Antidepressant Use and Incidence and Progression of Age-Related Macular Degeneration in a National United States Database

IF 4.2 1区医学 Q1 OPHTHALMOLOGY

American Journal of Ophthalmology Pub Date : 2025-08-28 DOI:10.1016/j.ajo.2025.08.052

RAZIYEH MAHMOUDZADEH , MICHELLE ZAICHIK , KEAN FARHANI , MIRATAOLLAH SALABATI , JESSICA RANDOLPH

{"title":"Antidepressant Use and Incidence and Progression of Age-Related Macular Degeneration in a National United States Database","authors":"RAZIYEH MAHMOUDZADEH , MICHELLE ZAICHIK , KEAN FARHANI , MIRATAOLLAH SALABATI , JESSICA RANDOLPH","doi":"10.1016/j.ajo.2025.08.052","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the association between antidepressant use and the risk of developing nonexudative and exudative age-related macular degeneration (AMD), as well as the progression from nonexudative to exudative AMD, in patients using selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs).</div></div><div><h3>Design</h3><div>Retrospective clinical cohort study.</div></div><div><h3>Subjects</h3><div>Patients aged ≥40 years identified from the TriNetX database (October 2004-October 2023). Individuals were grouped based on exclusive use of SSRIs, SNRIs, or TCAs and compared to a control group without antidepressant use. Patients using multiple antidepressant classes were excluded.</div></div><div><h3>Methods</h3><div>Propensity score matching (PSM) was applied to adjust for 17 confounders, including age, sex, smoking status, hypertension, and cardiovascular disease. The primary outcomes were the incidence of nonexudative AMD, exudative AMD, and progression from nonexudative to exudative AMD.</div></div><div><h3>Main Outcome Measures</h3><div>Risk ratios (RRs) comparing the incidence of nonexudative AMD, exudative AMD, and AMD progression in each antidepressant group versus matched controls.</div></div><div><h3>Results</h3><div>After PSM, the analysis included 633 535 SSRI users, 826 404 SNRI users, and 501 873 TCA users. Compared to controls, antidepressant use was associated with a significantly reduced risk of nonexudative AMD (RR 0.606 for SSRIs; 0.141 for SNRIs; 0.234 for TCAs), exudative AMD (RR 0.733 for SSRIs; 0.161 for SNRIs; 0.267 for TCAs), and progression to exudative AMD (RR 0.701 for SSRIs; 0.665 for SNRIs; 0.676 for TCAs).</div></div><div><h3>Conclusions</h3><div>Use of SSRIs, SNRIs, or TCAs was associated with a lower risk of AMD onset and progression. Potential mechanisms include reduced inflammation, decreased oxidative stress, and neuroprotection via upregulation of brain-derived neurotrophic factors and suppression of proinflammatory cytokines. These findings are exploratory and hypothesis-generating, and further prospective and mechanistic studies are needed to better understand the relationship between antidepressant use and AMD pathophysiology.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"280 ","pages":"Pages 458-471"},"PeriodicalIF":4.2000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0002939425004660","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

To evaluate the association between antidepressant use and the risk of developing nonexudative and exudative age-related macular degeneration (AMD), as well as the progression from nonexudative to exudative AMD, in patients using selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs).

Design

Retrospective clinical cohort study.

Subjects

Patients aged ≥40 years identified from the TriNetX database (October 2004-October 2023). Individuals were grouped based on exclusive use of SSRIs, SNRIs, or TCAs and compared to a control group without antidepressant use. Patients using multiple antidepressant classes were excluded.

Methods

Propensity score matching (PSM) was applied to adjust for 17 confounders, including age, sex, smoking status, hypertension, and cardiovascular disease. The primary outcomes were the incidence of nonexudative AMD, exudative AMD, and progression from nonexudative to exudative AMD.

Main Outcome Measures

Risk ratios (RRs) comparing the incidence of nonexudative AMD, exudative AMD, and AMD progression in each antidepressant group versus matched controls.

Results

After PSM, the analysis included 633 535 SSRI users, 826 404 SNRI users, and 501 873 TCA users. Compared to controls, antidepressant use was associated with a significantly reduced risk of nonexudative AMD (RR 0.606 for SSRIs; 0.141 for SNRIs; 0.234 for TCAs), exudative AMD (RR 0.733 for SSRIs; 0.161 for SNRIs; 0.267 for TCAs), and progression to exudative AMD (RR 0.701 for SSRIs; 0.665 for SNRIs; 0.676 for TCAs).

Conclusions

Use of SSRIs, SNRIs, or TCAs was associated with a lower risk of AMD onset and progression. Potential mechanisms include reduced inflammation, decreased oxidative stress, and neuroprotection via upregulation of brain-derived neurotrophic factors and suppression of proinflammatory cytokines. These findings are exploratory and hypothesis-generating, and further prospective and mechanistic studies are needed to better understand the relationship between antidepressant use and AMD pathophysiology.

查看原文本刊更多论文

美国国家数据库中抗抑郁药的使用和年龄相关性黄斑变性的发病率和进展。

目的：评估使用选择性5 -羟色胺再摄取抑制剂（SSRIs）、5 -羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）或三环抗抑郁药（TCAs）的患者，抗抑郁药的使用与发生非渗出性和渗出性年龄相关性黄斑变性（AMD）的风险之间的关系，以及从非渗出性到渗出性AMD的进展。设计：回顾性临床队列研究。受试者：从TriNetX数据库中确定的年龄≥40岁的患者（2004年10月- 2023年10月）。个体根据单独使用SSRIs、SNRIs或TCAs进行分组，并与不使用抗抑郁药的对照组进行比较。使用多种抗抑郁药物的患者被排除在外。方法：采用倾向评分匹配（PSM）对年龄、性别、吸烟状况、高血压、心血管疾病等17个混杂因素进行校正。主要结果是非渗出性AMD、渗出性AMD的发生率，以及从非渗出性AMD向渗出性AMD的进展。主要结局指标：风险比（rr）比较每个抗抑郁药组与匹配对照组的非渗出性AMD、渗出性AMD和AMD进展的发生率。结果：PSM后，分析包括633,535名SSRI使用者，826,404名SNRI使用者和501,873名TCA使用者。与对照组相比，抗抑郁药的使用与非渗出性AMD （SSRIs的RR为0.606，SNRIs的RR为0.141，TCAs的RR为0.234）、渗出性AMD （SSRIs的RR为0.733，SNRIs的RR为0.161，TCAs的RR为0.267）和进展为渗出性AMD （SSRIs的RR为0.701，SNRIs的RR为0.665，TCAs的RR为0.676）的风险显著降低相关。结论：使用SSRIs、SNRIs或TCAs与AMD发病和进展的风险较低相关。潜在的机制包括减少炎症，减少氧化应激，以及通过上调脑源性神经营养因子和抑制促炎细胞因子来保护神经。这些发现是探索性和假设性的，需要进一步的前瞻性和机制研究来更好地了解抗抑郁药使用与AMD病理生理之间的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

American Journal of Ophthalmology 医学-眼科学

CiteScore

9.20

自引率

7.10%

发文量

406

审稿时长

36 days

期刊介绍： The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations, and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented online at www.AJO.com and on ScienceDirect. The American Journal of Ophthalmology publishes Full-Length Articles, Perspectives, Editorials, Correspondences, Books Reports and Announcements. Brief Reports and Case Reports are no longer published. We recommend submitting Brief Reports and Case Reports to our companion publication, the American Journal of Ophthalmology Case Reports. Manuscripts are accepted with the understanding that they have not been and will not be published elsewhere substantially in any format, and that there are no ethical problems with the content or data collection. Authors may be requested to produce the data upon which the manuscript is based and to answer expeditiously any questions about the manuscript or its authors.