Infrequent intranasal oxytocin followed by positive social interaction improves symptoms in autistic children: a randomized clinical trial

There are currently no approved drug interventions for social behavior dysfunction in autism spectrum disorder (ASD). Previous trials investigating effects of daily intranasal oxytocin treatment have reported inconsistent results and have not combined it with positive social interaction. However, In two preclinical studies we established that treatment every-other-day rather than daily is more efficacious in maintaining neural and behavioral effects by reducing receptor desensitization. We aimed to establish whether 6-weeks of intranasal oxytocin compared with placebo treatment, followed by a period of positive social interaction, would produce greater symptom improvements in children with ASD. A double-blind, randomized, cross over design trial was completed including 41 children with ASD aged 3-8 years. Primary outcomes were the Autism Diagnostic Observation Schedule-2 (ADOS-2) and social responsivity scale-2 (SRS-2). Secondary measures included other autism-related questionnaires and social attention assessed using two eye-tracking paradigms. A clinical reliable change index analysis revealed improvements in ADOS-2 total scores in 44% of children. Improvements in SRS-2 and behavioral adaptability scores were also found and correlated with increased basal saliva oxytocin concentrations. Additionally, oxytocin improved restrictive and repetitive behavior scores and increased time spent viewing dynamic social compared to geometric stimuli and the eye region of angry, happy and neutral expression faces. There were no adverse side-effects of oxytocin treatment. Overall, our results demonstrate that 6 weeks of intranasal oxytocin treatment administered every other day and followed by positive social interactions can improve clinical, eye-tracking and questionnaire-based assessments of symptoms in young autistic children.