A RANDOMIZED COMPARISON OF DIVALPROEX ORAL LOADING VERSUS HALOPERIDOLIN THE INITIAL TREATMENT OF ACUTE PSYCHOTIC MANIA

Background: Uncontrolled evidence suggests that divalproex administere d via the oral loading strategy of 20 mg/kg/day may produce clinically significant antimanic response within 3 days of treatment in some pat ients. We conducted a prospective study to compare the antimanic respo nse of divalproex oral loading with that of haloperidol in the initial treatment of acute psychotic mania. Method: After a less than or equa l to 1-day screening period, 36 consecutive hospitalized patients with bipolar disorder, manic or mixed phase and with psychotic features, w ere randomly assigned to receive either divalproex 20 mg/kg/day or hal operidol 0.2 mg/kg/day for 6 full days, without other psychotropic age nts except lorazepam up to 4 mg/day for management of agitation. Serum valproate concentrations were measured after 1 day of treatment. Resp onse was measured daily by a blind rater using the Young Mania Rating Scale and the Scale for Assessment of Positive Symptoms. Results: Diva lproex oral loading and haloperidol were equally effective in acutely reducing manic and psychotic symptoms. The greatest rate of improvemen t for both drug regimens occurred over the first 3 full days of treatm ent. Side effects were infrequent and minor for both treatments, excep t for extrapyramidal side effects, which were significantly more commo n with haloperidol. Conclusion: Divalproex oral loading may produce ra pid onset of antimanic and antipsychotic response comparable to that o f haloperidol and with minimal side effects in the initial treatment o f acute psychotic mania in a subset of bipolar patients.