Is Doxepin (tricyclic antidepressant) safe to prescribe in patients with glaucoma?

Doxepin Should Generally Be Avoided in Patients with Glaucoma

Doxepin is contraindicated in patients with glaucoma according to the FDA drug label, and this contraindication should be taken seriously given the risk of precipitating acute angle-closure glaucoma. 1

Type of Glaucoma Matters Critically

The risk profile differs dramatically based on glaucoma type:

Angle-Closure Glaucoma (Narrow Angles)

• Doxepin is absolutely contraindicated in patients with angle-closure glaucoma or anatomically narrow angles without a patent iridectomy. 1
• The FDA label explicitly warns that pupillary dilation from doxepin can trigger an acute angle-closure attack in susceptible patients. 1
• Tricyclic antidepressants like doxepin have documented cases of precipitating acute angle-closure glaucoma, with some cases resulting in bilateral involvement. 2, 3
• A case series documented four patients who developed acute angle-closure glaucoma after receiving routine doses of imipramine (another tricyclic antidepressant), all requiring laser iridotomy. 3

Open-Angle Glaucoma

• For patients with open-angle glaucoma, doxepin may be used with extreme caution and only under rigorous ophthalmologic supervision. 4
• The FDA notes that pre-existing glaucoma is "almost always open-angle glaucoma" and that open-angle glaucoma is not a risk factor for angle-closure glaucoma. 1
• However, all glaucoma patients on antidepressants require regular intraocular pressure monitoring with target IOP maintained at approximately 20% below baseline. 4

Mechanism of Risk

• Doxepin causes pupillary dilation through its anticholinergic effects, which can precipitate angle closure in anatomically predisposed patients. 1, 2
• Tricyclic antidepressants have weak anticholinergic activity that can trigger mydriasis and subsequent angle-closure attacks. 5, 2

Clinical Decision Algorithm

Before prescribing doxepin:

1. Determine the type of glaucoma - this is the critical decision point. 1

   • If angle-closure or narrow angles without iridectomy → Do not prescribe doxepin
   • If open-angle glaucoma → Proceed to step 2

2. For open-angle glaucoma patients:

   • Obtain baseline ophthalmologic examination documenting optic nerve status and visual field. 4
   • Establish baseline intraocular pressure measurements. 4
   • Coordinate care between psychiatry and ophthalmology, especially if glaucoma is severe or unstable. 4

3. If glaucoma type is unknown:

   • Patients should be examined by an ophthalmologist to determine if they have narrow angles and whether prophylactic iridectomy is needed. 1
   • Do not initiate doxepin until this assessment is complete.

Monitoring Requirements

If doxepin is prescribed to an open-angle glaucoma patient:

• Regular ophthalmologic follow-up with intraocular pressure monitoring is mandatory. 4
• Target IOP should remain approximately 20% lower than baseline measurements. 4
• Monitor for any signs of angle-closure (sudden eye pain, blurred vision, halos around lights, nausea). 1

Important Caveats

• The FDA contraindication for "glaucoma" in the doxepin label does not distinguish between types, creating confusion in clinical practice. 1
• Recent evidence suggests tricyclic antidepressants should be used with caution even in predisposed patients without diagnosed glaucoma. 6
• The risk extends to other tricyclic antidepressants, so this is a class effect, not unique to doxepin. 2, 6, 3

Safer Alternatives

Consider alternative antidepressants with lower anticholinergic burden if the patient has any glaucoma risk factors, though note that even SSRIs and SNRIs have rare reports of precipitating angle-closure glaucoma. 5, 2