title: 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.affiliation: Department of Psychiatry, Montefiore Medical Center University Hospital for Albert Einstein College of Medicine, Child Psychiatry Annex, Bronx, NY 10467-2490, USA. eholland@montefiore.org
authors.forename: Eric
authors.initials: E
authors.lastname: Hollander
authors.forename: William
authors.initials: W
authors.lastname: Chaplin
authors.forename: Latha
authors.initials: L
authors.lastname: Soorya
authors.forename: Stacey
authors.initials: S
authors.lastname: Wasserman
authors.forename: Sherry
authors.initials: S
authors.lastname: Novotny
authors.forename: Jade
authors.initials: J
authors.lastname: Rusoff
authors.forename: Nicole
authors.initials: N
authors.lastname: Feirsen
authors.forename: Lauren
authors.initials: L
authors.lastname: Pepa
authors.forename: Evdokia
authors.initials: E
authors.lastname: Anagnostou
mesh_terms: D000293:Adolescent; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002653:Child Behavior Disorders / Q000188:drug therapy* / Q000209:etiology; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy* / Q000503:physiopathology*; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects; D008297:Male; D010552:Personality Assessment; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D014635:Valproic Acid