The rationale, design, and progress of two novel maintenance treatment studies in pediatric bipolarity

Introduction: There are no definitively established acute or maintenance treatments for juvenile bipolar disorder. Method: Two randomized, blind, maintenance clinical trials in children and adolescents with bipolar disorders are ongoing at the University Hospitals of Cleveland/Case Western Reserve University Stanley Clinical Research Center for bipolar disorder. The first is comparing the safety and effectiveness of lithium carbonate (Li+) to divalproex sodium (VPA) for up to 76 weeks in youths with stabilized bipolar illness (type 1 or 2). The second study is designed to compare the efficacy of VPA to placebo in the acute management of subsyndromal symptoms of bipolar disorder ('cyclotaxia') and the prevention of the full syndrome in children at risk. Both studies use the prospective life-chart method as an outcome measure. Results: Sixty-six youths have received study medication as part of the trial that is comparing Li+ to VPA as a maintenance therapy. In addition, 32 youths have received blinded treatment as part of the 'cyclotaxia' prevention study. Combination Li+/VPA treatment appears generally well tolerated and seems to have robust anti-manic and antidepressant effects. Discussion: Since the blind has not been broken on either of these clinical trials, conclusions about the maintenance effectiveness of either VPA or Li+ in youths with bipolar disorder type 1 or 2 cannot be made yet. Similarly, it is unclear whether VPA is superior to placebo in genetically high-risk youths with cyclotaxia. The final results of these trials should provide valuable information about the treatment of juvenile bipolar disorders.