Levocarnitine for valproate-induced hyperammonemia in the psychiatric setting: A case series and literature review

INTRODUCTION: Hyperammonemia is a potential adverse effect of valproic acid (VPA) therapy, which is often asymptomatic but can lead to severe, life-threatening encephalopathy. Carnitine deficiency due to VPA is the proposed mechanism for hyperammonemia and the development of VPA-induced hyperammonemic encephalopathy (VHE). Levocarnitine, the active form of carnitine, has been suggested for treatment and prevention of VHE. METHODS: Data was collected by chart review of 3 patients who received oral levocarnitine supplementation in the psychiatric setting for VPA-induced hyperammonemia. Review of the literature was performed through June 2017 using the following PubMed search terms: valproate, valproic acid, hyperammonemia, altered mental status, encephalopathy, and levocarnitine. Articles were included if they described use of levocarnitine in VPA-treated patients with psychiatric disorders. RESULTS: One patient developed encephalopathy with resolution of symptoms after VPA discontinuation. Valproic acid was restarted with the addition of levocarnitine to prevent VHE reoccurrence. In the other 2 cases, levocarnitine was started prophylactically in patients who developed hyperammonemia without emergence of any clinical symptoms. Ammonia levels were reduced to normal in all cases, and no symptoms consistent with encephalopathy were reported. The literature search identified 6 additional cases with 5 of 6 reports supporting use of levocarnitine for decreased ammonia levels as well as an observational trial. DISCUSSION: This literature review and case series illustrates successful use of levocarnitine supplementation for reduction of ammonia levels in the setting of VPA-induced hyperammonemia among patients with psychiatric disorders. However, clinical significance of ammonia reduction in asymptomatic patients is difficult to determine.