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

Abstract

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