Intranasal oxytocin does not enhance social behaviour in children, adolescents with ASD

In children and adolescents with autism spectrum disorder (ASD), intranasal oxytocin did not improve social interaction or other measures of social function related to ASD, the phase II SOARS-B* trial suggests.

“Oxytocin has been administered in clinical practice to many children with ASD,” said the researchers. However, evidence supporting its use in this setting is inconsistent, with some showing favourable results, [JAMA Psychiatry 2014;71:166-175; Proc Natl Acad Sci USA 2010;107:4389-4394; Neuropsychologia 2015;79:Pt A:53-69] while others reflecting ambiguity as to its potential to induce social function improvements. [Proc Natl Acad Sci USA 2017;114:8119-8124; Mol Psychiatry 2020;25:1849-1858]

The team evaluated 290 children and adolescents with ASD aged 3–17 years (88 percent male). Participants were randomized 1:1 to receive intranasal oxytocin or placebo, with a total target dose of 48 IUs daily. [N Engl J Med 2021;385:1462-1473]

At 24 weeks, least-squares (LS) mean changes from baseline ABC-mSW** scores were similar between oxytocin and placebo (−3.7 vs −3.5; p=0.61). This effect remained regardless whether participants communicated verbally fluently (−3.3 vs −3.7) or not (−4.1 vs −3.3).

There were also similar LS mean changes between oxytocin and placebo in terms of SRS-2-SM*** T-score (−4.5 vs −5.4), Sociability Factor score (−7.7 vs −8.3), and SB5^# Abbreviated IQ (0.9 vs 0.8).

Oxytocin was tied to higher rates of increased appetite (16 percent vs 10 percent), increased energy (10 percent vs 3 percent), and restlessness (8 percent vs 2 percent) as opposed to placebo. Nonetheless, adverse event (AE) rates were generally similar with oxytocin and placebo (82 percent vs 83 percent). Only one serious AE was deemed oxytocin-related (ie, vehicular accident owing to sedation while driving). Four oxytocin recipients discontinued the regimen mostly due to irritability or aggression.

The ability to detect improvements in children with low baseline ABC-mSW scores may have been limited, as a minimum score on this scale was not required for enrolment. However, oxytocin was no better in a subgroup of participants with a baseline ABC-mSW score of at least 11.

“In the absence of trials showing a replicable benefit of any intervention for social functioning in persons with ASD, it is difficult to know which outcome measure is most appropriate to assess potential social improvement in future trials of an intervention targeting core social deficits in ASD,” said the researchers.

An unmet need remains

“Pharmacologic interventions [for ASD] are limited to treatment of symptoms, which does not target social deficits. Although behavioural treatments have been effective in improving social and educational outcomes in some persons with ASD, there remains a need for the development of drugs that improve social functioning,” said Dr Daniel Geschwind from the David Geffen School of Medicine, University of California, Los Angeles, California, US, in a separate editorial. [N Engl J Med 2021;385:1524-1525]

While the study did not reveal social functioning benefits with oxytocin in these patients, “it may be premature to summarily reject the oxytocin signalling pathway … as a potential treatment target in ASD,” noted Geschwind.

“[S]ocial dysfunction in ASD is heterogeneous, and human social behaviour has many components. There is a need to learn more about the neurobiologic basis of complex social behaviour and to create measures that can be used effectively to evaluate its components in clinical trials,” he continued.

“Looking ahead, as we enter the era of precision medicine in which treatment may be based on genetically informed disease mechanisms, the hope is that we can leverage genetic and molecular biomarkers in trial design and patient selection to improve outcomes in ASD and other neurodevelopmental disorders,” said Geschwind.