Divalproex Sodium/Placebo In Child/Adolesent Autism

Project: Research project

Project Details


DESCRIPTION (provided by applicant): Autism is a pervasive developmental
disorder affecting social, communicative, and repetitive behavior domains and
cognitive function, and has dramatic impact on quality of life. It is also
frequently accompanied by aggression, self-injury, impulsivity, and mood
instability, as well as EEG abnormalities and seizure disorders. While large
scale studies of childhood autism are currently underway with SSRI's and
atypical neuroleptics, little controlled data is available with other agents
that might target these core and associated symptoms of autism. This
application aims to determine whether there is scientific evidence to support
the practice of prescribing divalproex sodium (DS)(valproate) to
child/adolescent autistic patients. When a medication is used extensively prior
to scientific substantiation in controlled clinical trials, the consequences
can sometimes be problematic. Neither the side effects nor efficacy of
valproate in treating child/adolescent autistic disorders has been definitively
established. Of theoretical interest, valproate has possible neuroprotective
effects mediated by signal transduction pathways (i.e., protein kinase-c
inhibition and bcl-2 activation) which may potentially be beneficial for a
neurodevelopmental disorder such as autism.

This study is the first double-blind placebo-controlled medication trial of
valproate for children and adolescents with autism, and utilizes a 12-week
double-blind placebo-controlled parallel design. The study is unique in
examining the treatment effects of valproate (DS) versus placebo on global
autism severity; aggression, self-injury and impulsivity; affective
instability; repetitive behaviors and social deficits; and functional ability.
While our pilot open data evaluating the use of DS for autistic subjects has
been encouraging so far (71 percent of autistic subjects were global treatment
responders on open DS), a double blind placebo controlled trial with larger
sample size and more precise methodology is needed to provide a scientifically
sound conclusion about the efficacy, side effects, and effects on functional
living skills of this medication in children with autism. This will
definitively either support or contradict its widespread use in this
understudied and neglected population, and provide a benchmark by which new
treatments could be compared. It will also assess the relationship between dose
and blood levels and response, potentially identify subgroups particularly
responsive to this treatment, and identify which components and associated
symptoms are most responsive to change.
Effective start/end date9/30/018/31/06


  • Psychiatry and Mental health


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