VALPROATE ORAL LOADING IN THE TREATMENT OF ACUTE MANIA

Background. Evidence from earlier studies suggests that the antimanic activity of valproate becomes most pronounced within 1 to 4 days of ac hieving serum concentrations of 50 mg/L or greater. We conducted a pro spective study to assess the onset of antimanic activity of oral loadi ng dosages of valproate administered to achieve serum concentrations a bove 50 mg/L within 24 hours. Method. Nineteen patients with bipolar d isorder, manic phase, received divalproex sodium 20 mg/kg/day in divid ed dosages for 5 days, without other psychotropic agents except loraze pam 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 valproa te concentrations greater than 50 mg/L were reached in all 15 patients completing the study. Ten (53%) of the 19 patients who received at le ast one complete loading dose displayed a significant (greater than 50 %) reduction in MRS scores by study termination. These responders disp layed 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 ant imanic response in some patients.