Understanding Olanzapine's Mechanism of Action
Olanzapine is a second-generation (atypical) antipsychotic medication used to treat conditions like schizophrenia and bipolar disorder [1.8.1]. Its therapeutic effects are believed to stem from its ability to block dopamine (D2) and serotonin (5HT2A) receptors in the brain [1.8.1, 1.8.2]. However, olanzapine is not perfectly selective and interacts with a wide range of other receptors, including muscarinic, histamine, and adrenergic receptors [1.8.2]. This broad receptor profile is responsible for both its therapeutic actions and its diverse side effects, including those affecting the eyes.
The Dual Effect on Pupil Size: Mydriasis vs. Miosis
The question of whether olanzapine causes pupil dilation (mydriasis) or constriction (miosis) has a nuanced answer because the drug has two opposing mechanisms of action.
The Case for Pupil Dilation (Mydriasis)
Olanzapine has a moderate affinity for muscarinic M1-5 receptors, acting as an antagonist [1.8.2]. This gives it anticholinergic properties. Anticholinergic drugs block the action of acetylcholine, a neurotransmitter that, among many functions, causes the pupillary sphincter muscle to contract, making the pupil smaller [1.6.4, 1.6.5]. By blocking these receptors, olanzapine can lead to pupil dilation [1.3.1].
This dilation is considered a rare side effect, reported in 0.01% to 0.1% of users of oral olanzapine [1.10.1, 1.11.2]. However, this effect can be clinically significant. The pupil dilation caused by olanzapine's anticholinergic activity can increase the risk of an acute angle-closure glaucoma (AACG) attack in individuals with predisposing anatomical factors, such as narrow angles [1.5.2, 1.7.1, 1.7.3]. AACG is a medical emergency characterized by a sudden increase in intraocular pressure that can lead to vision loss if not treated promptly [1.7.4].
The Case for Pupil Constriction (Miosis)
Paradoxically, olanzapine is more frequently associated with pupil constriction (miosis or "pinpoint pupils"), particularly in cases of overdose [1.2.1, 1.4.3]. This effect is primarily due to olanzapine's antagonism of alpha-1 adrenergic receptors [1.2.2, 1.8.2]. The alpha-1 receptors are found on the iris dilator muscle; stimulating them causes the pupil to widen. By blocking these receptors, olanzapine allows the parasympathetic system (which constricts the pupil) to dominate, resulting in miosis [1.6.3].
Several case reports and studies have documented miosis as a key sign of olanzapine toxicity [1.2.1, 1.4.1, 1.4.2]. In fact, olanzapine overdose can sometimes mimic opioid intoxication due to the presentation of central nervous system depression and pinpoint pupils [1.4.3]. One study of olanzapine intoxications found that miosis was present in 31% of cases [1.4.1].
Comparison with Other Antipsychotics
The ocular side effects of antipsychotics can vary significantly between different medications. A comparison helps to contextualize olanzapine's effects.
| Feature/Effect | Olanzapine | Aripiprazole (Abilify) | Quetiapine (Seroquel) | Chlorpromazine (Thorazine) |
|---|---|---|---|---|
| Primary Pupil Effect | Miosis (esp. in overdose) [1.2.2, 1.4.4] | Can cause both dilation and constriction [1.2.3, 1.9.2] | Miosis [1.2.2, 1.4.4] | Miosis [1.4.4] |
| Mechanism for Miosis | Alpha-1 adrenergic blockade [1.2.2] | Alpha-1 adrenergic blockade [1.6.3] | Alpha-1 adrenergic blockade [1.2.2] | Alpha-1 adrenergic blockade |
| Mechanism for Mydriasis | Weak anticholinergic effects [1.7.4, 1.8.2] | Dopamine/serotonin effects [1.9.1] | Weaker anticholinergic effects | Strong anticholinergic effects |
| Glaucoma Risk | Risk of acute angle-closure [1.7.2, 1.7.3] | Less established risk | Mentioned as a potential risk | Risk of acute angle-closure |
| Other Ocular Effects | Blurred vision, dry eyes, rare oculogyric crisis [1.5.1, 1.9.3] | Blepharospasm, blurred vision [1.9.3] | Cataracts (in long-term animal studies) | Corneal and lens deposits [1.5.4] |
Other Ocular Side Effects of Olanzapine
Besides changes in pupil size, olanzapine is associated with other ocular side effects. Patients should be aware of these potential issues and report them to their healthcare provider.
- Common (1% to 10%): Blurred vision and amblyopia (lazy eye) are among the more frequently reported ocular side effects [1.5.1, 1.11.2].
- Uncommon (0.1% to 1%): Dry eyes, abnormalities in visual accommodation (focusing), and oculogyration (circular movement of the eyeballs) can occur [1.5.1, 1.11.2].
- Rare/Frequency Not Reported: Oculogyric crisis (OGC), a rare but distressing dystonic reaction where the eyes are involuntarily deviated (usually upwards), has been linked to olanzapine [1.5.3, 1.11.4].
Conclusion
So, does olanzapine cause dilated pupils? The answer is yes, but rarely. Its weak anticholinergic properties can induce mydriasis, which poses a significant risk for individuals predisposed to acute angle-closure glaucoma [1.5.5, 1.7.1]. However, pupil constriction (miosis) is a more characteristic finding, especially in the context of olanzapine overdose, due to the drug's potent blockade of alpha-1 adrenergic receptors [1.4.1, 1.4.4]. In therapeutic doses, one study noted that olanzapine had minimal effect on the pupillary light reflex compared to aripiprazole [1.9.1]. Ultimately, the effect on a patient's pupils can be variable. Any changes in vision, eye pain, or noticeable difference in pupil size should be discussed immediately with a healthcare professional.
For more information on olanzapine, you can review the FDA-approved information on MedlinePlus. [1.11.3]
