Valproate-Related Hyperammonemia in Older Adult Psychiatric Inpatients

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To the Editor: Valproate is indicated for treatment of seizure disorders and mania in bipolar disorder and is prescribed off-label to treat impulsivity, aggression, irritability, and agitation in other disorders. Prescribing information for valproate includes warnings for hyperammonemic encephalopathy in individuals with urea cycle disorders and for hyperammonemia despite normal liver function tests. A cohort study of 123 valproate-treated psychiatric inpatients (mean age of 45.1 years) reported a valproate-related hyperammonemia rate of 51.2%.