Intranasal Oxytocin Did Not Improve Social Skills in Children With Autism: A Large Trial
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- 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
- Evidence Grade:
- 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.
- Study Age:
- 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.
- Original Title:
- Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.
- Published In:
- The New England journal of medicine, 385(16), 1462-1473 (2021)
- Authors:
- Sikich, Linmarie(2), Kolevzon, Alexander(2), King, Bryan H(2), 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
- Database ID:
- RPEP-05762
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked 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.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-05762APA
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
MLA
Sikich, Linmarie, et al. "Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.." The New England journal of medicine, 2021. https://doi.org/10.1056/NEJMoa2103583
RethinkPeptides
RethinkPeptides Research Database. "Intranasal Oxytocin in Children and Adolescents with Autism ..." RPEP-05762. Retrieved from https://rethinkpeptides.com/research/sikich-2021-intranasal-oxytocin-in-children
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.