Chlorpromazine-Induced Skin Pigmentation With Short-Term Use in a Patient With Bipolar Disorder: A Case Report

Sir: Chlorpromazine is known, in rare instances, to induce skin pigmentation in areas exposed to sunlight.¹ The prevalence in chronic, hospitalized patients is reported as 1.0% to 2.9%.² Some authors report chlorpromazine-induced skin pigmentation as irreversible,³ while some findings⁴ indicate that it is completely reversible and that a variety of neuroleptics, including other phenothiazines, are used to replace chlorpromazine without risk of reemergence of pigmentation.⁴ Some authors³ suggest that chronic therapy with 500 mg/day or more of chlorpromazine is necessary to cause pigmentation, while others^5,6 report pigmentation at much lower doses. To our knowledge, there has been no report of skin changes in bipolar patients with short-term use of chlorpromazine.

Case report. Mr. A, a 30-year-old man diagnosed with bipolar affective disorder, current episode of mania with psychotic symptoms (per ICD-10 criteria), was treated with lithium carbonate tablets (1200 mg/day), chlorpromazine tablets (600 mg/day), and trihexyphenidyl tablets (2 mg/day). At the time of drug institution, there was no evidence of skin pigmentation or history of dermatologic problems. There was no history of prior exposure to chlorpromazine or of medical illnesses, and biochemical investigations revealed no abnormalities. He was still mildly euphoric and had difficulties initiating sleep, for which chlorpromazine was continued at the same dosage.

Three months later, in March 2004, he developed areas of diffuse hyperpigmentation over the sun-exposed parts of his face, neck, and shoulders compared to the rest of his body (Figure 1). There was no history of concomitant use of any other drugs except lithium and trihexyphenidyl. A possibility of chlorpromazine-induced skin hyperpigmentation was suspected. A slit-lamp examination of the eyes at this point revealed no corneal or lenticular deposits. Olanzapine tablets were started at 5 mg/day and raised to 20 mg/day, replacing chlorpromazine. There was only a slight decrease in pigmentation during follow-up in the next 2.5 years (Figure 2). A follow-up slit-lamp eye examination after 2.5 years revealed no corneal or lenticular deposits.

Figure 1.

Photograph of Patient in March 2004 Showing Hyperpigmentation Over Face, Neck, and Sun-Exposed Area of Chest

Figure 2.

Same Patient 2.5 Years Later

Our finding is different from past reports of skin changes following chronic exposure to chlorpromazine.^1,3 In contrast, our patient developed hyperpigmentation during short-term chlorpromazine exposure. Most of the cases described in the literature were chronically hospitalized patients diagnosed with schizophrenia,¹ whereas our patient was suffering from bipolar affective disorder. Previous reports show resolution of the skin changes occurring slowly over a period of 6 months to 5 years following substitution of chlorpromazine with other phenothiazines,⁴ loxapine,⁶ flupenthixol,⁷ and the atypical antipsychotic clozapine.⁸ The hyperpigmentation has remained unresolved in our patient in spite of replacing chlorpromazine with olanzapine, highlighting the need for a longer period of observation without chlorpromazine.⁴

This case underlines the need for clinicians and primary health care providers to be aware that chlorpromazine-induced skin pigmentation is a well-known side effect of this drug, regardless of the disease for which it is used, and that the time needed for developing the pigmentation seems to vary widely among patients.