Effects of selective serotonin reuptake inhibitors on glaucoma: A nationwide population-based study

PLoS One. 2017 Mar 3;12(3):e0173005. doi: 10.1371/journal.pone.0173005. eCollection 2017.


Background: Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed classes of antidepressants. Glaucoma is the second leading cause of blindness globally and iatrogenic glaucoma has been implicated across disparate medication classes. Available studies that have sought to determine the association between SSRI exposure and glaucoma have provided mixed results. The aim of the study herein was to investigate whether an association exists between SSRI exposure and glaucoma incidence.

Methods: Glaucoma cases were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of glaucoma between 1997 and 2009. The date wherein the cases were diagnosed with glaucoma was operationalized as the index date. The control group was comprised of individuals within the database who were not diagnosed with glaucoma. 15,865 glaucoma cases were compared to 77,014 sex-, age-, residence- and insurance premium-matched controls on measures of prescribed duration and dosage of SSRIs up to 365 days before index date to proxy SSRIs exposure.

Results: Individuals receiving SSRIs were at greater risk of glaucoma incidence (OR = 1.39; 95% CI = 1.29-1.50); the foregoing increased likelihood was reduced after adjusting for confounding variables (aOR = 1.09; 95% CI = 1.00,1.18). SSRI treatment of longer duration (i.e. >365 days) and higher doses (≥1 defined daily dose) were associated with greater risk of glaucoma incidence (aOR = 1.36; 95% CI = 1.08-1.71). Subgroup analysis showed that the effect of SSRIs on glaucoma was limited to individuals younger than 65 years of age (aOR = 1.37; 95% CI = 1.25-1.50), without diabetes (aOR = 1.39; 95% CI = 1.27-1.52), without hypertension (aOR = 1.46; 95% CI = 1.31-1.63) or hypercholesterolemia (aOR = 1.35; 95% CI = 1.23-1.48).

Conclusion: Treatment with SSRIs was associated with greater risk of having a diagnosis of glaucoma, particularly in individuals with longer duration and/or higher average dose of SSRI. Our findings suggest that individuals receiving SSRIs treatment for extended periods of time and/or at relatively higher therapeutic doses should be monitored for symptoms associated with glaucoma.

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects*
  • Case-Control Studies
  • Databases, Factual
  • Depression / drug therapy*
  • Depression / physiopathology
  • Female
  • Glaucoma / chemically induced*
  • Glaucoma / diagnosis
  • Glaucoma / epidemiology
  • Glaucoma / pathology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Taiwan / epidemiology


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors

Grants and funding

VC-HC has received grant (CMRPG6E0271) from Chang Gung Memorial Hospital and the Ministry of Science and Technology, Taiwan (NSC 102-2314-B- 040-004-MY3). M-HN has received a grant (DOH103-HO-1113) from Tsaotun Psychiatric Center, Ministry of Health and Welfare, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.