What are the risks of using Selective Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake Inhibitors (NRIs) in patients with glaucoma angle closure?

Risks of SSRIs and NRIs in Patients with Angle Closure Glaucoma

SSRIs and NRIs can precipitate acute angle-closure glaucoma in susceptible individuals through pupillary dilation, particularly in patients with anatomically narrow angles who do not have a patent iridectomy. 1 This risk requires careful consideration when prescribing these medications to patients with known angle closure glaucoma or those at risk.

Mechanism of Risk

• Pupillary dilation effect: SSRIs and SNRIs can cause mild pupillary dilation that may trigger an angle closure attack in anatomically predisposed individuals 1
• Anticholinergic properties: Some antidepressants, particularly those with stronger anticholinergic effects, pose greater risk for angle closure 2
• Serotonergic effects: Serotonin may play a role in intraocular pressure (IOP) control, with SSRIs potentially causing IOP modifications in some patients 3

Risk Stratification

Higher Risk Patients:

• Patients with known angle closure glaucoma
• Patients with anatomically narrow angles without patent iridectomy
• Patients with risk factors for angle closure:
  • Asian descent (particularly Chinese)
  • Hyperopia
  • Shallow anterior chamber depth
  • Short axial length
  • Thick crystalline lens
  • Steep corneal curvature
  • Older age (>50 years)
  • Female gender
  • Family history of angle closure 4, 5

Medication Risk Levels:

• Higher risk: Tricyclic antidepressants (due to stronger anticholinergic effects) 2, 6
• Moderate risk: SSRIs and SNRIs (sertraline, venlafaxine) 1, 7, 3
• Age-dependent risk: Bupropion shows nearly doubled risk (adjusted rate ratio 1.98) in patients younger than 50 years 8

Clinical Recommendations

1. For patients with diagnosed angle closure glaucoma:

   • Consider alternatives to SSRIs/NRIs when possible
   • If these medications are necessary, ensure patient has undergone definitive treatment (iridectomy) 1
   • Monitor IOP regularly during treatment

2. For patients with risk factors but no diagnosis:

   • Consider ophthalmologic evaluation before starting SSRIs/NRIs to assess angle anatomy 3
   • Educate patients about symptoms of acute angle closure (severe eye pain, blurred vision, halos around lights, headache, nausea/vomiting) 5

3. For patients already on SSRIs/NRIs:

   • Be vigilant for symptoms of angle closure, particularly during dose adjustments
   • Consider ophthalmologic follow-up for high-risk patients

Special Considerations

• Underdiagnosis concern: The incidence of SSRI-related IOP modifications is likely underestimated as many cases may be asymptomatic or present with subtle symptoms 3
• Elderly patients: May be at greater risk due to age-related anatomical changes and higher prevalence of narrow angles 3
• Combination therapy: Use caution when combining SSRIs/NRIs with other medications that can affect pupil size or IOP

Warning Signs and Management

• If a patient on SSRIs/NRIs develops eye pain, blurred vision, halos around lights, headache, nausea or vomiting, consider acute angle closure glaucoma as a possible diagnosis
• Acute angle closure is an emergency requiring immediate ophthalmologic intervention
• Without prompt treatment, approximately 18% of eyes can develop permanent vision loss following an acute attack 5

Practical Approach

1. Before prescribing SSRIs/NRIs:

   • Screen for glaucoma risk factors and history
   • Consider ophthalmologic consultation for high-risk patients

2. During treatment:

   • Inform patients about potential risk and symptoms to watch for
   • Start with lower doses in high-risk patients
   • Monitor for visual symptoms, particularly during dose adjustments

3. If angle closure is suspected:

   • Immediate ophthalmologic referral
   • Consider temporarily discontinuing the medication if appropriate

The risk of angle closure with SSRIs/NRIs, while present, should be balanced against the need for effective treatment of depression or anxiety disorders. With appropriate screening, monitoring, and patient education, these medications can often be used safely even in patients with risk factors for angle closure.