Antidepressant Use Linked to Lower Risk of Age-Related Macular Degeneration: Study Shows
USA: Use of common antidepressants may lower the risk of developing age-related macular degeneration (AMD) and slow its progression, according to a large U.S. database analysis.
The findings suggest that selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) could play a protective role against both non-exudative and exudative AMD, though more research is needed to confirm the link. The study has been published in the American Journal of Ophthalmology.
The investigation was led by Raziyeh Mahmoudzadeh from the Department of Ophthalmology, Virginia Commonwealth University, Richmond, Virginia, along with colleagues. Using real-world evidence, the team explored whether patients on antidepressants had a different risk profile for AMD compared with those not taking these medications.
For their analysis, the researchers used the TriNetX database, covering patients aged 40 years and older between October 2004 and October 2023. Individuals were categorized into three groups—those exclusively using SSRIs, SNRIs, or TCAs—and were compared with matched controls without antidepressant exposure. To minimize confounding, the authors applied propensity score matching that accounted for 17 variables, including age, sex, smoking status, hypertension, and cardiovascular disease. The main outcomes included the incidence of non-exudative AMD, exudative AMD, and progression from non-exudative to exudative AMD.
The key findings of the study were as follows:
- The study included over 633,000 SSRI users, 826,000 SNRI users, and about 502,000 TCA users after matching.
- SSRI use was associated with a 39% lower risk of non-exudative AMD (RR 0.606) and a 27% lower risk of exudative AMD (RR 0.733).
- SNRI use showed an 86% reduced risk of non-exudative AMD (RR 0.141) and an 84% lower risk of exudative AMD (RR 0.161).
- TCA use was linked to a 77% reduced risk of non-exudative AMD (RR 0.234) and a 73% reduced risk of exudative AMD (RR 0.267).
- Antidepressant use also reduced the risk of progression from non-exudative to exudative AMD: 30% reduction with SSRIs (RR 0.701), 34% with SNRIs (RR 0.665), and 32% with TCAs (RR 0.676).
The authors highlighted that the potential mechanisms may involve reduced systemic inflammation, decreased oxidative stress, and neuroprotective effects mediated by brain-derived neurotrophic factors, and suppression of pro-inflammatory cytokines. Since both depression and AMD share pathways of inflammation and neurodegeneration, antidepressants may inadvertently influence eye health.
However, they cautioned that these results are exploratory and hypothesis-generating. As the study was retrospective and based on observational data, causality cannot be confirmed. Prospective clinical trials and mechanistic studies will be essential to determine whether antidepressants can be recommended as part of AMD prevention strategies.
"The analysis suggests that antidepressant use is associated with a lower risk of developing and progressing AMD, offering new insights into the potential dual benefits of these medications. If confirmed in future research, antidepressants could emerge as an unexpected ally in the fight against one of the leading causes of vision loss among older adults," the authors concluded.
Reference:
Mahmoudzadeh R, et al "Antidepressant use and incidence and progression of age-related macular degeneration in a national United States database." Am J Ophthalmol 2025; DOI: 10.1016/j.ajo.2025.08.052.
