When Treatment Leaves a Mark: Trifluoperazine-associated Hyperpigmentation in a Case Series

Abstract

Abstract Drug-induced skin hyperpigmentation is a known but often overlooked side effect of phenothiazine antipsychotics. While chlorpromazine is commonly implicated, reports involving trifluoperazine are limited. Because psychiatric treatment is often long term and involves multiple medications, such changes may go unnoticed or be attributed to other causes. We describe five patients receiving trifluoperazine for psychiatric illnesses who gradually developed skin hyperpigmentation. Clinical details, duration of exposure, associated medications, and changes after stopping treatment were reviewed. All patients developed pigmentation after 1–4 years of trifluoperazine use, mainly over sun-exposed areas of the face. In three patients with follow-up data, stopping trifluoperazine resulted in marked or complete improvement within 2–3 months. One patient showed no improvement after stopping divalproex sodium alone, but pigmentation faded after trifluoperazine withdrawal, supporting its likely role. Two patients were lost to follow-up. Trifluoperazine may be an under recognized cause of reversible skin hyperpigmentation. Awareness and early recognition can help reduce distress, improve adherence, and guide timely treatment modification.