Objectives: Autism is a severe neurodevelopmental disorder affecting 1 in 166 children. There
are currently no approved medications for either core or associated symptoms of autism.
In this study the effect of divalproex sodium vs. placebo on irritability in children
with autism was examined in a double blind placebo controlled fashion.
Methods: Twenty-six children with autism and significant irritability (ABC irritability subscore=18)
were randomized to divalproex sodium vs. placebo and followed for 12 weeks. Outcome
measures included CGI-I, Overt Aggression Scale – Modified (OAS-M) and the Aberrant
Behavior Scale (ABC).
Results: There was statistically significant improvement in irritability in subjects treated
with divalproex sodium vs. placebo as measured by the CGI-I (p=0.002, d=1.46) and
the Irritability subscale of the OAS-M (p=0.026). Significant improvements were also
noted in aggression as measured by the “assault against objects” subscore of the OAS-M
(p=0.005) and the irritability subscale of the ABC (teacher rating) (p=0.05). The
medication was well tolerated.
Conclusions: Divalproex sodium was very effective in reducing irritability in our sample of children
with autism and is a promising agent for the treatment of irritability in this population.
