A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research

Abstract

In this article, we conduct a comprehensive review of existing evidence for the safety and therapeutic potential of intranasal oxytocin in pediatric populations. Unique considerations for dosing and delivery of oxytocin to the nasal passageway in pediatric populations and methods to promote adherence are reviewed. Intranasal oxytocin has been administered to 261 children in three open-label studies and eight randomized controlled trials. To date, the only published results in pediatric populations have focused on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Results regarding efficacy for improving social impairment in ASD are equivocal, partially due to mixed methodological designs, dosing regimens, and outcome measures. At present, there is no randomized controlled evidence that oxytocin provides benefit to individuals with PWS. There is no clear evidence of a link between oxytocin administration and any specific adverse event. Adverse events have been assessed using medical interviews, open reports, checklists, and physiological assessments. Adverse events reports have been largely classified as mild (n = 93), with few moderate (n = 9) or severe (n = 3) events reported. There were 35 additional adverse events reported, without severity ratings. Severe events, hyperactivity and irritability, occurred at first administration in both placebo and oxytocin groups, and subsided subsequent to discontinuation. We note that adverse event monitoring is inconsistent and often lacking, and reporting of its relationship to the study drug is poor. Only one study reported adherence data to suggest high adherence. Recommendations are then provided for the delivery of nasal sprays to the nasal passageway, monitoring, and reporting of efficacy, safety, and adherence for oxytocin nasal spray trials in pediatric populations.

Binding Characteristics of Two Oxytocin Variants and Vasopressin at Oxytocin Receptors from Four Primate Species with Different Social Behavior Patterns

“…Synthetic OT is used widely in clinical settings for inducing and accelerating labor. Because of its ability to modulate a wide variety of social behaviors (Lee et al, 2009), OT is currently being evaluated for its clinical use in disorders with a social component, such as autism spectrum disorder and schizophrenia (Bakermans-Kranenburg and van Ijzendoorn, 2013;Feifel et al, 2016;DeMayo et al, 2017;Parker et al, 2017). Considerable effort has been invested in engineering OT analogs and formulations for potential therapeutic use and to extend understanding of OT actions, particularly central nervous system and behavioral effects (Manning et al, 2012;Busnelli et al, 2013;Muttenthaler et al, 2017).…”

Stem cell therapy in autism: recent insights

“…After 6 months of cellular therapy, improvements in concentration, sitting tolerance, attention, sleep, eye contact, social interactions, and memory were reported, as measured by ISAA, CARS, and Functional Independence Measure scores before and after cellular treatment. Six months posttherapy, 18 F-FDG PET scan showed improvements in brain hypometabolism.…”

“… 17 Hormonal therapies with oxytocyin have also shown some promises in improving central ASD symptoms. 18 The use of vitamins, herbals, essential oils, and nutritional supplements 19 , 20 and conventional therapies have some effect in symptomatic improvement in ASD, though additional studies are needed to confirm these benefits. Developing novel therapies may prove to be the ultimate intervention for sustained improvement of symptoms in ASD.…”

“…CGI scale scored changes in the severity of the disease, overall improvement, and the efficacy of the treatment. Interestingly, functional neuroimaging, by the means of positron emission tomography (PET) scan, showed increased 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in the areas of frontal lobe, cerebellum, amygdala, hippocampus, parahippocampus, and mesial temporal lobe after 6 months of cellular therapy. Hypoperfusion has been recently demonstrated in key brain areas of ASD subjects.…”

Does perinatal exposure to exogenous oxytocin influence child behavioural problems and autistic‐like behaviours to 20 years of age?

“…A confluence of recent evidence has demonstrated that OT nasal spray enhances social cognition by improving social recognition, encoding of social memories, retrieval of social cues, and accurate and positive appraisal of social information at various levels of processing (Guastella & MacLeod, ), including in young children with autism (Yatawara, Einfeld, Hickie, Davenport, & Guastella, ). While there is consistent evidence suggesting the short‐term safety of oxytocin administration to paediatric populations (DeMayo, Song, Hickie, & Guastella, ), recent commentaries on the use of intranasal OT have argued for caution in regards to possible longer term effects on social development, particularly when exogenous administration is provided very early in life (Miller, ). Oxytocin is able to cross the placenta, and it has been argued that the transmission of exogenous OT to the foetus in this early phase of development may cause deleterious impacts on long‐term social and emotional development (Carter, ).…”