An Open Trial of Divalproex Sodium in Autism Spectrum Disorders

Background: Autism spectrum disorders are characterized by core deficits in social interaction and speech/communication skills, repetitive behaviors, and restricted interests. Other abnormalities include seizures, electroencephalographic (EEG) abnormalities, affective instability, impulsivity, and aggression. Divalproex sodium is indicated as both an anticonvulsant in epilepsy and a mood stabilizer in bipolar illness and thus might be useful for these complicating symptoms in autism.

Method: A retrospective pilot study was conducted to determine whether divalproex sodium was effective in treating core dimensions and associated features of autism. Fourteen patients who met DSM-IV criteria for autism, Asperger’s disorder, or pervasive developmental disorder not otherwise specified, both with and without a history of seizure disorders or EEG abnormalities, were openly treated with divalproex sodium. Improvement was assessed via the Clinical Global Impressions-Improvement scale.

Results: Of 14 patients who completed a trial of divalproex sodium, 10 (71%) were rated as having sustained response to treatment. The mean dose of divalproex sodium was 768 mg/day (range, 125-2500 mg/day), and it was generally well tolerated. Improvement was noted in core symptoms of autism and associated features of affective instability, impulsivity, and aggression.

Conclusion: Divalproex sodium may be beneficial to patients with autism spectrum disorders, particularly those with associated features of affective instability, impulsivity, and aggression as well as those with a history of EEG abnormalities or seizures. Of note, all patients with an abnormal EEG and/or seizure history were rated as responders. However, these findings must be interpreted with caution, given the open retrospective nature of the study. Controlled trials are needed to replicate these preliminary findings.