Divalproex Versus Placebo for the Prevention of Irritability Associated With Fluoxetine Treatment in Autism Spectrum Disorder
Autism is a developmental disorder characterized by social and communication deficits, and restrictive/repetitive patterns of behavior. It severely impacts the affected individual and family members, and causes life-long functional impairment. Available treatments aim to alleviate some of the core and associated symptoms of autism. Well-controlled data has established the effectiveness of divalproex sodium in treating aggression and affective instability in other populations, and open data have demonstrated its usefulness for aggression in autistic subjects.1-3 The presumed mechanism of action is related to elevation of γ-amino butyric acid (GABA) levels in the central nervous system, but epigenetic modification of GAD67 and reelin genes has also been proposed.4 Multiple well-controlled trials have also shown serotonin reuptake inhibitors to be moderately effective in the treatment of repetitive behaviors in children with autism.5 However, treatment with these medications may be accompanied by behavioral activation, including symptoms such as irritability. These adverse effects may outweigh benefits and lead to discontinuation of treatment in some patients.6
This study aimed to generate pilot data testing the hypothesis that pretreatment with divalproex sodium versus placebo decreases the irritability experienced by autistic individuals in association with fluoxetine treatment.