​​Topical CAI Use Linked to Increased Risk of Depression and Anxiety

The mechanisms underlying CAI-associated depression remain incompletely understood, but a recent study found a significant association between topical CAI use and an elevated hazard of developing depression, initiating antidepressant therapy and experiencing anxiety disorders within the first year of treatment. These findings highlight the importance of monitoring neuropsychiatric adverse effects in glaucoma patients receiving topical CAIs. Photo: Getty Images. Many topical and systemic IOP-lowering agents are currently available in glaucoma management. Carbonic anhydrase inhibitors (CAIs) aren’t first-line therapy but are used adjunctively in a number of cases. Although rare, depressive episodes have been reported with topical CAI use and are listed as uncommon adverse effects in product labeling. However, the current evidence—limited to case reports and product information—remains insufficient to establish a causal relationship or guide clinical practice. To address this knowledge gap, researchers recently accessed a large, multicenter database to investigate the association between topical CAI therapy and the development of depression and anxiety in patients with glaucoma.In their study, which was published in Ophthalmology Science, the team determined a robust association between topical CAI use and increased risk of depression, antidepressant initiation and anxiety within the first year of treatment in these patients.“These findings underscore the importance of considering systemic and psychiatric implications when prescribing CAIs, particularly in vulnerable populations such as those with impaired renal function,” the study authors wrote in their paper. “Greater awareness of potential neuropsychiatric adverse effects may enable clinicians to balance IOP control with overall patient well-being.”The study analyzed de-identified patient data from the TriNetX United States Collaborative network. It categorized patients aged 40 and older into two groups: those prescribed topical CAIs (study group) and those with no history of CAI use (control group). After propensity score matching, both cohorts included 8,862 patients, and the mean age at prescription was 72.4 and 73.5, respectively. The primary outcome was new-onset depression and initiation of antidepressant therapy within three months, six months and one year of topical CAI initiation. Secondary outcomes included new-onset anxiety disorders.The incidence of depression was higher among topical CAI users than controls at three months (1.42% vs. 0.77%), six months (2.46% vs. 1.41%) and one year (4.05% vs. 2.47%). Antidepressant prescriptions were also more frequent in the CAI group at three months (3.57% vs. 1.28%), six months (5 % vs. 2.49%) and one year (7.7% vs. 4.4%). Anxiety disorders occurred more often in topical CAI users across all time points.In Cox models, topical CAI use was associated with increased hazard ratios for depression, as follows: 1.36 at three months; 1.28 at six months; 1.27 at one year), antidepressant initiation (2.45 at three months; 2.03 at six months; 1.83 at one year), and anxiety disorders (range 1.3 to 1.8).According to the researchers, a key limitation of their analysis was that the TriNetX database, similar to most currently available large real-world databases, does not provide granular ophthalmic data such as visual acuity, visual field indices, IOP measurements, retinal nerve fiber layer thickness or detailed imaging parameters.“As a result, we were unable to adjust for glaucoma severity, which may influence the risk of depression and anxiety independent of medication exposure,” they added. “Another limitation is the one-year median follow-up time period. Psychiatric conditions, including depression and anxiety, may emerge beyond the first year of medication exposure; therefore, our estimates may underrepresent later-onset outcomes.”The study proposed that the hazard ratios observed in this study may be conservative, and longer-term follow-up could potentially reveal stronger associations. Future studies with extended longitudinal data could be important to better characterize the temporal relationship between topical CAI use and neuropsychiatric events.Click here for the journal source. Elhusseiny AM, Alzein AF, Medeiros FA. Depression and anxiety following topical carbonic anhydrase inhibitors. Ophthalmol Sci. February 2, 2026. [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.