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


METHODS
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.
Wagner
Karen Dineen
KD
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.
Redden
Laura
L
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.
Kowatch
Robert A
RA
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.
Wilens
Timothy E
TE
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.
Segal
Scott
S
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.
Chang
Kiki
K
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.
Wozniak
Patricia
P
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.
Vigna
Namita V
NV
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.
Abi-Saab
Walid
W
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.
Saltarelli
Mario
M
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.