Summary: Oxytocin therapy is ineffective at improving social skills in children on the autism spectrum.
Source: Duke University
Oxytocin, a naturally occurring hormone that acts as a chemical messenger in the brain, showed no evidence of helping children with autism gain social skills, according to a large national study appearing Oct. 13 in the New England Journal of Medicine.
While disappointing for those holding hope that oxytocin could benefit children with autism, the long-awaited finding provides clarity for a drug that has shown mixed outcomes in smaller, less robust studies.
“There was a great deal of hope this drug would be effective,” said the study’s principal investigator and lead author, Linmarie Sikich, M.D., associate consulting professor in the Department of Psychiatry & Behavioral Sciences at Duke University School of Medicine. “All of us on the study team were hugely disappointed, but oxytocin does not appear to change social function of people with autism.”
Oxytocin is typically used to induce labor, but because of its activity in the brain, it has been investigated as a treatment for autism. Evidence has been conflicting, with several smaller studies suggesting it improved social and cognitive function among some children with autism, while other studies showed no benefit.
Sikich and colleagues, including senior author Jeremy Veenstra-VanderWeele, M.D., of New York State Psychiatric Institute and Columbia University, designed the multi-site trial to provide the best evidence yet about whether oxytocin was a safe and effective treatment for children with Autism Spectrum Disorder.
The research team enrolled 290 children ages 3-17, stratified by age and the severity of their autism symptoms. The children were randomized in similar, equal-sized groups to receive oxytocin or a placebo via a daily nasal spray over 24 weeks.
The study aimed to see if the regimen of oxytocin would have a measurable impact on the children’s social abilities based on screenings and assessments at the start of the trial, midway through and at the end. Both researchers and the children’s parents provided assessments using standard analytic tools for autism.
While the oxytocin was well tolerated and had few side effects, it showed no significant benefit among the group of children who received it compared to those who received the placebo.
“Thousands of children with autism spectrum disorder were prescribed intranasal oxytocin before it was adequately tested,” Veenstra-VanderWeele said. “Thankfully, our data show that it is safe. Unfortunately, it is no better than placebo when used daily for months. These results indicate that clinicians and families should insist that there is strong evidence for the safety and benefit of new treatments before they are provided to patients in the clinic.”
Sikich said no further study is likely of oxytocin, given the negative findings: “Our consensus as investigators is that there is no evidence in this large study that is strong enough to justify more investigation of oxytocin as a treatment for autism spectrum disorders.”
In addition to Sikich and Veenstra-VanderWeele, study authors include Alexander Kolevzon, Bryan H. King, Christopher J. McDougle, Kevin B. Sanders, Soo-Jeong Kim, Marina Spanos, Tara Chandrasekhar, Pilar Trelles, Carol M. Rockhill, Michelle L. Palumbo, Allyson Witters Cundiff, Alicia Montgomery, Paige Siper, Mendy Minjarez, Lisa A. Nowinski, Sarah Marler, Lauren C. Shuffrey, Cheryl Alderman, Jordana Weissman, Brooke Zappone, Jennifer E. Mullett, Hope Crosson, Natalie Hong, Stephen K. Siecinski, Stephanie N. Giamberardino, Sheng Luo, Lilin She, Manjushri Bhapkar, Russell Dean and Abby Scheer.
Funding: The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD073984) and the National Center for Advancing Translational Sciences (UL1TR002489).
Original Research: Closed access. “Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder” by Linmarie Sikich, M.D., Alexander Kolevzon, M.D., Bryan H. King, M.D., Christopher J. McDougle, M.D., Kevin B. Sanders, M.D., Soo-Jeong Kim, M.D., Marina Spanos, Ph.D., Tara Chandrasekhar, M.D., M.D. Pilar Trelles, M.D., Carol M. Rockhill, M.D., Michelle L. Palumbo, M.D., Allyson Witters Cundiff, M.D., Alicia Montgomery, M.B., B.S., Paige Siper, Ph.D., Mendy Minjarez, Ph.D., Lisa A. Nowinski, Ph.D., Sarah Marler, M.A., Lauren C. Shuffrey, Ph.D., Cheryl Alderman, B.S., Jordana Weissman, B.A., Brooke Zappone, B.S., Jennifer E. Mullett, R.N., Hope Crosson, B.S.W., Natalie Hong, M.S., Stephen K. Siecinski, B.S., Stephanie N. Giamberardino, Sc.M., Sheng Luo, Ph.D., Lilin She, Ph.D., Manjushri Bhapkar, M.S., Russell Dean, M.S., Abby Scheer, M.S.I.S., Jacqueline L. Johnson, Dr.P.H., Simon G. Gregory, Ph.D., and Jeremy Veenstra-VanderWeele, M.D.. NEJM
Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder
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.
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.
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.
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.