Valproic Acid–Associated Hyperammonemia

Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA-induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management.