Divalproex sodium vs placebo for the treatment of irritability in children and adolescents with autism spectrum disorders.

Abstract

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests. Irritability/aggression is a significant comorbid symptom in this population, which greatly impacts burden of care. This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD. This was a 12-week randomized, double-blind, placebo-controlled trial. All efficacy measures were obtained by an independent evaluator blinded to randomization condition and side effects. A total of 55 subjects gavetheir consent and 27 were randomized in a 1 : 1 manner (mean age 9.46+/-2.46, mean nonverbal IQ 63.3+/-23.9). Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects (increased irritability). Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement, which focused on irritability. Overall, 62.5% of divalproex subjects vs 9% of placebo subjects were responders (CGI-irritability OR: 16.7, Fisher's exact p=0.008). A statistically significant improvement was also noted on the ABC-Irritability subscale (p=0.048). There was a trend for responders to have higher valproate blood levels compared with nonresponders. This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD. Larger sample follow-up studies are warranted.

• Authors: Eric Hollander, William Chaplin, Latha Soorya, Stacey Wasserman, Sherry Novotny, Jade Rusoff, Nicole Feirsen, Lauren Pepa, Evdokia Anagnostou
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 35 Issue 4 Pg. 990-8 (Mar 2010) ISSN: 1740-634X [Electronic] England
• PMID: 20010551 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antimanic Agents
• Valproic Acid

Topics

• Adolescent
• Antimanic Agents (pharmacology, therapeutic use)
• Child
• Child Behavior Disorders (drug therapy, etiology)
• Child Development Disorders, Pervasive (drug therapy, physiopathology)
• Child, Preschool
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Irritable Mood (drug effects)
• Male
• Personality Assessment
• Psychiatric Status Rating Scales
• Treatment Outcome
• Valproic Acid (pharmacology, therapeutic use)