Bipolar disorder (BPD) in children and adolescents is increasingly recognized as a common and virulent disorder, but evidence-based treatment approaches are lacking. This revised, proposed study develops evidence to address this significant knowledge gap, and helps to develop more empirically based treatments of child and adolescent BPD. This three-site, collaborative treatment study proposes to evaluate the acute phase, comparative efficacy of two mood stabilizers, lithium (LI) and divalproex sodium (DVP) versus placebo (PBO) in outpatient children and adolescents with symptomatic, nonpsychotic BPD I in the mixed or manic phase. Investigators at 3 sites (UTSW, Case Western Reserve & Univ. of Cinn.) will randomize 150 patients over 3 years. To our knowledge, this represents the first randomized, controlled the comparing the efficacy of each mood stabilizer versus placebo in this population. This will be accomplished by randomly assigning subjects in a double-blinded fashion to 8 weeks of treatment with either LI, DVP, or PBO. The primary aim of this project is to compare the efficacy of LI, DVP, and PBO in the acute phase treatment of symptomatic bipolar I disorder, in children and adolescents ages 8-17 yr. Our hypothesis is that differential efficacy will be observed with the following predicted order of response: DVP equals LI > PBO. The secondary aims are: 1)To provide descriptive data and effect size estimates of combined treatment with LI and DVP in patients who do not respond acutely to either one alone; 2) To collect systematic safety data on the incidence of weight gain, polycystic ovaries, and hyperandrogenism, in bipolar adolescent females treated with LI, DVP, or LI + DVP; 3) To collect data on possible predictors of acute treatment response to the two active treatments; 4) To provide descriptive information on the stability of acute phase response to monotherapy with either LI or DVP over 16 weeks of continuation phase treatment. We will systematically collect data concerning the short- and long-term safety and tolerability of mood stabilizers in children and adolescents. No studies have looked at the question of weight gain, polycystic ovaries, and endocrine abnormalities in female bipolar adolescents treated with mood stabilizers. Because of the frequent use of mood stabilizers in bipolar adolescents, this is an important area to systematically collect prospective data on. We will also be able to provide descriptive data and effect size estimates of combined treatment with LI and DVP in patients who do not respond acutely to either one and collect data on possible predictors of acute treatment response to the two active treatments. Lastly, this trial will provide descriptive information on the stability of acute phase response to monotherapy over a 16 week continuation phase.
