Reactions 747 - 17 Apr 1999

Imipramine

Skin pigmentation: 4 case reportsFour women developed hyperpigmentation on sun-exposed

skin on their faces, necks, arms and hands during long-termtreatment with imipramine.

The first patient, aged 54 years, took imipramine 300mg/day for 15 years for depression. She noted worseninghyperpigmentation over the past 3–4 years, and darkening ofher irises. Treatment with tretinoin cream and hydroquinonecream was ineffective, but she refused to discontinueimipramine.

The second patient, aged 75 years, received imipramine150–200 mg/day for 10 years for depression. After 4 years’treatment, she also noticed darkening of her skin. Treatmentwith laser therapy and a ‘bleaching’ cream had no effect. Thewoman continued to take imipramine.

The third patient, aged 53 years, took imipramine 350–375mg/day for 14 years for panic disorder. After 10 years’ therapy,she developed darkening of her skin. Hydroquinone solutionwas administered, with no improvement. Imipramine wasdiscontinued and fluoxetine started and the patient’shyperpigmentation resolved over the next 6 months.However, the hyperpigmentation recurred 1 month afterfluoxetine was replaced with desipramine.

The fourth patient, aged 66 years, started to develophyperpigmentation of her skin 2 years after she startedimipramine 350 mg/day for depression. Two years later,imipramine was replaced with amitriptyline and herhyperpigmentation resolved almost completely over the nextyear.

Skin biopsies from the 4 patients showed golden-browngranules of various sizes in the superficial and mid dermis.Fontana-Masson staining was strongly positive. Electronmicroscopy showed the granules to be located in membrane-bound lysosomal structures of dermal perivascular andperineural macrophages. Further investigations showed thegranules contained sulphur-containing material.

Author comment: ‘We hypothesize that the granules ofimipramine-induced hyperpigmentation containphaeomelanin, a sulfur-containing compound, or a relatedmetabolite. Normal melanogenesis may be disrupted byimipramine through an unknown mechanism, leading toabnormal melanin deposition.’Ming ME, et al. Imipramine-induced hyperpigmentation: four cases and a reviewof the literature. Journal of the American Academy of Dermatology 40: 159-166,Part 1, Feb 1999 - USA 800745957

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Reactions 17 Apr 1999 No. 7470114-9954/10/0747-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved