Divalproex Monotherapy in the Treatment of Bipolar Offspring With Mood and Behavioral Disorders and at Least Mild Affective Symptoms

Background: Offspring of parents with bipolar disorder, by virtue of their high-risk status for developing bipolar disorder, merit an investigation of the efficacy of treatment with mood stabilizers. Behavioral and mood difficulties in this population may represent prodromal forms of bipolar disorder. We studied the efficacy of divalproex in treating child and adolescent bipolar offspring with mood or behavioral disorders who did not yet meet criteria for bipolar I or II disorder.

Method: We studied 24 children aged 6-18 years (mean = 11.3 years; 17 boys/7 girls) with at least 1 biological parent with bipolar disorder. Participants were diagnosed by the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia with at least 1 of the following DSM-IV disorders: major depressive disorder, dysthymic disorder, cyclothymic disorder, or attention-deficit/hyperactivity disorder. Subjects all had at least moderate affective symptoms (28-item Hamilton Rating Scale for Depression or Young Mania Rating Scale score > 12). After a 2-week washout period, subjects were treated with divalproex for 12 weeks, titrated to achieve serum levels of 50-120 mg/mL (mean final dose = 821 mg/day; mean final serum level = 79.0 mg/mL).

Results: One subject discontinued after 2 weeks due to continuation of symptoms. Of the remaining 23 subjects, 18 (78%) were considered responders by primary outcome criteria (“very much improved” or “much improved” on the Clinical Global Impressions-Improvement scale). Divalproex was well tolerated with no discontinuations due to adverse effects.

Conclusion: Bipolar offspring with mood or behavioral disorders and at least mild affective symptoms may respond to divalproex treatment. Our study was limited by the open treatment, lack of a placebo group, and the heterogeneous nature of the sample. Controlled studies are warranted in the use of divalproex in symptomatic bipolar offspring.