Imipramine-Associated Hyperpigmentation

OBJECTIVE: To inform clinicians of the potential for severe and persistent facial hyperpigmentation with the long-term use of imipramine. CASE SUMMARY: A 65-year-old white male veteran with a history of paranoid schizophrenia was referred to the psychiatry service by a dentist who thought that the patient was both cyanotic and psychotic. The history and biopsy results indicated the possibility of imipramine-associated hyperpigmentation, only the second reported case in a male patient. The presentation was complex, with a history of neuroleptic exposure and multiple signs of parkinsonism. A brain single photon-emission computed tomography scan demonstrated frontal lobe hypermetabolism and bilateral caudate hypermetabolism, which normalized 14 months later. Despite discontinuation of imipramine, the patient continued to appear cyanotic, leading to worsening social isolation. He became known as “the man with the purple face.” On his rare ventures outside the home, he was embarrassed by sporadic calls to 911 by persons fearing he was ill. DISCUSSION: Although facial hyperpigmentation secondary to the use of phenothiazines has been reported frequently, it is much less common with imipramine, and is very rare in males. Failure to recognize this adverse reaction led to continuing treatment with imipramine and to an apparently irreversible condition. The brain imaging findings have no link with the hyperpigmenting process, but raise questions about neuroleptic-induced metabolic changes in the brain. CONCLUSIONS: Clinicians need to be aware of rare adverse reactions such as hyperpigmentation, and be prepared to take appropriate and early action to prevent such reactions from becoming irreversible.