title: Long-term safety of divalproex sodium extended-release in children and adolescents with bipolar I disorder.
abstract: 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.
authors.affiliation: Abbott, Abbott Park, Illinois 60064, USA. Laura.Redden@abbott.com
authors.forename: Laura
authors.initials: L
authors.lastname: Redden
authors.forename: Melissa
authors.initials: M
authors.lastname: DelBello
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Wilens
authors.forename: Shishuka
authors.initials: S
authors.lastname: Malhotra
authors.forename: Patricia
authors.initials: P
authors.lastname: Wozniak
authors.forename: Namita V
authors.initials: NV
authors.lastname: Vigna
authors.forename: Nicholas
authors.initials: N
authors.lastname: Greco
authors.forename: Xenia
authors.initials: X
authors.lastname: Kovacs
authors.forename: Walid
authors.initials: W
authors.lastname: Abi-Saab
authors.forename: Mario
authors.initials: M
authors.lastname: Saltarelli
mesh_terms: 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*
chemical_list: D018692:Antimanic Agents; D003692:Delayed-Action Preparations; D014635:Valproic Acid