Safest Antidepressant in Glaucoma
SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are the safest antidepressants for patients with glaucoma, with the best evidence supporting their lack of association with increased intraocular pressure or glaucoma risk. 1
Primary Recommendation
- SSRIs and SNRIs should be the first-line antidepressants in glaucoma patients because they have the strongest evidence demonstrating no association with glaucoma or elevated intraocular pressure 1
- These agents are preferred over all other antidepressant classes when treating depression in patients with existing glaucoma or narrow angles 1
Antidepressants to AVOID
High-Risk Agents (Contraindicated)
- Tricyclic antidepressants (TCAs) must be avoided in glaucoma patients, as they carry significant risk of precipitating acute angle-closure glaucoma through their anticholinergic effects causing mydriasis 2, 1, 3
- TCAs also show increased cataract risk in pharmacovigilance data (ROR = 1.31-12.81) 4
- Tetracyclic antidepressants should be avoided despite lower cataract risk, due to their anticholinergic properties 1
Moderate-Risk Agents (Use with Extreme Caution)
- SNRIs like duloxetine and venlafaxine have case reports of precipitating bilateral acute angle-closure glaucoma, particularly in patients with anatomic predisposition (high hyperopia, narrow angles) 5, 3
- The mechanism involves mydriasis from adrenergic effects and weak anticholinergic activity 5
- However, the overall class evidence for SNRIs remains favorable compared to other antidepressants 1
Other Agents to Avoid
- Topiramate (used for depression/mood stabilization) should be avoided as it causes acute angle-closure glaucoma through ciliary body edema with anterior rotation of the iris-lens diaphragm, and iridotomy is NOT effective for this mechanism 1, 3
- Benzodiazepines should be avoided in glaucoma patients 1
Clinical Algorithm
Step 1: Assess Glaucoma Type and Risk
- Determine if patient has open-angle glaucoma (safer) versus narrow angles or angle-closure glaucoma (higher risk) 2, 3
- Patients with narrow angles are at highest risk for drug-induced acute angle-closure 3
Step 2: Select Antidepressant
- First choice: SSRIs (fluoxetine, sertraline, citalopram, escitalopram) - best safety profile 1
- Second choice: SNRIs (duloxetine, venlafaxine) - generally safe but monitor closely in narrow-angle patients 1
- Avoid entirely: TCAs, tetracyclics, topiramate, benzodiazepines 1, 3
Step 3: Pre-Treatment Assessment
- Obtain baseline ophthalmologic examination documenting optic nerve status and visual field before initiating therapy 6
- For severe or unstable glaucoma, coordinate consultation between psychiatry and ophthalmology 6
Step 4: Monitoring Protocol
- All glaucoma patients on antidepressants require rigorous ophthalmologic supervision with regular IOP monitoring 6, 7
- Target IOP should be maintained approximately 20% lower than baseline measurements 6
- Monitor for acute symptoms: eye pain, blurred vision, halos around lights, headache, nausea (signs of acute angle-closure) 5, 3
Critical Pitfalls to Avoid
- Do not assume "glaucoma" contraindications in package inserts specify which type - most do not differentiate between open-angle and angle-closure glaucoma 2
- Do not rely on iridotomy alone for protection - sulfa-based drugs and topiramate cause angle-closure through ciliary body mechanisms that iridotomy cannot prevent 3
- Do not overlook anatomic risk factors - patients with high hyperopia or narrow angles are at exponentially higher risk even with "safer" agents 5, 3
- Bilateral involvement can occur - drug-induced angle-closure often affects both eyes and can cause blindness if not recognized early 2
Special Considerations
First-Generation Antipsychotics
- If antipsychotic augmentation is needed, first-generation antipsychotics appear to have no correlation with increased IOP, though ziprasidone requires special attention 1