Valproic Acid—Induced Hyperammonemia in a Patient With Schizoaffective Disorder

Abstract

Valproic acid is used in psychiatry as a mood stabilizer and can be very effective in reducing symptoms of agitation. Valproic acid may cause hyperammonemia through carnitine deficiency created by its inhibition of mitochondrial enzymes in the urea cycle. Clinical presentation of hyperammonemia usually involves lethargy and somnolence, which may also be noted with therapeutic serum concentration during valproic acid therapy. The diagnosis of hyperammonemia is often overlooked due to a clinical presentation that may include normal liver enzyme tests and serum valproate levels that are within the therapeutic range. Treatment modalities may include discontinuation of valproic acid therapy, lactulose, naloxone, and hemodialysis. Carnitine supplementation, for both prevention and acute treatment of hyperammonemia, has been anecdotally reported and may be considered. This article illustrates a case of an adult male with schizoaffective disorder who was treated with valproic acid and subsequently developed hyperammonemia, despite therapeutic valproic acid serum levels and normal liver enzyme tests. Possible causes of hyperammonemia and current treatment options will be described, as well as suggestions for monitoring for this adverse event in the clinical setting.

Keywords

valproic acid hyperammonemia schizoaffective disorder urea cycle lactulose naloxone carnitine.

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