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Intranasal oxytocin fails to improve social functioning of autistic children

By Eleanor McDermid, medwireNews Reporter

Intranasal oxytocin therapy did not improve the social or cognitive functioning of children and adolescents with autism in a randomised trial published in The New England Journal of Medicine.

Linmarie Sikich (Duke University, Durham, North Carolina, USA) conducted the 24-week trial – SOARS-B – to address the “equivocal results” of previous trials, which were smaller and in most cases shorter.

“Many children with autism spectrum disorder are thought to have tried intranasal oxytocin therapy on the basis of putatively promising data”, they observe.

This placebo-controlled trial included 277 participants in the modified intention-to-treat analysis – all aged 3 to 17 years (average 10.4 years, 87% boys) – with autism according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria. Oxytocin was started at a once-daily dose of 8 IU, with a target dose of 24 IU twice daily.

The median ABC modified Social Withdrawal subscale score at baseline was 11.0 points, with higher scores indicating less social interaction. After 24 weeks of treatment, children taking oxytocin had a least squares mean reduction of 3.7 points, compared with a 3.5-point reduction in the placebo group, with no significant difference between the two.

The 52% of participants who had fluent speech and were taking oxytocin had a least squares mean increase of 0.3 points, while those with minimal verbal fluency had a 0.9-point reduction, with again no significant difference between the groups.

There were three secondary outcomes, of SRS-2 Social Motivation subscale, the Sociability Factor, and SB5 Abbreviated IQ.

Changes in these measures “essentially affirmed the absence of a difference between the trial groups”, say the researchers.

The adverse event rate was similar between the treatment groups, although rates of increased appetite, energy, and restlessness; subjective weight loss; increased thirst; inattention; and myalgia were higher with oxytocin than placebo.

One serious adverse event was thought to be related to oxytocin treatment: sedation while driving, which led to an accident.

Despite the overall negative findings, the author of a linked editorial, Daniel Geschwind (University of California, Los Angeles, USA), suggests that “it may be premature to summarily reject the oxytocin signaling pathway (or efforts to increase social motivation in general) as a potential treatment target in autism spectrum disorder.”

He outlines various factors that could have contributed to the negative findings, including that “the drug was administered without concomitant standardized behavioral intervention for social skills”, giving the analogy of attempting “to build athletic prowess by the administration of anabolic steroids without simultaneous rigorous physical training.”

Geschwind therefore concludes: “Given these uncertainties and the short half-life of oxytocin, clinical efficacy may require drug administration that is temporally coupled with behavioral intervention.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2021; 385: 1462–1473

N Engl J Med 2021; 385: 1524–1525