Effects of Daily Intranasal Oxytocin in Patients With Autism Spectrum Disorder

Intranasal medication
Intranasal medication
Researchers conducted a 24-week phase 2 trial of intranasal oxytocin therapy in pediatric patients with autism spectrum disorder to divulge whether it would improve social functioning.

Daily intranasal oxytocin did not significantly improve social functioning in children or adolescents with autism spectrum disorder, according to results of a phase 2 trial published in The New England Journal of Medicine.

Individuals from 7 academic sites participated in the randomized, double-blind, parallel-group, placebo-controlled trial. They received intranasal oxytocin or matching placebo, beginning at 8 IU each morning with a target total daily dose of 48 IU. After maintaining the 48 IU daily dose for 7 weeks, patients could increase the dose by 16 IU every 4 weeks, up to 80 IU. Reductions by 8 to 16 IU or maintenance at the same dose were acceptable. Reductions were required if participants had moderate or severe worsening symptoms or if they had 2 consecutive Clinical Global Impressions Improvement Scores that indicated their functioning was declining.

Participants were evaluated at baseline and at follow-up visits every 4 weeks for 24 weeks to track adverse events, concomitant treatments, and assess symptoms.

The 290 patients eligible for the study received at least 1 dose of oxytocin or placebo and were included in safety analysis. Thirteen participants had either no Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW) assessment or baseline ABC-mSW score, prompting 277 participants for the modified intention-to-treat analysis, 27 of whom were lost to follow-up before week 24. There were 114 participants in the oxytocin group and 107 in the placebo group who completed the trial.

Median ABC-mSW baseline score was 11 points for the efficacy analysis participants (87% boys). Oxytocin group individuals had mean maximal total daily dose of 67.6±16.9 IU.

Least-squares mean change from baseline to 24 weeks in ABC-mSW score was not significant (-3.7 in the oxytocin group, -3.5 in the placebo group). Between-group differences were 0.3 for participants with fluent verbal speech and -0.9 for participants with minimal verbal fluency.

There were no significant differences in ABC Lethargy-Social Withdrawal subscale or point estimate of the least-squares mean change from baseline for the Social Responsiveness Scale second edition Social Motivation subscale (SRS-2-SM), Sociability Factor score, or Stanford-Binet Intelligence Scales fifth edition (SB5) Abbreviated IQ.

The researchers reported 3 serious adverse events, including sedation in 1 individual taking 48 IU daily who was driving and had a motor vehicle accident. Four individuals in the oxytocin group discontinued due to adverse events, typically related to irritability or aggression, the researchers said. About four-fifths of individuals in each of the 2 groups experienced adverse events. Individuals in the oxytocin group were more likely to experience increased appetite, energy, restlessness, subjective weight loss, thirst, inattention, and myalgia. Mean weight gain in each group was about 2 kg.

Limitations of the study include that the ABC-mSW has not been validated and there was no minimum score required for enrollment.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Sikich L, Kolevzon A, King BH, et al. Intranasal oxytocin in children andadolescents with Autism Spectrum Disorder. N Engl J Med. 2021;385(16):1462-1473. doi: 10.1056/NEJMoa2103583