6.14 Randomized, Placebo-Controlled Trial With Open-Label Extension of Intranasal Oxytocin for Autism Spectrum Disorder

Abstract

The neuropeptide oxytocin (OXT) plays an important role in human social behaviors. There is growing interest in the use of OXT for mental health conditions characterized by social impairment. Studies of adult populations with autism spectrum disorder (ASD) have shown promising responses in social cognition, quality of life, and repetitive behaviors. To date, few studies have examined the safety and tolerability of the sustained use of OXT in a pediatric population with ASD. None have comprehensively elicited adverse events, monitored cardiac function, or collected routine blood chemistries in a systematic way to evaluate the safety of intranasal OXT. In order to investigate the safety, tolerability, and potential efficacy of sustained, daily administration of OXT in children with ASD, we conducted a randomized, double-blind, placebo-controlled crossover pilot study in 25 youths aged 3 to 17 years. Intranasal administration of flexibly dosed oxytocin or placebo was provided for 8 weeks; then an additional 8 weeks of open-label oxytocin was given to all participants. All screened participants (n = 27) were recruited through the University of North Carolina at Chapel Hill. OXT treatment was well tolerated with the exception of a single subject. One in 12 subjects randomized to OXT discontinued during blind treatment, and 2 in 24 discontinued during open treatment. Adverse events were comparable between the oxytocin and placebo groups. All safety assessments including EEG and blood chemistry revealed no clinically significant differences between OXT and placebo. Secondary efficacy assessments indicated that significant within-group changes were observed after 8 weeks on the Aberrant Behavior Checklist (ABC)-Social Withdrawal, ABC-Irritability, and ABC-Stereotypy subscales (3 variables: all p < 0.05) in the OXT group. Findings in this study must be interpreted in the context of several limitations. Most prominent are the small sample size and multiple assessments. The primary goal of this study was to evaluate the safety and tolerability of a treatment that may be used for months if not years in a pediatric population. Our small pilot sample would likely miss uncommon but serious adverse events. Future studies must be powered and of sufficient duration to explore the long-term safety and tolerability of OXT.