Extended Oxytocin Treatment of Children with Autistic Disorder

Background: Animal studies have demonstrated that oxytocin is important in regulating affilliative and nurturing behaviors in some species and that administration of a single dose of oxytocin to nonhuman primates enhances generosity and awareness of social hierarchies.  Single doses of oxytocin in adults and adolescents with autism have been demonstrated to improve awareness of social behaviors and recognition of emotion.   In adults with Fragile X, a single 24 IU dose of oxytocin improved eye contact.  However, no clinical trials have yet examined the effects of repeated doses of oxytocin given for a sustained period of time in children with autism.

Objectives: Our aim was to determine if extended treatment with intranasal oxytocin would be tolerated by children with autism across the pediatric age range and to characterize any changes in social functioning associated with treatment. 

Methods: We randomly assigned children ages 3 to 17 years with autistic disorder (DSM IV 299.0) confirmed by ADOS to 8 weeks of twice daily (AM and afternoon) treatment with flexibly dosed intranasal oxytocin or matched placebo.    Subsequently, all participants received twice daily oxytocin for 8 weeks.  Participants were assessed with the Aberrant Behavior Checklist (ABC), the Social Reciprocity Scale(SRS), the Pervasive Developmental Behavior Inventory (PDD BI), the Vineland Adaptive Behavior Scales – 2 and Stanford-Binet.  Adverse events were systematically elicited. 

Results: 25 children, mean age 10.3 ± 4.4 (SD) years, were randomized: 12 to oxytocin and 13 to placebo.  Eleven children were nonverbal and fourteen had fluent speech.  Oxytocin was well tolerated with the exception of one participant who withdrew within 2 weeks of treatment with oxytocin due to worsening insomnia and agitation.  Worsening oppositionality, aggression, irritability, poor concentration and gastrointestinal disorders were all more common during the course of placebo treatment than oxytocin treatment.  Those treated with oxytocin showed reductions in many, but not all, measures of social functioning: ABC-Social Withdrawal -2.0(1.0 SE) with oxytocin versus -1.3(1.8) with placebo; PDD-BI Social Deficit Score -2.8(1.6) with oxytocin versus -1.5(2.0)with placebo; SRS Awareness -4.4(2.9) with oxytocin versus -2.1(3.9) with placebo, SRS Motivation -5.8(3.9) with oxytocin versus -2.1(3.5) with placebo, SRS total -5.1(2.3) with oxytocin versus -3.9(3.3) with placebo.  They also had a significant reduction in ABC-Irritability: -3.4(0.9) with oxytocin  versus -1.7(1.7) with placebo. Benefits continued to acrue during the 8 weeks of open oxytocin treatment.

Conclusions:  Oxytocin was well tolerated by most children in the trial over 8 weeks of sustained treatment.  It appeared to have benefit for reducing irritability and improving some aspects of social functioning.  Larger scale trials of sustained intranasal oxytocin treatment in children with autism are needed to fully evaluate its safety and establish its efficacy for improving social functioning.