The findings from the largest and longest trial of its kind call into question earlier research strongly suggesting that the drug, sometimes called the love hormone for its role in sexual activity, empathy and social bonding, would mitigate some of the problems seen in autism.
"This study makes it really clear that oxytocin doesn't work with most children, and the improvements individual families see may be due to something other than oxytocin," chief author Dr. Linmarie Sikich, an associate consulting professor at Duke University, told Reuters Health by phone.
The team quantified the severity of the symptoms using a 13-item, 40-point test where higher scores signified less social interaction.
When oxytocin was given intranasally, the least-squares mean change from baseline declined 3.7 points compared with a drop of 3.5 points among children and adolescents who used a placebo spray (P=0.61).
"These results do not support the current off-label use of oxytocin in the treatment of autism spectrum disorder," Dr. Daniel Geschwind writes in an editorial in The New England Journal of Medicine, where the study was published.
But he says the oxytocin signaling pathway should not be prematurely rejected, speculating, for example, that the hormone's effects might vary by developmental stage and "there may be critical windows for treatment effects" that were missed because the new study looked at children age 3 to 17.
Dr. Sikich said the findings were particularly surprising because a lot of animal research and small trials had shown promise.
"The underlying scientific rationale was so strong," she said. "In various animals oxytocin played a real role in how socially bonded the animals were. You had mice where you could knock out parts of the oxytocin system and get reduced social behaviors, and you could rescue it by giving oxytocin. You had other knockouts of genes associated with autism and showed social behaviors in mice that were similar to people, and that could be rescued by oxytocin."
In addition, she said, single-dose studies on humans suggested that oxytocin recipients were better at recognizing emotions or more willing to return a thrown ball to someone.
"Some of the early studies that involved six to eight weeks of treatment weren't clearly positive but there were promising signs," she said.
In the new test, patients and caregivers "were reporting positive changes. We thought we were seeing positive changes," but those turned out to be just as common in the placebo group. "This goes to the heart of why you do studies like this, so you aren't influenced by what you want to see and want to believe," said Dr. Sikich.
By the end of the study only 52% of the doctors, 49% of the primary caregivers and 50% of the children were able to correctly guess whether a child had received oxytocin or placebo.
In the test, known as SOARS-B, the children had to be off intranasal oxytocin for more than 30 days. The maximum daily allowable dose was 80 IU.
The researchers used three other scales to measure various outcomes such as social motivation, sociability, and cognitive ability.
"The three secondary outcomes essentially affirmed the absence of a difference between the trial groups," the researchers say.
Adjusting for baseline plasma oxytocin levels did not affect the findings.
"The absence of between-group differences in outcomes was similar among participants with fluent verbal communication and among those with minimal verbal communication," the researchers note.
Adverse events were seen in 82% of the children taking oxytocin versus 83% who received placebo. Severe adverse events were reported in 5% of oxytocin recipients and 7% of placebo patients.
However, the oxytocin recipients were 60% more likely to report increased appetite, three times more likely to report increased energy, four times more likely to report restlessness, twice as likely to report increased thirst and inattention, and 2.3 times more likely to say they had lost weight. The prevalence of those effects ranged from 16% to 6% in the experimental group.
In his editorial, Dr. Geschwind of the David Geffen School of Medicine at the University of California, Los Angeles, expressed concern that oxytocin had not been given in conjunction with any standardized behavioral intervention for social skills.
He equated it with trying to build muscle mass using anabolic steroids without adding rigorous physical training.
It's not clear how many children with autism are currently taking oxytocin or one of the products available on the internet that claims to contain the drug. Dr. Sikich guessed that the prevalence might be 5%.
Parents who have convinced themselves that oxytocin has helped their child "are going to devalue (the new results) and still believe that it has worked for their child. It's hard to dissuade people from that," she said. "The results are strong enough that most doctors will probably accept the findings and believe this is not a viable path to go down."
SOURCES: https://bit.ly/3mDRAPf and https://bit.ly/3Du92fP The New England Journal of Medicine, online October 13, 2021.
By Gene Emery
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