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.


METHODS
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.


CONCLUSIONS
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.
Hollander
E
E
Department of Psychiatry and Seaver Autism Research Center, Mt. Sinai School of Medicine, New York, NY 10029-6574, USA. eric.hollander@mssm.edu
Dolgoff-Kaspar
R
R
Cartwright
C
C
Rawitt
R
R
Novotny
S
S
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D020817:Asperger Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D001321:Autistic Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002065:Buspirone / Q000627:therapeutic use; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D002065:Buspirone; D017367:Selective Serotonin Reuptake Inhibitors; D014635:Valproic Acid