What is the significance of dilated pupils in an adult or adolescent patient with a history of mental health issues taking Zoloft (sertraline)?

Dilated Pupils on Zoloft (Sertraline)

Dilated pupils in a patient taking sertraline are most commonly a benign anticholinergic side effect of the medication itself, but you must immediately assess for serotonin syndrome—a potentially life-threatening emergency that requires urgent recognition and treatment. 1, 2

Immediate Assessment Priority

Rule out serotonin syndrome first, as this is the most dangerous cause of pupillary dilation in patients on sertraline. Look for the triad of symptoms beyond just dilated pupils 3, 1, 2:

• Mental status changes: agitation, confusion, delirium, hallucinations 3, 1, 2
• Autonomic instability: tachycardia, labile blood pressure, diaphoresis, hyperthermia, flushing 3, 1, 2
• Neuromuscular hyperactivity: tremor, rigidity, myoclonus, hyperreflexia, clonus (particularly in lower extremities) 3, 1, 2

If serotonin syndrome is present, immediately discontinue sertraline and all serotonergic agents, provide supportive care with benzodiazepines for agitation, and consider cyproheptadine (12 mg initially, then 2 mg every 2 hours for continuing symptoms in adults; 0.25 mg/kg per day in pediatrics). 3, 2

Medication Review for Serotonergic Drug Interactions

Check for concomitant use of other serotonergic medications that dramatically increase serotonin syndrome risk 1, 2:

• MAOIs (including linezolid, methylene blue) 1
• Other antidepressants (SNRIs, tricyclics, trazodone) 1, 2
• Pain medications (tramadol, fentanyl) 1, 2
• Triptans for migraine 1, 2
• Lithium, buspirone, tryptophan, St. John's Wort 1, 2
• Recreational drugs (MDMA/ecstasy, cocaine, amphetamines) 2

Benign Sertraline-Related Pupillary Dilation

If serotonin syndrome features are absent, isolated pupillary dilation is a known anticholinergic effect of sertraline that does not require medication discontinuation. 1 However, you must address one critical ophthalmologic risk:

Angle-Closure Glaucoma Risk

The FDA label explicitly warns that pupillary dilation from sertraline can trigger angle-closure glaucoma in patients with anatomically narrow angles who lack a patent iridectomy. 1

• Assess for acute angle-closure symptoms: eye pain, headache, blurred vision, halos around lights, nausea/vomiting 3, 1
• Patients with pre-existing narrow angles should undergo gonioscopy and prophylactic iridectomy before continuing sertraline 3, 1
• Open-angle glaucoma is NOT a risk factor for this complication 1

If acute angle-closure is suspected, this is an ophthalmologic emergency requiring immediate referral for intraocular pressure measurement, gonioscopy, and potential laser peripheral iridotomy 3.

Management Algorithm for Isolated Pupillary Dilation

When serotonin syndrome and angle-closure glaucoma are excluded 1:

1. Reassure the patient that mild pupillary dilation is a common, benign side effect of sertraline 1
2. Continue current sertraline dose if the patient is otherwise tolerating the medication well and achieving therapeutic benefit 1
3. Advise about photosensitivity: patients may experience increased light sensitivity and should use sunglasses in bright environments 1
4. Monitor for progression: if pupillary dilation worsens or new symptoms develop, reassess for serotonin syndrome 1, 2

Common Pitfalls to Avoid

• Do not dismiss dilated pupils as trivial without systematically ruling out serotonin syndrome—this condition has an 11% mortality rate and requires immediate intervention 3, 2
• Do not assume all patients with dilated pupils on sertraline have serotonin syndrome—isolated pupillary dilation without the neuromuscular and autonomic features is typically benign 3, 1
• Do not perform dilated fundoscopic examination in patients with suspected narrow angles until after iridotomy, as this can precipitate acute angle closure 3, 1
• Do not confuse serotonin syndrome with neuroleptic malignant syndrome (NMS)—NMS develops over days (not hours), causes "lead pipe" rigidity (not hyperreflexia/clonus), and occurs with dopamine antagonists (not serotonergic agents) 3