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Updated: Aug 11, 2025

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Published on: November 8, 2018
[A severe, reversible encephalopathy after prolonged use of valproic acid]
Abstract:
Valproic acid is an effective mood stabilizer, registered for the treatment of bipolar disorder and epilepsy. Side effects of valproic acid are transient and generally well tolerated. A rare side effect is a valproic acid-induced encephalopathy. We saw a case of valproic acid-induced encephalopathy without hyperammonemia in a 71-year-old woman. She had used valproic acid as a mood stabilizer over the course of 16 years for a bipolar I disorder. The following clinical symptoms were observed: staring eye contact, somnolence, disorientation, hypotenacity, bradyfrenia, mutism and akathisia. Severe extrapyramidal symptoms were observed during neurological examination as well as hyperreflexia, a snoutreflex on both sides and a right-sided palmomental reflex. After cessation of the valproic acid, her symptoms disappeared completely. Based on this case report, we discuss the clinical aspects, pathophysiology, recognition and treatment of valproic acid-induced encephalopathy, both with and without hyperammonemia.
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