Carnitine as an antidote for acute valproate toxicity in children

Valproic acid is a widely used anticonvulsant that has recently been approved for stabilization of manic episodes in patients with bipolar disorder. As the use of valproic acid increases, the number of both accidental and intentional exposures increases. This is paralleled by more reports of valproic-acid-induced toxicity. The purpose of this article is to review the pathophysiology and toxicology of valproic acid and determine whether the literature supports the use of carnitine as a treatment for acute valproic-acid-induced toxicity.

Recent literature documents no cases of allergic reactions or serious side effects associated with the administration of carnitine when given patients with acute ingestions of valproic acid. Other findings suggest that carnitine increases the survival rate of patients who develop valproic-acid-induced hepatotoxicity. Early intervention with intravenous rather than enteral L-carnitine was associated with the greatest hepatic survival. Isolated pediatric case reports show that carnitine administration may reverse toxic metabolic pathways but may not hasten clinical improvement.

Based on this recent literature, it seems reasonable to use carnitine for documented severe valproic acid toxicity, particularly in cases where patients present with coma, rising ammonia level, or valproic acid levels greater than 450 mg/l.