Can sertraline (selective serotonin reuptake inhibitor) or Adderall (mixed amphetamine salts) cause mydriasis?

Can Sertraline or Adderall Cause Dilated Pupils?

Yes, both sertraline and Adderall (amphetamine) can cause mydriasis (dilated pupils), though through different mechanisms and with different clinical significance.

Adderall (Amphetamine) and Mydriasis

Amphetamine consistently causes pupillary dilation through both central and peripheral mechanisms, making mydriasis a characteristic and expected effect. 1, 2

• Amphetamine produces mydriasis primarily through central nervous system inhibition of tonic outflow from the oculomotor nucleus (parasympathetic inhibition), with a minor contribution from peripheral sympathomimetic effects 2
• The mydriatic effect involves both alpha-adrenergic peripheral sympathetic action and central dopaminergic mechanisms 1
• This pupillary dilation is dose-dependent and represents a reliable clinical sign of amphetamine use 1

Sertraline (SSRI) and Mydriasis

Sertraline and other SSRIs cause mydriasis that is persistent throughout treatment, though the clinical significance is generally limited in patients with open-angle anatomy. 3, 4

• SSRIs including sertraline produce statistically significant pupillary dilation (mean pupil diameter 3.53 mm in SSRI users versus 3.11 mm in controls, p<0.05) that persists regardless of treatment duration 3
• The mydriatic effect is independent of whether patients receive SSRIs for less than 6 months or longer than 6 months 3
• This mydriasis is part of the broader serotonergic effects on autonomic function 4

Critical Clinical Caveat: Angle-Closure Risk

The most important clinical concern is that both medications can precipitate angle-closure glaucoma in anatomically predisposed patients. 4

• SSRIs including sertraline may add risk for angle-closure glaucoma, but only in eyes with narrow angles 4
• Tricyclic antidepressants cause angle closure in all patients with narrow angles, whereas SSRIs pose lower but still present risk 4
• In open-angle eyes, SSRIs actually decrease intraocular pressure (16.04-16.11 mmHg versus 17.34 mmHg in controls, p<0.05) 3

Serotonin Syndrome Consideration

Mydriasis is one component of serotonin syndrome, which can occur with sertraline, particularly when combined with other serotonergic agents. 5

• Serotonin syndrome in adults includes autonomic hyperactivity with mydriasis, along with fever, tachycardia, tachypnea, diaphoresis, mental status changes, and neuromuscular abnormalities (tremor, clonus, hyperreflexia, hypertonia) 5
• This represents a potentially life-threatening complication requiring immediate cessation of all serotonergic agents 6

Practical Implications

• Amphetamine-induced mydriasis is expected, consistent, and can serve as an objective marker of drug effect 1, 2
• Sertraline-induced mydriasis is milder but persistent, and generally well-tolerated in patients without narrow-angle anatomy 3
• Screen patients for narrow-angle glaucoma risk factors before initiating either medication, particularly SSRIs 4
• If acute angle-closure symptoms develop (eye pain, halos around lights, headache, nausea), discontinue the medication and refer emergently to ophthalmology 4