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J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):519-532. doi: 10.1097/CHI.0b013e31819c55ec.

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

Author information

1
Dr. Wagner is with the University of Texas Medical Branch; Dr. Redden is with the Abbott Laboratories; Dr. Kowatch is with the University of Cincinnati Medical Center; Dr. Wilens is with the Massachusetts General Hospital; Dr. Segal is with the Segal Institute for Clinical Research; Dr. Chang is with the Stanford University School of Medicine; Drs. Vigna, Abi-Saab, and Saltarelli are with Abbott Laboratories and the Divalproex ER Pediatric Mania Group; and Dr. Wozniak is with Advanced Clinical Research Services. Electronic address: kwagner@utmb.edu.
2
Dr. Wagner is with the University of Texas Medical Branch; Dr. Redden is with the Abbott Laboratories; Dr. Kowatch is with the University of Cincinnati Medical Center; Dr. Wilens is with the Massachusetts General Hospital; Dr. Segal is with the Segal Institute for Clinical Research; Dr. Chang is with the Stanford University School of Medicine; Drs. Vigna, Abi-Saab, and Saltarelli are with Abbott Laboratories and the Divalproex ER Pediatric Mania Group; and Dr. Wozniak is with Advanced Clinical Research Services.

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 microg/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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00067262 NCT00195767.

PMID:
19325497
DOI:
10.1097/CHI.0b013e31819c55ec
[Indexed for MEDLINE]

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