Can Quetiapine, Clonazepam, Mirtazapine, and Gabapentin cause dry eye?

Medications and Dry Eye Risk

Yes, quetiapine, clonazepam, mirtazapine, and gabapentin can all cause or worsen dry eye disease through anticholinergic and other mechanisms that disrupt tear production and ocular surface homeostasis. 1, 2, 3

Mechanism of Dry Eye from These Medications

Anticholinergic and Antianxiety Effects

• Quetiapine (antipsychotic), clonazepam (benzodiazepine), and mirtazapine (antidepressant) all possess anticholinergic properties that disrupt the efferent cholinergic nerves responsible for stimulating tear secretion. 2, 4
• Antidepressant and antianxiety medications are specifically identified as risk factors for dry eye disease in the Beaver Dam Eye Study, one of the largest population-based studies on this topic. 1, 2, 4
• Benzodiazepines like clonazepam contribute through both anticholinergic effects and potential associations with sleep disorders, which independently increase dry eye risk. 4

Gabapentin's Unique Role

• Gabapentin does not typically cause dry eye but is actually used to treat neuropathic ocular pain that often accompanies severe dry eye disease. 5
• In patients with severe dry eye and neuropathic pain component, gabapentin combined with artificial tears and cyclosporine showed significantly better improvement in symptoms and objective measures compared to artificial tears and cyclosporine alone. 5

Additive Medication Effects

• Patients taking multiple medications from your list face compounded risk, as these drugs create an additive effect on dry eye symptoms. 4
• The combination of antipsychotics, benzodiazepines, and antidepressants is particularly problematic as all share anticholinergic mechanisms. 3, 6

Clinical Recognition and Assessment

Key Symptoms to Identify

• Fluctuating vision that worsens throughout the day 4
• Ocular irritation symptoms including burning, foreign body sensation, and excessive tearing (paradoxical reflex tearing) 7
• Difficulty with reading or prolonged visual tasks due to unstable tear film 7

Objective Findings

• Punctate epithelial erosions visible on fluorescein or lissamine green staining 4
• Reduced tear break-up time (TBUT) and Schirmer test values 5
• Cloudy or blurred vision from corneal epithelial damage 7

Management Algorithm

First-Line Interventions

• Initiate preservative-free artificial tears, as preserved drops used more than 4 times daily paradoxically worsen symptoms through corneal epithelial breakdown. 4
• Implement environmental modifications: humidifiers, reduced screen time, avoiding direct air flow to eyes. 7
• Consider whether medication dosage reduction is feasible, as some dry eye effects are dose-dependent. 3

When Conservative Measures Fail

• Consider punctal occlusion or other tear conservation approaches for moderate-to-severe cases. 7
• Add topical cyclosporine for patients with inflammatory component. 5
• For patients with neuropathic ocular pain component (identified by painDETECT questionnaire), gabapentin 300-900mg daily provides significant additional benefit beyond standard dry eye treatments. 5

Medication Review Strategy

• Evaluate whether alternative medications within the same therapeutic class might have less anticholinergic burden. 3
• Recognize that completely discontinuing these medications may not be feasible given their psychiatric indications, so symptomatic dry eye management becomes essential. 3

Mandatory Ophthalmology Referral Criteria

Refer immediately to ophthalmology if any of the following occur: 7, 4

• Moderate or severe eye pain
• Lack of response to over-the-counter lubricating drops after 2-4 weeks
• Corneal infiltration or ulceration
• Progressive conjunctival scarring
• Progressive worsening of vision
• Symptoms significantly impacting quality of life or ability to perform daily activities

Critical Pitfalls to Avoid

• Do not assume gabapentin is causing dry eye—it is therapeutic for neuropathic ocular pain, not causative. 5
• Avoid prescribing preserved artificial tears for frequent use (>4 drops daily), as benzalkonium chloride causes corneal epithelial breakdown. 2, 4
• Do not overlook the cumulative anticholinergic burden when patients are on multiple medications from this list. 4, 3
• Recognize that dry eye from these medications is often chronic and requires ongoing management rather than expecting resolution while continuing the medications. 3