Double-blind, placebo-controlled trial of divalproex monotherapy in the treatment of symptomatic youth at high risk for developing bipolar disorder.

OBJECTIVE To determine if divalproex sodium was superior to placebo in the treatment of symptomatic youths who suffer from a bipolar spectrum disorder and who also have a parent with a diagnosis of a bipolar illness. METHOD Youths, ages 5 to 17 years, meeting DSM-IV criteria for bipolar disorder not otherwise specified (NOS) or cyclothymia who also had at least 1 biological parent with bipolar illness were randomly assigned in a double-blind fashion to receive treatment with either dival-proex sodium or placebo for up to 5 years. Study participation ended if the subject required additional clinical intervention, if the patient developed treatment-related adverse events, or if the participant was not adherent with study procedures. The primary outcome measure was time to study discontinuation for any reason. The study was conducted from August 1997 to April 2003. RESULTS Fifty-six youths with a mean (SD) age of 10.7 (3.1) years were randomly assigned and received either divalproex sodium (N = 29) or placebo (N = 27). In spite of statistical power of 80% to detect hazard ratios of 2.2 or larger, the treatment groups did not significantly differ in survival time for discontinuation for any reason (p = .93) or discontinuation due to a mood event (p = .55). Changes in mood symptom ratings and psychosocial functioning from baseline to study discontinuation did not differ between groups (most significant p > .14). However, both groups did show improvements in mood symptoms and psychosocial functioning over time (all p values < .002). One patient, from the placebo group, ended study participation due to an adverse event. CONCLUSION These results suggest that, although well tolerated, divalproex sodium does not produce clinically meaningful improvements in the treatment of symptomatic youths suffering from either bipolar NOS or cyclothymia who are at genetic risk for developing bipolar disorder.