What alternative antidepressant can be used instead of Cymbalta (duloxetine) and Prazosin if there is an increased pupil size in the eye?

Alternative Antidepressants for Patients with Increased Pupil Size

For patients experiencing increased pupil size (mydriasis) while taking Cymbalta (duloxetine) and prazosin, bupropion is the recommended alternative antidepressant due to its minimal effect on pupil dilation and lower risk of angle-closure glaucoma.

Understanding the Problem

• Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) that can cause mydriasis (pupil dilation) due to its adrenergic effects and serotonergic activity 1
• Prazosin, an alpha-1 adrenergic receptor antagonist commonly used for PTSD-associated nightmares, may also affect pupillary response 2, 3
• Increased pupil size (mydriasis) is concerning as it can precipitate angle-closure glaucoma in susceptible individuals 4, 5

Best Alternative Antidepressant Options

First-Line Alternative: Bupropion

• Bupropion (norepinephrine-dopamine reuptake inhibitor) has minimal serotonergic activity and therefore less risk of causing mydriasis compared to SNRIs and SSRIs 6
• Bupropion has a different mechanism of action than duloxetine, working primarily on dopamine and norepinephrine without significant serotonin effects 6
• While bupropion's label mentions angle-closure glaucoma as a potential risk, clinical evidence suggests this risk is lower than with serotonergic antidepressants 6, 7

Second-Line Alternatives: Mirtazapine or Tricyclic Antidepressants

• Mirtazapine may be considered as it has a different mechanism of action than SNRIs and has shown faster onset of action compared to SSRIs 2
• Certain tricyclic antidepressants (TCAs) with less anticholinergic properties like nortriptyline may be considered, but should be used with caution as TCAs as a class can still cause mydriasis 2, 8
• When using TCAs, careful titration starting at low doses (10 mg/day) is recommended, especially in older patients 2

Antidepressants to Avoid

• All SSRIs (fluoxetine, sertraline, paroxetine, etc.) should be avoided as they can cause mydriasis and potentially trigger angle-closure glaucoma in susceptible individuals 5, 1
• Other SNRIs like venlafaxine should be avoided as they have similar mechanisms to duloxetine and can cause pupil dilation 2, 1
• Medications with strong anticholinergic properties should be avoided as they can worsen mydriasis 8

Alternative for PTSD Nightmares (Replacing Prazosin)

• Topiramate may be considered as an alternative to prazosin for PTSD-associated nightmares 2
• Starting dose of topiramate should be low (25 mg/day) and can be gradually increased to 100 mg/day as needed 2
• Topiramate has been shown to reduce nightmares in 79% of patients with PTSD, with full suppression in 50% 2

Monitoring Recommendations

• Patients should undergo a dilated fundus examination prior to starting any new antidepressant therapy to assess for narrow angles or other risk factors for angle-closure glaucoma 4
• Regular monitoring of pupil size and intraocular pressure is recommended, especially during the initial weeks of treatment 5
• Patients should be educated about symptoms of angle-closure glaucoma (eye pain, blurred vision, seeing halos around lights, nausea) and instructed to seek immediate medical attention if these occur 4, 5

Special Considerations

• Patients with pre-existing narrow angles are at significantly higher risk for developing angle-closure glaucoma with any medication that can cause mydriasis 5
• Older patients and those with hyperopia (farsightedness) are at increased risk for angle-closure glaucoma and require extra caution 1
• Avoid combining multiple serotonergic medications due to the increased risk of serotonin syndrome 9, 4

Treatment Algorithm

1. Confirm that increased pupil size is medication-related and not due to other ocular conditions
2. Consider bupropion as first-line alternative to duloxetine
3. If bupropion is contraindicated or ineffective, consider mirtazapine
4. For PTSD nightmares, consider topiramate as an alternative to prazosin
5. Monitor pupil size and intraocular pressure regularly
6. Refer to ophthalmology for comprehensive eye examination if symptoms persist

Remember that any antidepressant can potentially affect pupil size, but bupropion carries the lowest risk among effective antidepressant options for patients experiencing mydriasis with duloxetine and prazosin.