位点的LHFPL3、KMT2E和SRPK2是共享的遗传成分。此外，真实的FAERS数据显示，尽管大多数抗抑郁药（10/13）对PD的报告没有显著的不成比例，但氯丙帕明和米氮平与报告的几率增加有关，而度洛西汀则表现出显著的反向报告信号。结论：遗传和观察证据共同支持抗抑郁药的使用与PD呈负相关。鉴于不同的个体药物特征，像度洛西汀这样的药物需要进一步的前瞻性评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

General Psychiatry 医学-精神病学

CiteScore

21.90

自引率

2.50%

发文量

848

期刊介绍： General Psychiatry (GPSYCH), an open-access journal established in 1959, has been a pioneer in disseminating leading psychiatry research. Addressing a global audience of psychiatrists and mental health professionals, the journal covers diverse topics and publishes original research, systematic reviews, meta-analyses, forums on topical issues, case reports, research methods in psychiatry, and a distinctive section on 'Biostatistics in Psychiatry'. The scope includes original articles on basic research, clinical research, community-based studies, and ecological studies, encompassing a broad spectrum of psychiatric interests.