Valproate-associated hyperammonemic encephalopathy

The use of valproic acid (VPA) (also known as Depakote, Depakene, and others) frequently results in elevated plasma ammonia. In some people, hyperammonemia may be clinically significant, resulting in hyperammonemic encephalopathy, which may be severe. Valproic acid-induced hyperammonemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels of VPA. We describe 2 cases of valproic acid-induced hyperammonemic encephalopathy in patients with supratherapeutic VPA levels, although the condition has been described in people with normal VPA levels. With the increasing indications and off-label uses of VPA, family physicians should be aware of this potential complication of VPA and check ammonia levels in patients taking VPA who present with alterations in mental status. Treatment with L-carnitine may be beneficial in reducing ammonia levels.