Long-term safety of divalproex sodium extended-release in children and adolescents with bipolar I disorder.
OBJECTIVE
The objective of this open-label study was to assess the safety of divalproex sodium extended-release in the treatment of children and adolescents with acute mania associated with bipolar I disorder.


METHODS
This was a 6-month, Phase 3, open-label study in healthy subjects aged 9-17 years with a current Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder manic or mixed episode. Divalproex sodium extended-release (DVPX-ER) was initiated at 15 mg/kg per day on day 1 (not to exceed 750 mg/day) with increases allowed to a maximum of 35 mg/kg per day. Study visits were conducted on day 1 and at months 1, 2, 3, and 6. Assessments included standard safety evaluations and appropriate rating scales for clinical effect.


RESULTS
A total of 226 subjects were enrolled; 109 subjects completed the study. The most common adverse events were weight gain (16%), nausea (9%), and increased appetite (8%). Nonsymptomatic elevations of mean ammonia levels in plasma were observed. The mean Young Mania Rating Scale (YMRS) decreased 12.4 from baseline to final visit; small improvements were seen in behavior and caregiver stress ratings.


CONCLUSIONS
DVPX-ER was generally well tolerated in children and adolescents with acute mania, with a side-effect profile similar to that observed in adults.
Redden
Laura
L
Abbott, Abbott Park, Illinois 60064, USA. Laura.Redden@abbott.com
DelBello
Melissa
M
Wagner
Karen Dineen
KD
Wilens
Timothy E
TE
Malhotra
Shishuka
S
Wozniak
Patricia
P
Vigna
Namita V
NV
Greco
Nicholas
N
Kovacs
Xenia
X
Abi-Saab
Walid
W
Saltarelli
Mario
M
D000293:Adolescent; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
D018692:Antimanic Agents; D003692:Delayed-Action Preparations; D014635:Valproic Acid