What is the most appropriate first-line antidepressant for a patient with glaucoma?

Best Antidepressant for Glaucoma Patients

Selective serotonin reuptake inhibitors (SSRIs) such as sertraline are the safest first-line antidepressants for patients with glaucoma, as they carry the lowest risk of precipitating angle-closure glaucoma compared to other antidepressant classes.

Primary Recommendation: SSRIs (Sertraline)

• SSRIs like sertraline should be the preferred first-line antidepressant in glaucoma patients because they have a more favorable safety profile regarding angle-closure risk compared to other antidepressant classes 1
• The FDA labeling for sertraline warns about angle-closure glaucoma as a class effect but does not contraindicate its use in glaucoma patients, only cautioning that pupillary dilation may trigger angle-closure in patients with anatomically narrow angles who lack a patent iridectomy 1
• This makes SSRIs appropriate for patients with controlled open-angle glaucoma or those who have undergone iridectomy 1

Antidepressants to AVOID in Glaucoma Patients

Bupropion (Wellbutrin) - Use with Extreme Caution

• Bupropion carries a nearly 2-fold increased risk of angle-closure glaucoma in patients younger than 50 years (adjusted rate ratio 1.98,95% CI 1.02-3.84) 2
• The FDA label explicitly warns that bupropion can trigger angle-closure attacks in patients with anatomically narrow angles who lack a patent iridectomy 3
• Bupropion is listed in diabetes management guidelines as contraindicated in patients with acute angle-closure glaucoma when used in combination formulations (naltrexone/bupropion) 4
• Avoid bupropion entirely in glaucoma patients, particularly those under 50 years of age or with narrow angles 3, 2

Venlafaxine (Effexor) - Contraindicated

• Venlafaxine is absolutely contraindicated in patients with uncontrolled narrow-angle glaucoma according to FDA labeling 5
• The FDA label explicitly states: "Do not take venlafaxine HCl if you have uncontrolled narrow-angle glaucoma" 5
• Venlafaxine causes pupillary dilation (mydriasis), which can precipitate angle-closure attacks 5
• This is a hard contraindication—do not prescribe venlafaxine to any patient with glaucoma unless their narrow-angle glaucoma is controlled (e.g., post-iridectomy) 5

Clinical Algorithm for Antidepressant Selection

Step 1: Determine Glaucoma Type and Control Status

• Identify whether the patient has open-angle glaucoma (most common, 90% of cases) or narrow-angle glaucoma 6, 7
• Confirm current intraocular pressure (IOP) control and whether the patient has undergone iridectomy 4
• Patients with controlled open-angle glaucoma have more antidepressant options than those with narrow-angle disease 1, 7

Step 2: First-Line Choice

• Prescribe an SSRI (sertraline 50-200 mg daily) as first-line therapy for depression in glaucoma patients 1
• SSRIs carry the lowest risk profile for precipitating angle-closure compared to other antidepressant classes 1
• Monitor for serotonin syndrome if the patient is on other serotonergic medications 1

Step 3: If SSRIs Are Ineffective or Not Tolerated

• Consider tricyclic antidepressants (TCAs) with caution, as they have anticholinergic effects that can cause mydriasis 7
• Avoid bupropion and venlafaxine entirely due to documented glaucoma risks 3, 5, 2
• Consult with the patient's ophthalmologist before switching to alternative antidepressant classes 8, 9

Essential Monitoring Requirements

• All glaucoma patients on antidepressants require rigorous ophthalmologic supervision with regular IOP monitoring 8, 9
• Target IOP should be maintained at approximately 20% below baseline measurements to prevent glaucomatous damage 10, 8
• Baseline ophthalmologic examination documenting optic nerve status and visual field is recommended before initiating antidepressant therapy 8
• For patients with severe or unstable glaucoma, consultation between psychiatry and ophthalmology is advisable before starting antidepressants 8

Critical Pitfalls to Avoid

• Never prescribe venlafaxine to patients with uncontrolled narrow-angle glaucoma—this is an absolute FDA contraindication 5
• Do not assume all antidepressants carry equal risk; bupropion has nearly double the risk of angle-closure in younger patients compared to other agents 2
• Avoid combination products containing bupropion (such as naltrexone/bupropion for weight loss) in glaucoma patients, as these carry explicit warnings about acute angle-closure glaucoma 4
• Do not overlook medication-induced glaucoma risk factors; anticholinergics, certain antidepressants, and topiramate can all predispose patients to glaucoma 7
• Ensure patients understand the importance of adherence to both their glaucoma medications and antidepressant therapy, as poor adherence is common and can lead to disease progression 9

Special Considerations for Narrow-Angle Glaucoma

• Patients with anatomically narrow angles who have not undergone iridectomy are at highest risk for medication-induced angle-closure 3, 1
• If a patient with narrow-angle glaucoma requires antidepressant therapy, coordinate with ophthalmology to consider prophylactic laser peripheral iridotomy before starting treatment 1
• Even SSRIs can trigger angle-closure in susceptible patients, though the risk is lower than with other antidepressant classes 1