Divalproex Monotherapy in the Treatment of Bipolar Offspring With Mood and Behavioral Disorders and at Least Mild Affective Symptoms
J Clin Psychiatry 2003;64:936-942
© Copyright 2014 Physicians Postgraduate Press, Inc.
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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
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
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.