What is already known on this topic

Acute angle-closure glaucoma (AACG) may cause symptoms including eye pain, changes in vision, or swelling and redness and can rapidly lead to permanent blindness if not treated.1 Medications can precipitate AACG through adrenergic or anticholinergic-mediated pupillary dilation that results in the physical obstruction of the outflow of intraocular fluid in susceptible individuals. Case reports and a previous large database study from Ontario, Canada,2 have suggested an association between new use of selective serotonin reuptake inhibitors (SSRIs) and AACG. The potential mechanism underlying this association is unclear but may be related to effects on norepinephrine or serotonin receptors in the iris and ciliary body of the eye.3

Methods of the study

This was a case–control study using a Taiwanese healthcare insurance database over an 11-year period (2000–2011). A total of 1465 AACG cases were matched on age (within 5 years), sex and calendar year to 5712 controls without AACG. Antidepressant exposure was assessed for cases and controls immediately prior to their index dates. SSRI use was categorised as immediate (within the 7 days of index for cases and controls) or non-immediate (8–30 days prior to index). SSRI dose was classified as either high dose or low dose (>20 or <20 mg mean daily dose, respectively) regardless of SSRI type.

What this paper adds

• The authors found a 5.8-fold increased risk of AACG associated with immediate use of SSRIs (OR 5.8, 95% CI 1.89 to 17.9), but no increased risk with non-immediate use of SSRIs (OR 0.67, 0.25 to 1.75) after adjusting for a limited number of confounders, including non-SSRI antidepressant use, diabetes, hypertension, hyperlipidaemia, coronary artery disease, anxiety and depression.

• Among immediate SSRI users, risk of AACG was greater in the high-dose group (OR 8.53, 1.65 to 44.0). Fluoxetine and sertraline were the most frequently prescribed antidepressants in individuals with AACG.

• This study adds additional evidence of an association of AACG with various SSRI antidepressants, particularly within the first week of initiating treatment.2

• In particular, their finding of strong association (OR 5.8, 1.89 to 17.9) and a dose–response effect points to a possible causal relationship.

• While SSRIs use can be associated with AACG, <1% of AACG were exposed to new use of SSRIs prior to developing AACG. Therefore, SSRIs are likely an uncommon cause of AACG overall.

Limitations

• The findings are limited to a known high-risk group, that is, an Asian population,1 and may not generalise to other, lower risk groups.

• The exact mechanisms underlying SSRI-related AACG remain unclear. Anticholinergic medications are known to have an effect on pupillary dilation. However, there were no AACG cases associated with paroxetine, which has the greatest anticholinergic effect among SSRIs. Therefore, it is likely that some of the mechanisms by which SSRIs may be associated with AACG may be through their effects on serotonin or other mechanisms besides anticholinergic effects.

• Medication use other than antidepressants was not extensively examined in the study and may represent an important potential confounder, given that many other classes of medications have been associated with AACG.1

What next in research

• Additional large-scale studies such as the current study in more diverse populations are needed to determine if this adverse effect is a concern among a more heterogeneous population.

• Further characterisation of differential effects between individual antidepressants is needed to determine which, if any, may be safer to use in at-risk individuals.

• Many psychotropic medications have anticholinergic, adrenergic and/or serotonergic effects, and further studies are needed to determine if the risk of AACG extends to other classes of commonly used medications.

• Whether SSRIs have any effects on open-angle glaucoma, which is a much more common cause of glaucoma, requires further study.

Do these results change your practices and why?

Yes. Ocular side effects of SSRIs are rarely recognised and have potentially serious consequences. The risk of AACG appears to be highest after initiation of SSRI treatment. At present, it is unclear whether only high-risk groups are affected by AACG, or whether this risk extends to all individuals. Regardless, the risk of AACG related to SSRIs is now the subject of updated product labelling warnings from regulatory bodies in the USA and Canada.4 ,5 Since patients are unlikely to be aware that they are at risk, prescribers should use SSRIs cautiously in those who may be more susceptible to AACG, and be vigilant if visual symptoms develop.