Depression and Anxiety After Topical Carbonic Anhydrase Inhibitors

To investigate the association between topical carbonic anhydrase inhibitor (CAI) use and the development of depression and anxiety disorders in patients with glaucoma.

A retrospective, multicenter cohort study.

Glaucoma patients aged ≥40 years were identified using International Classification of Diseases-Tenth Revision codes H40-H42 and categorized into 2 groups: those prescribed topical CAIs (study group) and those with no history of CAI use (control group). Patients receiving systemic CAIs were excluded from both groups.

We analyzed deidentified patient data from the TriNetX United States Collaborative network. We performed propensity score matching (PSM) to balance demographic, ocular, and systemic covariates. Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals.

The primary outcome was new-onset depression (International Classification of Diseases-Tenth Revision F32, F33, F43.21) and initiation of antidepressant therapy within 3 months, 6 months, and 1 year of topical CAI initiation. Secondary outcomes included new-onset anxiety disorders (F41).

After PSM, new-onset depression was more frequent among topical CAI users than controls at 3 months (1.42% vs. 0.77%), 6 months (2.46% vs. 1.41%), and 1 year (4.05% vs. 2.47%; all P < 0.001). Antidepressant prescriptions were also more frequent in the CAI group at 3 months (3.57% vs. 1.28%), 6 months (5.0% vs. 2.49%), and 1 year (7.7% vs. 4.4%; all P < 0.001). Anxiety disorders occurred more often in topical CAI users across all time points (all P < 0.001). In Cox models, topical CAI use was associated with increased hazards of depression (aHR 1.36 at 3 months; 1.28 at 6 months; 1.27 at 1 year), antidepressant initiation (aHR 2.45 at 3 months; 2.03 at 6 months; 1.83 at 1 year), and anxiety disorders (aHR range 1.30-1.48; all P < 0.001).

Topical CAI use was associated with an increased risk 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.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.