Valproic acid-induced hyperammonemia: Incidence, clinical significance, and treatment management

Introduction: Valproic acid (VPA)-induced hyperammonemia poses several clinical challenges in psychiatric medicine. The reported incidence of this adverse effect varies widely across the literature. Furthermore, practitioners treat hyperammonemia in asymptomatic patients although studies suggest this practice is unnecessary. The purpose of this study is to evaluate if patients with VPA-induced hyperammonemia are appropriately identified for treatment based on their symptom presentation as well as determine the most efficacious treatment approach for VPA-induced hyperammonemia.

Methods: This study was completed at a community teaching hospital, and patients were retrospectively identified from June 1, 2011, to June 30, 2016, and included if they were admitted to a psychiatric unit, received at least 1 dose of VPA, and had at least 1 ammonia level drawn during admission. Hyperammonemia was defined as greater than 47 μmol/L, and symptomatic hyperammonemia was defined based on specific symptom presentation. The treatment modality was successful if the ammonia level was within normal range at discharge.

Results: Of the 357 patients screened, 347 patients met all inclusion criteria for analysis. The reported incidence of hyperammonemia was found to be 36% with 43.2% of those patients presenting with symptoms. Lactulose initiation was the most common treatment modality chosen (48.7%). Discontinuation of VPA was the most effective treatment (56.3% success rate).

Discussion: The results demonstrate that many patients with elevated ammonia levels are asymptomatic and therefore, based on findings within the literature, may not require treatment. Although lactulose was found to be the most common treatment initiated, the most effective was discontinuation of VPA.