Which antidepressant medications are not associated with an increased risk of glaucoma?

Antidepressants Not Associated with Increased Glaucoma Risk

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are not associated with increased glaucoma risk and may actually be protective, making them the preferred antidepressant choices for patients with glaucoma or at risk for glaucoma. 1, 2, 3

Evidence-Based Recommendations by Antidepressant Class

Safe Options (No Increased Risk)

SSRIs are the most strongly supported safe option:

• Meta-analysis shows SSRIs are associated with reduced glaucoma risk (OR = 0.832,95% CrI: 0.753-0.921) 1
• SSRIs demonstrate lower intraocular pressure (IOP) compared to non-users (Hedges' g = -0.332) 1
• Large database study confirms SSRIs reduce risk of advanced primary open-angle glaucoma requiring procedures (OR = 0.70,95% CI: 0.64-0.76) 3
• Citalopram shows particularly strong protective association (OR = 0.66) 3

SNRIs also appear safe:

• No evidence of increased glaucoma risk 4
• Associated with lower IOP similar to SSRIs 2
• Can be used without concern in glaucoma patients 4

Medications Requiring Caution or Avoidance

Tricyclic antidepressants (TCAs):

• Should be avoided in glaucoma patients 4
• Anticholinergic properties can precipitate angle closure
• While one meta-analysis showed non-significant association (OR = 1.466,95% CrI: 0.700-3.338) 1, the anticholinergic mechanism and clinical practice guidelines support avoidance 4

Bupropion (contained in naltrexone ER/bupropion ER):

• Should be used with caution in glaucoma patients 5
• Guidelines specifically state naltrexone ER/bupropion ER should be used cautiously in patients with glaucoma history or risk 5

Topiramate:

• Absolutely contraindicated in glaucoma patients 5, 6
• Strong association with acute angle-closure glaucoma (OR = 3.930,95% CrI: 1.784-11.465) 1
• Multiple case reports of acute bilateral angle closure 5
• Risk highest in first month of use (>7-fold increased risk) 5

Other Antidepressants

Benzodiazepines (anxiolytics, not technically antidepressants):

• Should be avoided - significantly increased glaucoma risk (OR = 1.550,95% CrI: 1.436-1.674) 1
• Consistent effect across both short- and long-acting formulations 1

MAOIs and tetracyclic antidepressants:

• May actually be associated with decreased cataract risk 7
• Limited data on glaucoma specifically, but older literature suggests acceptable safety with monitoring 8

Clinical Algorithm for Antidepressant Selection in Glaucoma Patients

1. First-line choice: SSRIs (particularly citalopram, sertraline, fluoxetine, escitalopram)
2. Second-line choice: SNRIs (venlafaxine, duloxetine)
3. Use with caution: Bupropion (requires ophthalmologic monitoring)
4. Avoid completely:
   • Topiramate-containing medications
   • Tricyclic antidepressants
   • Benzodiazepines (if used for anxiety/depression)

Important Clinical Caveats

• The protective effect of SSRIs appears related to pupillary dilation (Hedges' g = 0.681) 2, which may reduce pupillary block risk in angle-closure mechanisms
• Patients on any antidepressant with glaucoma should remain under strict ophthalmologic supervision 4
• For patients requiring topiramate for other indications (e.g., seizures, migraines), risk is highest in the first month of therapy 5
• The association between calcium channel blockers and increased glaucoma risk (OR = 1.26) 3 should be considered when managing comorbid conditions