The risk of glaucoma and serotonergic antidepressants: A systematic review and meta-analysis

Abstract

Background: The aim of current study was to conduct a systematic review and meta-analysis to explore the relationship between antidepressant use and glaucoma. Methods: Eight major electronic databases were searched from inception until March 19th, 2018 to obtain relevant studies that evaluated associations of antidepressants [including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)] treatment and the risk of primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) as well as intraocular pressure (IOP), and related anterior chamber parameters compared to participants not exposed to antidepressant treatment. A random-effects meta-analysis was conducted. Results: Six case-control studies and one cohort study were eligible (N = 801,754). The use of SSRIs was not associated with a higher risk of glaucoma (k = 7, pooled adjusted odds ratio (pAOR) = 0.956, 95% confidence interval (CI) = 0.807 to 1.133, p = 0.604). In addition, IOP was lower in participants exposed to antidepressants (SSRIs and SNRIs) (k = 4, Hedges’ g = -0.519, 95% CI = -0.743 to -0.296, p < 0.001). Finally, pupillary diameter was higher in participants exposed to antidepressant treatment (k = 4, Hedges’ g = 0.681, 95% CI = 0.462 to 0.900, p < 0.001). Limitations: High heterogeneity of included studies limit the establishment of causal inferences. Conclusions: This meta-analysis indicates that a putative association between the use of SSRIs and a higher risk of glaucoma remains to be proven. However, antidepressant drug treatment may be associated with significantly lower IOP and higher pupillary diameter. The mechanisms underpinning these associations deserve further investigation.