Open-Label Placebo Improves Symptoms in Pediatric IBS and Functional Abdominal Pain

David Wild

February 01, 2022

A spoonful of sugar helps the medicine go down — but what if the sugar is the medicine?

Nearly 3 in 4 children with irritable bowel syndrome (IBS) or unexplained abdominal pain reported at least a 30% improvement in discomfort after taking a regimen of sugar water they knew had no medicinal properties.

The findings, published online in JAMA Pediatrics January 31, also revealed that participants used significantly less rescue medications when taking the so-called "open-label placebo." The magnitude of the effect was enough to meet one of the criteria from the US Food and Drug Administration to approve drugs to treat IBS, which affects between 10% and 15% of children in the United States.

Although open-label placebo is not ready for clinical use, IBS expert Miranda van Tilburg, PhD, said she is "glad we have evidence" of a strong response in this patient population and that the results "may make clinicians rethink how they introduce treatments.

"By emphasizing their belief that a treatment may work, clinicians can harness the placebo effect," van Tilburg, professor of medicine and vice chair of research at Marshall University, Huntington, West Virginia, told Medscape Medical News.

Study leader Samuel Nurko, MD, MPH, the director of the Functional Abdominal Pain Program at Harvard Medical School, Boston, Massachusetts, said placebo-controlled trials in patients with IBS and functional abdominal pain consistently show a "very high placebo response." The question his group set out to answer, he said, was: "Can we get the pain symptoms of these children better by giving them placebo with no deception?"

Between 2015 and 2018, Nurko and colleagues randomly assigned 30 children and adolescents, ages 8 to 18 years, with IBS or functional abdominal pain to receive either an open-label inert liquid placebo — consisting of 85% sucrose, citric acid, purified water, and the preservative methyl paraben — twice daily for 3 weeks followed by 3 weeks with no placebo, or to follow the reverse sequence. Roughly half (53%) of the children had functional abdominal pain, and 47% had IBS as defined by Rome III criteria.

Researchers at the three participating clinical sites followed a standardized protocol for explaining the nature of placebo ("like sugar pills without medication"), telling participants that adults with conditions like theirs often benefit from placebo when they receive it as part of blinded, randomized clinical trials. Participants in the study were allowed to use hyoscyamine, an anticholinergic medication, as rescue treatment during the trial.

Nurko's team reported that patients had a mean pain score of 39.9 on a 100-point visual analogue scale during the open-label placebo phase of the trial and a mean score of 45 during the control period. That difference was statistically significant (P = .03), they said.

Participants took an average of two hyoscyamine pills during the placebo phase, compared to 3.8 pills during the 3-week period when they did not receive placebo (P < .001).

Nearly three fourths (73.3%) of children in the study reported that open-label placebo improved their pain by over 30%, thus meeting one of the FDA's criteria for clinical evaluation of drugs for IBS. Half said the placebo liquid cut their pain by more than 50%.

Nurko said the findings highlight the need to address "mind-body connections" in the management of gut-brain disorders. Like van Tilburg, he cautioned that open-label placebo "is not ready for widespread use. Placebo is complicated, and we need to understand the mechanism" underlying its efficacy.

"The idea is eventually we will be able to sort out the exact mechanism and harness it for clinical practice," he added.

However, van Tilburg expressed that using placebo therapy to treat children and adolescents with these conditions could send the message that "the pain is not real or all in their heads. Children with chronic pain encounter a lot of stigma, and this kind of treatment may increase the feeling of not being believed," she said. "We should be careful to avoid this."

The study was funded by the National Institutes of Health, the Swiss National Science Foundation, the Schwartz family fund, the Foundation for the Science of the Therapeutic Relationship, and the Morgan Family Foundation.

JAMA Pediatrics. Published online January 31, 2022. Abstract

David Wild is a medical writer in Toronto.

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