Risk of acute angle-closure glaucoma with antidepressants

Acute angle-closure glaucoma is an ophthalmologic emergency that has been associated with specific medications, including selective serotonin reuptake inhibitors (SSRIs). SSRIs, which are commonly prescribed for mental health conditions, are believed to increase the risk of acute angle-closure glaucoma because of their weak anticholinergic effect and potential for causing mydriasis. Several case reports have shown that escitalopram, one of the most commonly prescribed SSRIs, might increase the risk of acute angle-closure glaucoma. However, it is unknown whether escitalopram has a higher risk of inducing acute angle-closure glaucoma compared with other SSRIs or other antidepressants. To examine this issue, researchers from the University of British Columbia investigated whether escitalopram has a greater risk of acute angle-closure glaucoma compared to other SSRI or non-SSRI antidepressants. A nested case-control design (a cohort design with a case-control analysis) cohort study was used. It included a random sample of 16 million patients from the IQVIA health claims database, which captured all physician visits and prescription drugs from 2006 to 2020, and demographics for all study subjects.The study included new users of citalopram, escitalopram, sertraline (a chemically unrelated SSRI) and venlafaxine (a serotonin–norepinephrine reuptake inhibitor), with a one-year look-back period to exclude prevalent users of the study drugs and previous glaucoma diagnoses. For each case of acute angle-closure glaucoma, four matched controls were identified. Current users of a study drug were defined as those that used at least one prescription of a study drug every three months in the year prior to the event date. The analysis involved sex-adjusted hazard ratios of acute angle-closure glaucoma for current users. Risk was compared among individuals on the different antidepressants, with sertraline users as the reference group. A sensitivity analysis also looked at current users for two years prior to the event date.Results showed the following:The cohort included 865,546 subjects, with 589 cases of acute angle-closure glaucoma and 2,356 controls.The distribution of antidepressant prescriptions was as follows: 41.4% for escitalopram, 24.1% for sertraline, 20.0% for venlafaxine and 14.4% for citalopram.Citalopram demonstrated a nonsignificant trend toward a 48% lower acute angle-closure glaucoma risk compared to sertraline (relative risk [RR]=0.52, 95% confidence interval [CI] 0.26–1.05).Both escitalopram (RR=0.94, 95% CI 0.61–1.44) and venlafaxine (RR=0.79, 95% CI 0.50–1.26) exhibited nonsignificant trends toward a lower risk of acute angle-closure glaucoma compared to sertraline.Additional analysis among individuals with continuous use of antidepressants (at least 1 prescription every 3 months during the last 2 years), with sertraline as the reference drug, showed a nonsignificant trend toward a 49% lower risk with citalopram (RR=0.51, 95% CI 0.25–1.05). As well, neither escitalopram (RR=0.89, 95% CI 0.57–1.41) nor venlafaxine (RR=0.87, 95% CI 0.53–1.43) exhibited statistically significant differences in acute angle-closure glaucoma risk compared to sertraline.The authors conclude that their study shows a reduced risk of acute angle-closure glaucoma with citalopram, escitalopram and venlafaxine compared to sertraline, but these trends did not reach statistical significance. These findings suggest that while escitalopram may confer a lower risk than sertraline, further research with larger cohorts is warranted. The authors believe their results underscore the importance of healthcare provider vigilance when prescribing antidepressants, particularly in patients at risk of glaucoma. Clinicians should remain attentive to ocular health considerations when prescribing antidepressants to minimize the risk of acute angle-closure glaucoma-related complications.ReferenceKhan HM, Schendel S, Mikelberg FS, et al. Acute angle-closure glaucoma risk: a comparative study of escitalopram and antidepressants. Can J Ophthalmol 2025;60(3):e469-e470. (accessed June 24, 2025).

Risk of acute angle-closure glaucoma with antidepressants

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