Valproic acid rechallenge after valproate-induced hyperammonemic encephalopathy

A 24-year-old man with a past medical history of behavioral disturbances and spastic tetraplegia secondary to traumatic brain injury presented to the psychiatry consult service with acute exacerbation of agitation and aggression. The patient's behavioral disturbances were previously reduced with 1500 mg daily of valproic acid (VPA). Prior to admission, VPA was discontinued due to elevated serum ammonia levels of 96 μmol/L and clinical findings consistent with valproate-induced hyperammonemic encephalopathy (VIHE), such as lethargy, confusion, frank delirium, and ataxia. Current guidelines for treating VIHE suggest either a complete discontinuation of the drug or a drug rechallenge with the addition of levocarnitine or carglumic acid supplementation. In this case, VPA was rechallenged without supplementation to decrease the risk of noncompliance. The patient received a lower dose of VPA with subsequent up-titration. His ammonia level decreased to an acceptable level. This case report discusses the challenges of managing VIHE in patients requiring VPA and discusses opportunities for further research in preventing VIHE.