Antidepressants Associated with Lower Risk of AMD Onset and Progression

These findings suggest that antidepressants may have a protective benefit against AMD progression, providing an intriguing avenue for further investigation. Photo: Carolyn Majcher, OD. Click image to enlarge. In a recent study, researchers evaluated the association between antidepressant use and the risk of developing either non-exudative or exudative age-related macular degeneration (AMD), as well as the progression from the dry to the wet form, in patients using selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs). They found that the use of these antidepressants was associated with a lower risk of AMD onset and progression. The findings were reported last week in American Journal of Ophthalmology.Patients aged 40 years and older were identified from the TriNetX database and data from 2004 to 2023 was analyzed. Subjects were grouped based on exclusive use of SSRIs (633,535), SNRIs (826,404) or TCAs (501,873) and compared to a control group without antidepressant use. Patients using multiple antidepressant classes were excluded.Antidepressant use was associated with a significantly reduced risk of developing both forms of AMD, and patients using these meds also showed a lower likelihood of progressing from dry to wet. Potential mechanisms for these protective effects include reduced inflammation, decreased oxidative stress and neuroprotection.Previous studies have shown fluoxetine’s effects in mitigating dry AMD, finding success in oral and intraocular administrations, as well as potential delivery by intraocular implant. “Interestingly, another study found that the retinal nerve fiber layer (RNFL) thickness and CFT were significantly reduced in participants with less than one year of SSRI therapy compared to control, yet longer SSRI use showed no significant difference to the control group,” the authors wrote in their paper. “This indicates that SSRIs may influence the cellular health of the retina and choroid, specifically by means of the serotonergic and anticholinergic pathways.”The serotonergic system may be implicated in dry AMD, as it has the potential to alter retinal perfusion and lead to changes in RNFL thickness, ultimately allowing for retinal degeneration, the authors wrote. The changes in vascular tone, particularly central choroidal changes, would be implicated in wet AMD.The study authors note that “it is possible that the SSRIs—and potentially translating this to the similar antidepressants SNRis and TCAs—may have a more beneficial or protective effect on these pathways, particularly in early use of the drug,” they wrote.With SSRIs increasing the amount of serotonin available to bind to receptors, it has also been found that agonists at the 5HT1A serotonin receptor enable protection of the retina from severe photo-oxidative stress. This lessens the progression of dry AMD to wet AMD.“Similarly, SNRIs bind to 5-HT and noradrenaline transporters in order to inhibit the reuptake of serotonin in a selective manner and, in this way, they are termed as having a ‘dual mode of action.’”TCAs have also shown beneficial effects in modulating oxidative stress, as seen by the ability of amitriptyline, clomipramine and imipramine to suppress and decrease the proinflammatory cytokines Interleukin-1 beta and tumor necrosis factor alpha. This is significant, the authors noted, because oxidative damage is known to be a main cause of inflammation leading to AMD.“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,” the authors wrote in their paper.The researchers added that while the observed trends may help generate hypotheses for future research, they do not support changes in antidepressant prescribing practices.Click here for the journal source. Mahmoudzdeh R, Zaichik M, Farhani K, et al. Antidepressant use and incidene and progression of age-related macular degeneration in a National United States database. Amer J Ophthalmol. August 25, 2025. [Epub ahead of print.]This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.