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  • Title: Valproate oral loading in the treatment of acute mania.
    Author: Keck PE, McElroy SL, Tugrul KC, Bennett JA.
    Journal: J Clin Psychiatry; 1993 Aug; 54(8):305-8. PubMed ID: 8253698.
    Abstract:
    BACKGROUND: Evidence from earlier studies suggests that the antimanic activity of valproate becomes most pronounced within 1 to 4 days of achieving serum concentrations of 50 mg/L or greater. We conducted a prospective study to assess the onset of antimanic activity of oral loading dosages of valproate administered to achieve serum concentrations above 50 mg/L within 24 hours. METHOD: Nineteen patients with bipolar disorder, manic phase, received divalproex sodium 20 mg/kg/day in divided dosages for 5 days, without other psychotropic agents except lorazepam up to 4 mg/day. Serum valproate concentrations were measured after 1 and 4 days of treatment. Improvement was measured daily by a blind rater using the Young Mania Rating Scale (MRS). RESULTS: Serum valproate concentrations greater than 50 mg/L were reached in all 15 patients completing the study. Ten (53%) of the 19 patients who received at least one complete loading dose displayed a significant (greater than 50%) reduction in MRS scores by study termination. These responders displayed the greatest percent change in MRS scores over the first 3 days of treatment. Side effects were minimal. CONCLUSION: Valproate can be safely administered by oral loading and may produce rapid onset of antimanic response in some patients.
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