Effects of multiple-dose intranasal oxytocin treatment on social responsiveness in children with autism: A randomized, placebo-controlled trial

Abstract

In the past decade, intranasal administration of the neuropeptide oxytocin is increasingly explored as a new treatment for reducing the core symptoms of autism spectrum disorder (ASD). The efficacy of continual oxytocin treatment in school-aged children with ASD is, however, not well established. Using a double-blind, randomized, placebo-controlled, parallel design, the current trial explored the effects of four weeks of intranasal oxytocin treatment (12 IU, twice daily) on social functioning in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). The double-blind phase was followed by a four-week single-blind extension phase during which all participants received intranasal oxytocin. In the double-blind phase, no treatment-specific effects were identified in the primary outcome assessing social functioning (parent-rated Social Responsiveness Scale), as well as on secondary outcomes assessing repetitive behaviors, anxiety, and attachment. Exploratory moderator analyses revealed that children who received the oxytocin treatment in combination with concomitant psychosocial treatment displayed a greater benefit than those who received psychosocial treatment or oxytocin alone. A modulating effect of parents’ beliefs about allocated treatment was also identified, indicating that parents who believed their child assigned to the active treatment reported greater benefit than those who believed their child received placebo, particularly in the actual oxytocin group. Finally, participants who were allocated to receive the placebo treatment during the double-blind phase of the trial and later crossed-over to receive the active treatment during the single-blind extension phase, displayed a significant within-group improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. While no overall treatment-specific improvements were identified, our results provide important indications that clinical efficacy can be augmented when oxytocin administration is paired with targeted psychosocial interventions that similarly stimulate socio-communicative behaviors. Future trials are urged to further elucidate the potential of embedding oxytocin treatment within a socially stimulating context.

At the head and heart of oxytocin’s stress-regulatory neural and cardiac effects: a chronic administration RCT in children with autism

“…In a recent combinatory trial, significant clinical improvements in social functioning were observed in young children with ASD receiving oxytocin in combination with standardized parent-child social interactions, held within the two hours after the daily nasal spray administrations 15 . These and other observations 19,54 therefore prompt future trials to administer the daily doses of chronic oxytocin administrations within more standardized contexts, e.g. by pairing them with psychosocial trainings.…”

“…Children with a formal diagnosis of ASD were recruited through the Autism Expertise Centre at the Leuven University Hospital between July 2019 and January 2021 (Figure 1, Table 1). The diagnosis was established by a multidisciplinary neuropediatric team based on the strict criteria of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) 1 . Prior to randomization, the Autism Diagnostic Observation Schedule (ADOS-2) 39 and estimates of intelligence (four subtests of the Wechsler Intelligence Scale for Children, Fifth Edition, Dutch version) 40 were acquired (Table 1).…”

“…Intranasal administration of the neuropeptide oxytocin is increasingly considered as a novel approach for alleviating disabilities associated with an autism spectrum disorder (ASD) diagnosis, including difficulties in social communication and interaction, and restricted and repetitive behaviors and interests 1 .…”

“…Recent multiple-dose, chronic administration studies have yielded a more mixed pattern of effects, with some studies showing beneficial clinical effects [9][10][11][12][13][14][15] , while others identified no benefit of oxytocin over placebo nasal spray administration [16][17][18][19] .…”

Can repeated intranasal oxytocin administration affect reduced neural sensitivity towards expressive faces in autism? A randomized controlled trial

“…As registered at the European Clinical Trial Registry (https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE), the EEG recordings were part of a larger assessment protocol, evaluating clinical efficacy of OT administration on distinct autism symptoms questionnaires, including the parent‐rated Social Responsiveness Scale‐Children, second edition (SRS‐2; Constantino & Gruber, 2012) as primary behavioural outcome, see Daniels et al. (2023) for a detailed report. In short, in terms of behavioural assessments, no OT‐specific improvements were identified, since both the OT and the placebo group displayed significant behavioural improvements in constructs assessing social responsiveness, repetitive behaviours, anxiety and attachment.…”