Intranasal Oxytocin Did Not Improve Social Skills in Children With Autism: A Large Trial | Research

The takeaway

A rigorous 24-week trial of intranasal oxytocin in 290 children with autism found no improvement in social withdrawal, social functioning, or cognition compared to placebo.

p = 0.61
No significant difference between oxytocin and placebo on the primary measure of social withdrawal after 24 weeks of treatment in 290 children with autism

What the researchers found

Intranasal oxytocin (48 IU daily for 24 weeks) showed no significant improvement in social withdrawal (ABC-mSW: -3.7 vs -3.5 placebo, p=0.61) or secondary outcomes in 290 children with autism.

Why it matters

Oxytocin has been widely hyped and even prescribed off-label for autism despite limited evidence. This large, well-designed trial shows it does not work for this purpose, which should change clinical practice.

The numbers in context

290 enrolled; 146 oxytocin, 144 placebo; 24 weeks; 48 IU daily; ABC-mSW: -3.7 vs -3.5 (p=0.61); no secondary differences; similar adverse events

How the study worked

Phase 2, double-blind, placebo-controlled, randomized trial. 290 children and adolescents (3-17 years) with ASD. 1:1 randomization stratified by age and verbal fluency. 48 IU intranasal oxytocin or placebo daily for 24 weeks. Primary: ABC-mSW. Secondary: social function and IQ measures.

Who was studied

Children and adolescents aged 3-17 with autism spectrum disorder, stratified by age and verbal fluency

What this study cannot tell us

Single dose level tested (48 IU). Some patients may respond to different doses or have subtypes of autism more responsive to oxytocin. 24 weeks may not capture very long-term effects. Both groups improved, suggesting strong placebo effects.

How to read the evidence

This is a large, well-designed phase 2 randomized controlled trial published in the New England Journal of Medicine — among the highest levels of clinical evidence. The negative result is as definitive as a single trial can be.

When this study was published

Published in 2021 in the NEJM. This is the largest and most definitive trial on oxytocin for autism to date, and its negative findings have significantly dampened enthusiasm for this treatment approach.

The bigger picture

This trial is considered a definitive negative result for oxytocin as an autism treatment. Despite years of hype from smaller studies and widespread off-label prescribing, the largest and most rigorous trial to date showed no benefit. It highlights a recurring problem in neuroscience: small, poorly controlled studies generate excitement that evaporates when proper trials are conducted. The result should discourage continued off-label oxytocin prescribing for autism.

Questions still open

Could specific subgroups of children with autism (e.g., those with naturally lower oxytocin levels) still benefit from oxytocin treatment?
Did the strong placebo effect in both groups mask a small oxytocin benefit, or does oxytocin truly have no effect on autism social symptoms?
Should doctors who have been prescribing oxytocin off-label for autism stop based on this evidence?

Common questions

Does oxytocin help children with autism?

According to this large, rigorous trial — no. Despite promising results from smaller studies, 24 weeks of daily intranasal oxytocin at 48 IU showed no improvement in social behavior, social skills, or IQ compared to placebo in 290 children with autism spectrum disorder.

Should parents stop giving their autistic child oxytocin nasal spray?

This trial provides strong evidence that intranasal oxytocin does not improve social symptoms in children with autism. Parents should discuss the findings with their child's doctor. While the treatment appeared safe with similar side effects to placebo, there's no evidence it provides benefit.

Read the original research

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

The New England journal of medicine, 385(16), 1462-1473

View on PubMed ↗Publisher’s paper ↗

Citation

Sikich, Linmarie; Kolevzon, Alexander; King, Bryan H; McDougle, Christopher J; Sanders, Kevin B; Kim, Soo-Jeong; Spanos, Marina; Chandrasekhar, Tara; Trelles, M D Pilar; Rockhill, Carol M; Palumbo, Michelle L; Witters Cundiff, Allyson; Montgomery, Alicia; Siper, Paige; Minjarez, Mendy; Nowinski, Lisa A; Marler, Sarah; Shuffrey, Lauren C; Alderman, Cheryl; Weissman, Jordana; Zappone, Brooke; Mullett, Jennifer E; Crosson, Hope; Hong, Natalie; Siecinski, Stephen K; Giamberardino, Stephanie N; Luo, Sheng; She, Lilin; Bhapkar, Manjushri; Dean, Russell; Scheer, Abby; Johnson, Jacqueline L; Gregory, Simon G; Veenstra-VanderWeele, Jeremy. (2021). Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.. The New England journal of medicine, 385(16), 1462-1473. https://doi.org/10.1056/NEJMoa2103583