An Open-Label Trial of Divalproex in Children and Adolescents with Bipolar Disorder

Objective: This study evaluated the safety and effectiveness of divalproex sodium (Depakote®) in the treatment of youths with bipolar disorder. Method: Forty bipolar disorder patients aged 7 to 19 years, with a manic, hypomanic, or mixed episode, enrolled in an open-label study of divalproex (2-8 weeks), followed by a double-blind, placebo-controlled period (8 weeks). Results: Twenty-two subjects (61%) showed ≥50% improvement in Mania Rating Scale (MRS) scores during the open-label period. Significant (p < .001) improvements from baseline were seen for mean scores of all efficacy measures, including the MRS, Manic Syndrome Scale, Behavior and Ideation Scale, Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, and Hamilton Rating Scale for Depression. Of the 23 subjects who discontinued the study during the open-label period, 6 (15%) discontinued for ineffectiveness, 6 (15%) for intolerance, 6 (15%) for noncompliance, and 6 (15%) for other reasons. Adverse events were generally mild or moderate in severity, with the most common being headache, nausea, vomiting, diarrhea, and somnolence. Laboratory data results were unremarkable. Too few subjects participated in the double-blind period for statistical analysis. Conclusion: This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths.