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EV1120

Possible thioridazine-associated asymmetric iris hyperpigmentation in an adult with intellectual disability: a case of an underrecognized psychopharmacological adverse effect

POSSIBLE THIORIDAZINE-ASSOCIATED ASYMMETRIC IRIS HYPERPIGMENTATION IN AN ADULT WITH INTELLECTUAL DISABILITY: AN UNDER-RECOGNIZED PSYCHOPHARMACOLOGIC ADVERSE-EFFECT CASE

In patients with limited ability to report symptoms, detecting rare adverse effects depends on proactive examination; melanin-binding phenothiazines may be associated with pigmentation even years after discontinuation.

The aim is to evaluate past thioridazine exposure as an explanation for asymmetric iris hyperpigmentation after common secondary causes have been excluded. The case concerns a 50-year-old woman with lifelong intellectual disability and epilepsy who had taken thioridazine at doses of up to 600 mg/day for 14 years and discontinued it approximately 8 years earlier; concomitant psychotropic medications were carbamazepine 800 mg/day and quetiapine 300 mg/day. During routine follow-up, the clinician incidentally observed bilateral iris hyperpigmentation, more pronounced on the right. Collateral information from those close to the patient indicated no visual complaints. An ophthalmology consultation was requested, secondary causes were systematically excluded, and no specific ophthalmic etiology was identified. The literature indicates that phenothiazines bind to melanin with high affinity and accumulate in uveal tissue, that pigmentary retinopathy is the best-documented form of thioridazine-related ocular toxicity, and that ocular pigmentation was observed in 73 of 100 long-term users. In the causality assessment, the high cumulative dose, absence of a more compelling alternative etiology, and melanin affinity consistent with delayed ocular toxicity supported a possible association with thioridazine. The 8-year interval remained within the reported window of tissue persistence (retinal changes have been reported 13 to 28 years after discontinuation), but because iris-specific support was indirect and based solely on analogy with chlorpromazine and imipramine, causality was not rated higher than “possible” under the WHO-UMC (World Health Organization–Uppsala Monitoring Centre) system. The dark green iris color and limited sun exposure due to a largely indoor lifestyle made a phototoxic contribution less likely. The authors note that, in the absence of self-report, detection depends on proactive examination and timely specialist referral, that follow-up of adults with intellectual disability receiving long-term psychotropic treatment should remain multidimensional, and that reports with limited evidence of causality also contribute to pharmacovigilance signals. Written consent for publication was obtained from the patient's legal representative.

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