A double-blind, randomized, placebo-controlled trial of divalproex extended-release in the treatment of bipolar disorder in children and adolescents

Karen Wagner, Laura Redden, Robert A. Kowatch, Timothy E. Wilens, Scott Segal, Kiki Chang, Patricia Wozniak, Namita V. Vigna, Walid Abi-Saab, Mario Saltarelli

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

OBJECTIVE:: To compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study. METHOD:: In the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 μg/mL. Sixty-six patients enrolled in the extension study. RESULTS:: In the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER -8.8 [n = 74]; placebo -7.9 [n = 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting. CONCLUSIONS:: The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study.

Original languageEnglish (US)
Pages (from-to)519-532
Number of pages14
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume48
Issue number5
DOIs
StatePublished - May 2009

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Valproic Acid
Bipolar Disorder
Randomized Controlled Trials
Placebos
Double-Blind Method
Therapeutics
Safety
Ammonia
Vomiting
Headache
Incidence

Keywords

  • Bipolar disorder
  • Divalproex ER
  • Treatment

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental and Educational Psychology

Cite this

A double-blind, randomized, placebo-controlled trial of divalproex extended-release in the treatment of bipolar disorder in children and adolescents. / Wagner, Karen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 48, No. 5, 05.2009, p. 519-532.

Research output: Contribution to journalArticle

Wagner, Karen ; Redden, Laura ; Kowatch, Robert A. ; Wilens, Timothy E. ; Segal, Scott ; Chang, Kiki ; Wozniak, Patricia ; Vigna, Namita V. ; Abi-Saab, Walid ; Saltarelli, Mario. / A double-blind, randomized, placebo-controlled trial of divalproex extended-release in the treatment of bipolar disorder in children and adolescents. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2009 ; Vol. 48, No. 5. pp. 519-532.
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