Cited by 298Neuroendocrine regulation and behaviorAutism Spectrum Disorder ResearchGenetics and Neurodevelopmental Disorders

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index; 16 of the 30 sources its claims cite were checked for support.

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder

Open access

Abstract

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a 24-week, placebo-controlled phase 2 trial in children and adolescents with autism spectrum disorder, daily intranasal oxytocin did not improve social withdrawal or other social/cognitive outcomes compared with placebo. Adverse-event incidence and severity were similar between groups.

Key findings

  • Primary outcome: least-squares mean change from baseline on the ABC modified Social Withdrawal subscale was −3.7 with oxytocin and −3.5 with placebo (difference, −0.2; 95% CI, −1.5 to 1.0; P=0.61).
  • Secondary outcomes generally did not differ: SRS-2 Social Motivation T-score difference 0.9 (95% CI, −1.0 to 2.9); Sociability Factor difference 0.6 (95% CI, −1.8 to 3.1); SB5 Abbreviated IQ difference 0.1 (95% CI, −2.9 to 3.0).
  • Subgroup differences were also nonsignificant: fluent verbal speech difference 0.3 (95% CI, −1.4 to 2.1); minimal verbal fluency difference −0.9 (95% CI, −2.7 to 1.0).
  • Adverse events occurred in 82% of oxytocin participants and 83% of placebo participants; one serious adverse event was considered related to oxytocin (sedation while driving leading to a motor vehicle accident at 48 IU daily).

Methods

  • Investigator-initiated, randomized, double-blind, parallel-group, placebo-controlled phase 2 trial conducted at seven academic sites from August 2014 through June 2017; participants were children and adolescents 3 to 17 years of age meeting DSM-5 criteria for autism spectrum disorder.
  • Of 355 screened, 290 were enrolled and randomly assigned 1:1, stratified by age group and verbal fluency, to intranasal oxytocin or placebo; target total daily dose was 48 IU, with flexible dosing from 8 to 80 IU over 24 weeks.
  • Primary outcome was the ABC-mSW; secondary outcomes were SRS-2-SM, Sociability Factor, and SB5 Abbreviated IQ. Efficacy used a modified intention-to-treat population (277 participants) and mixed-effect repeated-measures models; no prespecified adjustment for multiple comparisons for secondary, exploratory, or sensitivity outcomes.

Limitations

  • The paper states that the ABC-mSW has not been validated, no minimum baseline score was required for enrollment, and the flexible-dose strategy differed from previous trials.
  • The paper notes uncertainty about intranasal oxytocin absorption, brain penetration, and time course, and that the formulation differed from the Novartis Syntocinon product used in some prior trials.
  • The paper states that the 24-week treatment period might attenuate an initial early response to oxytocin; it also reports no prespecified adjustment for multiple comparisons for secondary, exploratory, or sensitivity outcomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1056/nejmoa2103583

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

16 of 30 cited sources checked · 10 supported · 0 flagged · accuracy not yet measured

Show all 18 claims

  • Probably not a substantial claim. 16
  • It may state two separate claims as one. 21
  • The quote only partly states this claim. 1
31 of 31
  • The paper relies on this without support.

    The modified ABC Social Withdrawal subscale (ABC-mSW) is a valid measure of social interaction in children and adolescents with autism spectrum disorder for the purpose of this trial.

    “The ABC-mSW that was used to determine the primary outcome was a modification of the ABC Lethargy–Social Withdrawal subscale that omitted three questions (3, 32, and 53) pertaining to reduced physical movement in order to increase specificity for social function.”
    “our primary outcome was based on the use of the ABC-mSW, which has not been validated.”
1 of 1

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Metadata

Authors
Sikich, L., Kolevzon, A., King, B. H., McDougle, C. J., Sanders, K. B., Kim, S.-J., Spanos, M., Chandrasekhar, T., Trelles, M. D. P., Rockhill, C. M., Palumbo, M. L., Witters Cundiff, A., Montgomery, A., Siper, P., Minjarez, M., Nowinski, L. A., Marler, S., Shuffrey, L. C., Alderman, C., Weissman, J., Zappone, B., Mullett, J. E., Crosson, H., Hong, N., Siecinski, S. K., Giamberardino, S. N., Luo, S., She, L., Bhapkar, M., Dean, R., Scheer, A., Johnson, J. L., Gregory, S. G., & Veenstra-VanderWeele, J.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • From the Department of Psychiatry and Behavioral Sciences (L. Sikich, M.S., T.C., C.A., A.S.), the Duke Clinical Research Institute (L. Sikich, C.A., S.L., L. She, M.B.), the Duke Molecular Physiology Institute (S.K.S., S.N.G., S.G.G.), and the Departments of Biostatistics and Bioinformatics (S.L.) and Neurology (S.G.G.), Duke University, Durham, the Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill (L. Sikich, M.S., T.C., C.A., R.D., A.S., J.L.J.), and SAS Institute, Cary (J.L.J.) — all in North Carolina; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai (A.K., M.D.P.T., P.S., J.W.), the Department of Psychiatry, Columbia University (A.M., L.C.S., N.H., J.V.-V.), and New York State Psychiatric Institute (J.V.-V.), New York, and the Center for Autism and the Developing Brain, Weill Cornell Medicine, White Plains (J.V.-V.) — all in New York; the Department of Psychiatry, University of California San Francisco, San Francisco (B.H.K.); the Department of Psy...
Venue
New England Journal of Medicine
Published
2021-10-14
Volume
385
Issue
16
Pages
1462-1473
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W3206744275
Cited by
298
References
36
Citations by year
2026: 52 · 2025: 53 · 2024: 52 · 2023: 74 · 2022: 63 · 2021: 4
FWCI
23.92
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Florida International University Digital Commons (Florida International University) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD073984)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
intranasal oxytocin, autism spectrum disorder, children and adolescents, social withdrawal, social functioning, Aberrant Behavior Checklist, adverse events, cognitive function
MeSH terms
Autism Spectrum Disorder, Administration, Intranasal, Adolescent, Child, Child, Preschool, Double-Blind Method, Female, Humans, Male, Oxytocin, Social Behavior, Least-Squares Analysis, Treatment Failure, Social Skills

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