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Mirtazapine and hyperpigmentation

Sir, Among the antidepressants, mirtazapine has a unique structure and mechanism of action, which could be best described as a nonadrenergic and specific serotonergic antidepressant. Common side effects of this drug are somnolence, dry mouth, increased appetite and weight gain (Montgomery 1995). We report a case of a woman with depressive disorder who was being treated with mirtazapine and developed hyperpigmentation in photo-sensitive areas. To our knowledge, this is the first reported side-effect in the existing literature. Mrs A, a 38-year-old fair-complexioned married woman presented to us with a history of sadness, anxiety, disturbed biological functioning and low confidence levels of 2 years duration. Her symptoms met DSM-IV criteria for major depressive disorder. In the initial phase of her illness, for approximately 18 months, she was drug nave and had undergone a few sessions of psychotherapy without any improvement. Subsequently, she was started on imipramine 25 mg/day but this medication was discontinued after 15 days because of severe dryness of mouth and constipation. She was then started on mirtazapine 7.5 mg/day which was increased to 15 mg/day over a period of 2 weeks. She tolerated this drug very well and showed good clinical response with improvement in sadness of mood and biological functioning. She, however, had a recurrence of depressive symptoms when the dose of mirtazapine was reduced to 7.5 mg. She was therefore stabilized on a daily dose of 15 mg of mirtazapine. After 8 months of mirtazapine therapy, she and her family members noticed a darkening of her skin complexion in the exposed areas of her body such as face, extensor part of forearm and posterior aspect of the neck. However abnormal pigmentation was absent in the sclera, nails and teeth. There was no history of any dermatological disorder preceding the administration of mirtazapine therapy. She did not have any endocrinological abnormalities and all her routine investigations were within normal limits including serum iron and blood glucose levels. Mrs A denied having used new soap, cream or different kind of food. She also denied more exposure to sunlight than usual and was not pregnant. Dermatological consultation confirmed it as a case of hyperpigmentation. She refused to give consent for a skin biopsy stating cosmetic reasons. Mirtazapine was discontinued completely and it was replaced with sertraline 100 mg/day. She showed mild improvement in her hyperpigmentation over the next 6 months. The probability of an adverse drug reaction was assessed using the Naranjo probability scale (Naranjo et al. 1981).This indicated a possible association between mirtazapine and hyperpigmentation. A literature review and PubMed search found that, besides tricyclic antidepressant drugs (Metelitsa et al. 2005), there have been reports of hyperpigmentation with citalopram (Inalz et al. 2001) and sertraline (Ghanizadeh 2007). A similar search (using the keywords mirtazapine, pigmentation and hyperpigmentation) found no published reports of hyperpigmentation with mirtazapine. Our finding is important: firstly because atypical antidepressants