Severe fatigue due to valproate-induced hypothyroidism in a case of bipolar disorder
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Annals of General Psychiatry Open Access
CASE REPORT
Severe fatigue due to valproate‑induced hypothyroidism in a case of bipolar disorder Tadashi Kanamori1,2, Masahiro Suzuki1*, Yoshiyuki Kaneko1, Kouju Yamada1,2, Hideyuki Kubo1 and Makoto Uchiyama1,3
Abstract Background: Valproate-induced hypothyroidism is a rare condition and has been considered asymptomatic. Here, we report a case of bipolar I disorder who developed symptomatic valproate-induced hypothyroidism. Case presentation: A 44-year-old woman with bipolar I disorder complained of severe fatigue after starting valproate. She showed a hormonal pattern of central hypothyroidism. Thyroid autoantibodies were negative, and no pituitary abnormality was seen on magnetic resonance imaging. After stopping valproate, her severe fatigue rapidly improved with normalizing thyroid function. Conclusions: Our case suggests that valproate-induced hypothyroidism should be considered when patients complain of excessive fatigue under treatment with valproate. Keywords: Bipolar disorder, Hypothyroidism, Symptomatic, Valproate Background Valproate, which is recognized to be much safer than lithium, the archetypal mood stabilizer, in terms of effects on thyroid function, is widely used in the treatment of bipolar disorder [1]. However, previous reports have suggested that valproate can also cause hypothyroidism [2, 3]. Here, we report a case of bipolar disorder showing severe fatigue due to valproate-induced hypothyroidism. Case presentation A 44-year-old woman with bipolar disorder was referred to our outpatient clinic 2 months after her first manic episode. She developed bipolar disorder with depressive episodes when she was 42 years old. Her first depressive episode was ameliorated with 3 months’ treatment with sertraline. She had no previous episodes of hypomania or mixed states, and no history of thyroid disease. When she
*Correspondence: suzuki.masahiro94@nihon‑u.ac.jp 1 Department of Psychiatry, Nihon University School of Medicine, 30‑1 Oyaguchi‑Kamicho, Itabashi‑ku, Tokyo 173‑8610, Japan Full list of author information is available at the end of the article
presented at our clinic, she had been treated with quetiapine for 1 month, but still had elevated mood, irritability, and mood-congruent delusions. According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, we diagnosed her as having bipolar I disorder, and added 200 mg of valproate on 100 mg of quetiapine. Valproate was later increased to 400 mg, after which, her manic symptoms ameliorated. Despite her mood being well controlled, she developed severe fatigue 30 days after starting valproate. She had no depression-related symptoms other than fatigue, and no findings suggesting sedation with valproate such as somnolence or impaired attention. Her blood concentration of valproate was 24.2 μg/mL, which was not at the toxic level (normal range 50–100 μg/mL). She had never had a similar reaction to previously used psychotropics. A physical examination and laboratory test found no abnorm
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