Mood changes are a rare side effect of methotrexate therapy, but ask about psychiatric side effects when using the drug, as when treating dermatologic disease, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.

Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.

A 16-year-old girl with generalized lichen sclerosus and no prior psychiatric history began weekly oral methotrexate 10 mg (0.18 mg/kg) with folic acid supplementation 6 days per week after failing topical treatment and narrow-band ultraviolet B therapy. After her first two doses, she and her mother noted that she was feeling negative, had depressed mood, and was “mouthing off” to her parents. After 13 days, methotrexate was stopped, and her psychiatric symptoms went away within 2 weeks.

An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.

It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.

Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406 ).


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