What antidepressants cause anisocoria?

October 10, 2025 •

4 min read

While millions use antidepressants safely, a small number of people may experience unexpected side effects, including anisocoria. So, what antidepressants cause anisocoria, an uncommon but notable condition where one pupil is a different size from the other? This article delves into the specific types of antidepressants involved and the mechanisms behind this rare ocular side effect.

Quick Summary

Pharmacologic anisocoria can be a rare side effect of certain antidepressants, including SSRIs and TCAs, due to their effects on neurotransmitters. The condition results in unequal pupil sizes and requires medical evaluation to rule out serious underlying causes.

Key Points

SSRIs can cause anisocoria: Case reports have linked specific SSRIs like sertraline, citalopram, and escitalopram to pharmacologic anisocoria, an unequal pupil size.
TCAs are known to cause mydriasis: Older tricyclic antidepressants have anticholinergic properties that can lead to pupil dilation (mydriasis), which may manifest as anisocoria.
Mechanism involves neurotransmitter imbalance: Antidepressants can cause changes in pupil size by affecting neurotransmitters like serotonin and acetylcholine, which regulate the eye's pupillary muscles.
Unilateral sensitivity is a factor: Anisocoria can occur if one eye exhibits a greater sensitivity or different response to the antidepressant's effects compared to the other eye.
Medical evaluation is crucial: Sudden-onset anisocoria, especially if accompanied by other symptoms like headache or vision changes, requires immediate medical attention to rule out a serious neurological condition.
The effect is often reversible: In many documented instances, the anisocoria resolved after the patient discontinued the medication, underscoring the importance of consulting a doctor for any medication adjustments.

What is Anisocoria?

Anisocoria is a condition defined as unequal pupil sizes. The pupils, the black circular openings in the center of the iris, naturally dilate in low light and constrict in bright light to control how much light enters the eye. This process is managed by the autonomic nervous system, which controls involuntary bodily functions.

Most cases of anisocoria are benign and can be categorized into four main types:

Physiologic anisocoria: This is a harmless condition affecting up to 20% of the population, where the pupils naturally differ in size by a small amount (typically less than one millimeter).
Pathologic anisocoria: This results from an underlying disease or condition, such as Horner's syndrome or inflammation of the iris (iritis).
Mechanical anisocoria: This occurs due to trauma or other physical damage to the eye or iris structure.
Pharmacologic anisocoria: This is caused by certain medications, which is the focus of this article.

How Antidepressants Affect the Pupils

The eye's pupil size is controlled by two opposing muscles in the iris: the sphincter pupillae (which constricts the pupil) and the dilator pupillae (which dilates it). This delicate balance is influenced by the autonomic nervous system and its various neurotransmitters.

Antidepressants can interfere with this balance in several ways, leading to mydriasis (pupil dilation) or, in rare cases, anisocoria. The potential for unequal dilation can arise if there is a difference in the nervous system's response or sensitivity between the two eyes.

Serotonergic effects (SSRIs and SNRIs)

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) work by increasing serotonin levels in the brain. Serotonin receptors are also present in the eye's iris and ciliary body. Higher levels of serotonin can influence the pupil's muscles, leading to dilation. While this often causes a generalized mydriasis, case reports have documented unilateral effects leading to anisocoria.

Anticholinergic effects (TCAs)

Tricyclic antidepressants (TCAs) have anticholinergic properties, meaning they inhibit the action of acetylcholine, a neurotransmitter that helps constrict the pupil. By blocking these receptors, TCAs can paralyze the pupil sphincter muscle, resulting in pupil dilation. This effect is often more pronounced and a well-known side effect of TCAs, which may contribute to uneven pupil sizes.

Antidepressants Linked to Anisocoria

Though anisocoria is a rare adverse effect, several types of antidepressants, particularly SSRIs and TCAs, have been implicated in case reports.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Sertraline (Zoloft): Case reports have documented anisocoria associated with sertraline use, with one patient showing uneven dilation that resolved after discontinuing the medication.
Citalopram (Celexa): A case report detailed a patient with acute anisocoria related to citalopram, which resolved after the drug was stopped.
Escitalopram (Lexapro): Similar case reports show a link between escitalopram and anisocoria, an effect potentially related to anticholinergic features.
Paroxetine (Paxil): Anecdotal evidence and case reports have linked paroxetine to uneven pupillary dilation.
Fluoxetine (Prozac): Some studies mention fluoxetine in connection with pupil dilation.

Tricyclic Antidepressants (TCAs)

Amitriptyline (Elavil) & Nortriptyline (Pamelor): These older antidepressants are known to have significant anticholinergic effects that can cause mydriasis.

Other Antidepressants

Bupropion (Wellbutrin): Cited in literature for mydriasis and anisocoria.
Venlafaxine (Effexor): An SNRI that can cause pupil dilation due to its effect on serotonin and norepinephrine, similar to SSRIs.

Comparison of Antidepressant Effects on Pupils


Antidepressant Class	Primary Mechanism Affecting Pupils	General Effect on Pupils	Potential for Anisocoria
SSRIs (e.g., Sertraline, Citalopram)	Increased serotonin relaxes the iris sphincter muscle.	Mydriasis (dilation) is a known side effect.	Possible, due to varying sensitivity between the eyes.
TCAs (e.g., Amitriptyline, Nortriptyline)	Strong anticholinergic action blocks acetylcholine, paralyzing the iris sphincter.	Marked mydriasis (dilation) is common.	Possible, via anticholinergic effects.
SNRIs (e.g., Venlafaxine)	Increases serotonin and norepinephrine, affecting autonomic balance.	Mydriasis (dilation).	Possible, mechanism similar to SSRIs.

What to Do If You Experience Anisocoria

Sudden-onset anisocoria, especially when accompanied by other symptoms, is a medical emergency that requires prompt evaluation by a healthcare professional. While it could be a benign side effect of a medication, it can also signal a life-threatening neurological condition, such as a brain aneurysm, intracranial pressure, or head trauma.

Seek immediate medical attention if anisocoria occurs with:

Headache or neck pain
Droopy eyelid (ptosis)
Eye pain
Blurred or double vision

If the anisocoria is confirmed to be medication-induced and not a sign of a more serious issue, your doctor may decide to adjust your dosage or switch to a different antidepressant. In reported cases, the pupil size often returns to normal after discontinuing the offending medication. It is crucial not to make any changes to your medication regimen without consulting your prescribing physician.

Conclusion

While anisocoria is a rare ocular side effect of antidepressant use, it has been documented with several types of medications, particularly SSRIs and TCAs, primarily due to their effects on neurotransmitters that control pupil size. The phenomenon can result from an unequal response to the drug between the two eyes. While often benign, sudden-onset anisocoria, particularly with associated symptoms, warrants immediate medical evaluation to rule out serious underlying neurological conditions. Patients should always discuss any visual changes with their healthcare provider to determine the cause and the appropriate course of action.

For more detailed clinical information on the pharmacological effects of antidepressants on the eye, refer to resources like the National Center for Biotechnology Information.

Frequently Asked Questions

Pharmacologic anisocoria is a form of unequal pupil size that is caused by a medication or drug. In the context of antidepressants, this happens when the drug's effects on neurotransmitters like serotonin or acetylcholine lead to pupil dilation, which can affect one eye more than the other.

No, anisocoria is considered a rare side effect of antidepressants. While pupil dilation (mydriasis) is a more common ocular side effect, unequal pupil size is less frequently reported.

You should contact a healthcare provider or eye doctor immediately for a medical evaluation. While it may be a benign drug side effect, anisocoria can also be a symptom of a serious underlying medical condition, so it's important to be seen by a professional.

In most documented case studies, the anisocoria resolved after the implicated antidepressant was discontinued or the dosage was adjusted by a physician. Never change your medication regimen without professional medical guidance.

Yes. Tricyclic antidepressants (TCAs) are commonly associated with mydriasis due to their anticholinergic properties. Selective serotonin reuptake inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) can also cause pupil dilation through their effects on serotonin and norepinephrine.

Other potential side effects include blurred vision, dry eyes, and light sensitivity. In rare instances, there is an increased risk of acute angle-closure glaucoma in predisposed individuals with narrow drainage angles.

Yes. For example, if you touch an anticholinergic medication and then inadvertently rub your eye, it can cause the pupil in that eye to dilate, resulting in unilateral mydriasis and therefore anisocoria.

Doctors will conduct a thorough medical history, a neurological exam, and an eye examination. The presence of additional symptoms like headache, droopy eyelid, or vision changes would raise concern for a serious condition, prompting further tests to rule out neurological problems.