Discussion
autistic, autism
ADVERSE EVENTS
The results of this study showed there was no overall benefit of oxytocin treatment for children with autism. Despite this, there was some evidence to suggest that younger children showed greater improvements on social responsiveness at the end of oxytocin treatment, in comparison to placebo. There was no evidence of any benefit from oxytocin treatment to older autistic children, nor was there evidence that observed benefit in the younger age group was maintained following treatment discontinuation. In regards to placebo treatment, this study showed consistent, small to moderate effect sizes of improvement from placebo treatment across measures during the placebo lead-in phase. These effects dissipated during the second phase of placebo treatment (i.e., from Visit 2 to Visit 3 in the placebo group) to support the effectiveness of the placebo washout. In terms of safety, oxytocin nasal spray was well tolerated. There were no serious adverse events linked to oxytocin administration. Interestingly, a greater number of placebo-administered participants reported adverse events in comparison to oxytocin.While some studies have suggested benefits of oxytocin to younger children [Previous studies have also highlighted the potential of placebo-based responses to provide therapeutic outcomes across many clinical conditions [While the safety of oxytocin treatment for children has been debated [We note limitations of the current study, including a moderate sample size, the inclusion of participants on other psychotropic medications that were stabilized before drug assignment, and reliance on a caregiver and clinician reports as outcome measures. The development of sensitive observational and other markers of change for use in autism clinical trials remains an ongoing priority [In conclusion, the results of this study showed that younger children may benefit from oxytocin nasal spray in comparison to placebo, as indicated by change on caregiver-rated social responsiveness. Oxytocin treatment was found to be well tolerated, with more adverse events reported in the placebo condition. There was evidence of a moderately sized placebo effect across measures in the trial. This study provides one of the first studies in the autism field to demonstrate the benefit of a placebo lead-in phase for clinical trials. There is now a pressing need to conduct larger studies that can definitively test whether younger children benefit from oxytocin, to better disentangle placebo-based effects, and to determine whether oxytocin can be used to enhance social learning circuits. There is also a great need to identify biological pathways underpinning oxytocin uptake, and to identify objective markers of treatment response, in order to better understand how oxytocin may be appropriately used.