Valproate
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Fatigue secondary to hypothyroidism: case report A 44-year-old woman developed fatigue secondary to hypothyroidism during treatment with valproate for bipolar I disorder. The woman was referred to a clinic in Japan 2 months after her first manic episode. She had developed bipolar disorder with depressive episodes at the age of 42 years. Her first depressive episode was successfully treated with sertraline. When she presented to clinic, she had been receiving quetiapine for 1 month, but had persistently elevated mood, irritability and moodcongruent delusions. She was diagnosed with bipolar I disorder. She started receiving valproate 200mg [route not stated] along with quetiapine. Later, the dose of valproate was increased to 400mg. Thereafter, her manic symptoms ameliorated. After 30 days from the initiation of valproate, she developed severe fatigue. Blood valproate concentration was 24.2 µg/mL (normal range 50–100 µg/mL). A physical examination and laboratory test showed no abnormalities except for low values of free thyroxine (FT4) and free triiodothyronine (FT3). Thyroid-stimulating hormone (TSH) levels were within normal range, suggesting central hypothyroidism. After ruling out other fatigue-causing medical conditions and medications by systematic evaluations, the severe fatigue was considered to be secondary to hypothyroidism. She tested negative for thyroid autoantibodies. Gadolinium-enhanced pituitary gland MRI showed no evidence of a pituitary lesion. Given the simultaneous decrease in her FT4 levels with increasing doses of valproate, her hypothyroidism was suspected to be due to valproate. The woman’s treatment with valproate was stopped 33 days following its initiation. Consequently, severe fatigue improved and completely disappeared in about 20 days. Thirty five days following the discontinuation of valproate her thyroid function had normalised. For the following 12 months, there was no recurrence of hypothyroidism, fatigue or mood episodes under maintenance treatment with carbamazepine and risperidone. Causality assessment using Naranjo Adverse Drug Reaction Probability Scale showed "Probable" relationship between hypothyroidism and valproate with score of 8. Kanamori T, et al. Severe fatigue due to valproate-induced hypothyroidism in a case of bipolar disorder. Annals of General Psychiatry 19: 2020. Available from: URL: http:// 803506625 doi.org/10.1186/s12991-020-00299-y
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Reactions 10 Oct 2020 No. 1825
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