Divalproex Sodium vs Placebo for the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorders

Abstract

Objective Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterized by social and language deficits and repetitive behaviors and interests. Irritability/aggression is a significant co-morbid 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. Methods 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. Fifty five subjects signed consent and 27 were randomized in a 1:1 fashion (mean age 9.46±2.46, mean non verbal IQ 63.3±23.9). Two subjects from the active group and one subject from the placebo group discontinued the study due to either lack of efficacy or side effects (increased irritability). Results The primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement, focused on irritability. 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 the responders to have higher valproate blood levels than the non-responders. Conclusions This study suggests efficacy of divalproex for the treatment of irritability in children and adolescents with ASD. Larger sample follow-up studies are warranted.

Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis

“…12,13,[19][20][21][22][23][25][26][27]29,30,34,35,38,39,41,60 NAC, clonidine, methylphenidate, and tianeptine yielded moderate to large effect sizes. 26,27,30,38,41 In contrast to risperidone and aripiprazole, NAC, methylphenidate, and tianeptine did not cause significant somnolence, EPSs, or weight gain.…”

Autistic characteristics in adults with epilepsy

“…Continual improvements have been also found in children with autism without epilepsy even after the AEDs were discontinued (Baird, Robinson, Boyd, & Charman, 2006). A randomised, double-blind, placebo-controlled trial found that the AED 'Valproate' may be effective in the treatment of mood changes in children and adolescents with ASD (Hollander et al, 2010). The researchers suggest that improved behavioural response may be due to the treatment of underlying epileptiform abnormalities.…”

Therapeutic Potential of Everolimus on Core Autism Symptoms and Increasing Serum Ceruloplasmin and Transferrin Levels in a Pubescent Boy with Tuberous Sclerosis

“…The SCQ is measure for parents/caregivers to assess their child's reciprocal social interaction, communication, and repetitive, stereotyped domains [17] based on the ADI-R. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC). The ABC is primarily intended to evaluate treatment responses in psychopharmacological and behavioral intervention trials for children and adolescents with mental retardation [19] and normal IQ levels [20].…”