The risk of hyperammonemic encephalopathy on epilepsy and psychiatric patients: insight from FAERS data and published case reports

Valproate-associated hyperammonemic encephalopathy (VHE) is a serious adverse event. However, its risk profiles and clinical features remain poorly characterized across different patient populations. This study aimed to compare the incidence, clinical presentation, and outcomes of VHE between patients with epilepsy and those with psychiatric disorders. ology: This study integrates pharmacovigilance data derived from the US FDA Adverse Event Reporting System (FAERS; January 2013-September 2024), with a systematic review of case reports from PubMed and Embase (up to Feb 2025). Emphasize the distinctions in demographic profiles, clinical indicators, and duration of recovery observed between the two cohorts. For 549 VHE cases in the FAERS database, 312 case involved epilepsy and 237 involved psychiatric. After adjusting for age and sex, psychiatric exhibited a significantly lower risk of VHE ([OR] = 0.60, 95%[CI]: 0.51-0.70). Analysis of 134 literature-derived cases revealed that elevated blood ammonia was more common in psychiatric (100% vs. 80.2%), although their serum valproate levels were lower (Median 142.0 vs. 237.3 μg/mL). Kaplan-Meier analysis indicated a shorter median recovery time in psychiatric (2 vs. 5 days). Cox regression further confirmed this result (HR=2.47), particularly in adults (HR = 2.55) and females (HR = 3.34). The type of indication significantly influences the risk and prognosis of VHE. Individuals with epilepsy exhibit greater sensitivity to VPA and experience a prolonged recovery period in comparison to psychiatric. Customized monitoring strategies informed by specific diagnoses are essential to enhance the safety profile of VPA.