Valproate-Induced Hyperammonemic Encephalopathy in General Hospital Patients With One or More Psychiatric Disorders

Abstract

Divalproex sodium/valproic acid (VPA) is an antiepileptic drug approved for use in epilepsy and bipolar disorder. Valproate-induced hyperammonemia occurs in up to 50% of VPA-treated patients, some of whom may become encephalopathic. Valproate-induced hyperammonemic encephalopathy (VHE) is thought to be rare, and for a variety of reasons, the diagnosis requires a high index of suspicion. The study's goals are to determine how common VHE is, and the quality of treatment provided when diagnosed. Retrospective, cross-sectional survey of general hospital patients. The hospital's laboratory and pharmacy databases were combined to identify a cohort of all VPA-treated patients who developed hyperammonemia during a 5-year period. Hospital records of the subset of patients with a psychiatric disorder were selected and reviewed for data collection. Twenty of 793 (2.52%) VPA-treated patients had signs and symptoms consistent with VHE. The majority were White males on multiple psychotropic agents. Valproate was appropriately discontinued in 8 (40%) patients. Lactulose was the only ammonia-lowering drug used, and it was administered to 6 patients and only one among them had VPA discontinued. Study results indicate that VHE may be more common in psychiatric patients than previously assumed but underrecognized and inadequately treated. The diagnosis of VHE requires a high index of suspicion. Outcome is favorable once it is recognized and treated appropriately.