ORAL LOADING DOSES IN THE VALPROATE TREATMENT OF ADOLESCENTS WITH MIXED BIPOLAR DISORDER

Five adolescent patients (ages 13-17) with DSM-III-R bipolar disorder, mixed type, were hospitalized for acute mania and prospectively treated with open-label valproate administered as an initial oral loading dose of 20 mg/kg. Initial nightly valproate doses ranged from 750 to 1500 mg, and serum valproate concentrations the following morning ranged from 46 to 84 mg/L, (mean 64). Patients were closely monitored for 4-12 days (mean 8) until discharged. Two patients also received concurrent psychotropic medications. Adverse effects were minimal, consisting mainly of transient mild to moderate sedation. Three of 5 patients appeared to improve substantially, one patient displayed some improvement, and one patient demonstrated no response to valproate as measured by changes in the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Global assessment Scale. These data suggest that valproate may be well tolerated when administered with an initial loading dose and that valproate may be effective in some severely ill adolescents with bipolar disorder. However, these preliminary findings should be interpreted with caution as controlled studies are needed to examine the efficacy and safety of valproate, including when administered with a loading dose in adolescents with bipolar disorder.