Valproate-induced hyperammonemia: A case report

Valproate is a commonly prescribed drug for conditions such as epilepsy, bipolar affective disorder (BAD), and prophylaxis for migraine. It may infrequently lead to elevated serum ammonia levels, even when liver function is intact. Most cases are asymptomatic or present with non-specific neuropsychiatric symptoms, often leading to underdiagnosis. Symptoms range from mild cognitive disturbances to severe neurological impairment and may be life-threatening. It can often be misdiagnosed as a worsening psychiatric condition. In this case report, we present a case of a 58-year-old male diagnosed with BAD. The patient exhibited acute symptoms shortly after reinitiating valproate therapy despite years of stable valproate use. The diagnosis of hyperammonemia-induced delirium was confirmed on investigations. Valproate discontinuation coupled with supportive therapy in the form of lactulose and L-carnitine supplementation led to rapid clinical improvement. Rechallenge with valproate at lower doses, with close monitoring, was successful in this case. The case highlights the importance of early recognition of valproate-induced hyperammonemia (VIH) and prompt intervention, including valproate discontinuation, which allowed rapid symptom resolution.