Evidence from earlier studies indicates that the antimanic action of valproate becomes most apparent within 1-4 days of achieving serum concentrations 50 µg/ml, that valproate can be orally loaded with achievement of therapeutic serum concentrations within the first several days of treatment, there is a rapid onset of response, and minimal side effects. To provide further data on the safety and efficacy of valproate oral loading in the treatment of acute mania, we evaluated 13 consecutive patients with acute manic syndromes who received valproate initiated at a dosage of 20 mg/kg/day. In most cases, valproate was added to other psychotropics. All 13 patients received at least 5 full days of valproate maintained at or above 20 mg/kg/day, and valproate serum concentrations were 50 µg/ml (mean ± SD = 88 + 25) by the second or third day of treatment. Ten (77%) patients displayed a moderate or marked response. Side effects were infrequent and minor. Consistent with our earlier study, these findings suggest that valproate can be safely administered via a loading dose of 20 mg/kg/day to patients with acute mania, including those on other psychotropics, and that it may produce a rapid response with minimal side effects.

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