Valproate for the treatment of irritability/aggression in child autism

Background:

Aggression, both self- and other-directed, is a common associated feature of autism, as is irritability.  Several atypical antipsychotics, particularly risperidone, have demonstrated efficacy for the treatment of irritability / aggression in children with autism.  However, the use of such medications has been associated with side effects such as weight gain that may increase the likelihood of diabetes and cardiovascular disease, sedation and movement disorders.

Objectives: This study examines the effect of valproate in the treatment of irritability/ aggression in children with autism via a 12 week, double-blind placebo-controlled trial.

Methods:

Twenty seven  children ages 5-17 were randomized to valproate vs placebo. Diagnosis was confirmed by ADI-R and ADOS-G.  Inclusion criteria included evidence of significant irritability (ABC irritability score >17 or OAS-M score >12). Subjects were followed biweekly and safety blood work was performed at weeks 0, 2, 4, and 12.

Results:

Ten of the 16 active treatment subjects (62.5%) showed a response on impulsive aggression/irritability, whereas only 1 of the placebo subjects (9.09%) showed a response (odds ratio =16.66). This effect is significant by Fisher’s exact test (p = .008). There is a significant weeks x condition interaction (p = .048) suggesting that there is an additional drop of .53 points/week on the ABC Parent Irritability Ratings in the treatment condition compared to the placebo condition.  The significant condition x weeks interaction remains significant after controlling for the IQ differences (t=-2.28, df=20.38, p=0.033). Exploratory analysis suggests that children with epileptiform baseline EEGs are more likely to be categorized as responders.  The medication was well tolerated. 

Conclusions:

This data supports the use of valproate for the treatment of irritability/aggression in children with autism.  Further larger trials are necessary to confirm this early finding and to further examine the relationship of baseline epileptiform abnormalities and response to treatment.