Open-Label Placebo in Children With Abdominal Pain or IBS

Abstract

Source: Nurko S, Saps M, Kossovsky J, et al. Effect of Open-label placebo on children and adolescents with functional abdominal pain or irritable bowel syndrome: a randomized clinical trial [published online ahead of print January 31, 2022]. JAMA Pediatr. doi:10.1001/jamapediatrics.2021.5750Investigators from multiple institutions conducted a prospective crossover randomized trial to assess the effectiveness of open label placebo (OLP), ie, honestly prescribed placebo, in reducing pain in youths with functional abdominal pain or irritable bowel syndrome (IBS). Study participants were children 8-18 years old, with either functional abdominal pain or IBS, defined by Rome III criteria, who were enrolled at 3 children’s hospitals in the US between 2015 and 2018. During a 7-day observation period, study patients assessed their pain daily using a 0 to 100 mm visual analogue scale. Following the observation period, those with a mean daily pain scale of 25 mm were randomized to either OLP for 3 weeks or the control period. After 3 weeks, each participant crossed over to the other treatment group. A standard script was used during clinical encounters, with an explanation of placebos provided when a study child began OLP treatment. OLP was an inert suspension containing 85% sucrose, citric acid, water, and methyl paraben as a preservative, and patients were instructed to take 1.5 mL twice daily. Participants were allowed to take hyoscyamine dissolvable tablets as needed as a rescue pain medication. During the 6-week treatment period, study children recorded their daily pain using the visual analogue scale, which was the primary outcome. Differences in mean daily pain scores when participants were taking OLP or in the control period were compared using repeated-measures analysis of covariance; the model included mean pain score during the observation period and accounted for order of treatment. The main secondary outcome was number of hyoscyamine tablets used, with use during the OLP or control periods compared with a t-test.Data were analyzed on 30 patients, including 16 (53.3%) with functional abdominal pain and 14 (46.7%) with IBS. The mean age of study participants was 14.1 ±3.4 years, and 80% were female; the mean daily pain score in these youths during the 7-day observation period was 45.8 ±2.8 mm. Mean daily pain scores in study participants were 39.9 ±18.9 mm during the OLP period and 45.0 ±14.7 mm during the control period (difference, 5.2 mm; 95% CI, 0.2, 10.1; P = 0.03). Overall, 21 (70%) patients had higher daily pain scores during the control period than during the OLP period. Participants also took significantly more hysocyamine tablets during the control period than while receiving OLP (mean, 3.8 ±5.1 and 2.0 ±3.0 tablets, respectively; P = 0.001).The authors conclude that youths with functional abdominal pain or IBS experienced less pain during the OLP period than during the control period.Dr Rosenthal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Disorders of gut-brain interaction such as functional abdominal pain and IBS often are chronic and difficult to treat due to a lack of identified organic targets.1 These disorders often are characterized by disabling symptoms, a poor quality of life, and high use of health care resources.2 In several double-blind studies of medications in children with these disorders, a high rate of favorable response among those receiving placebo has been observed.3 Due to ethical concerns about patient deception, the use of deceptive placebos as only treatments largely has been discouraged. However, recent data in adults suggest that use of OLP can achieve positive results.4In the current study, the authors utilizing OLP were able to significantly reduce pain in children and adolescents with disorders of gut-brain interaction as well as decrease their use of rescue medication. They concluded that OLP may provide an ethical way to harness the placebo effect as a therapeutic tool in the clinic. This is the first study in children that confirms the findings in adults suggesting that OLP can be used without compromising the therapeutic effect.There were several limitations to the current study; these included bias with a lack of treatment blinding, non-conscious expectations (the children’s desire to please the researchers), and the crossover design potentially contributing to carryover effects since the study lacked a washout period in which no “active treatment” was being used, and a short follow-up period.How can the current study results be explained? The exact nature of the response is still not known, but understanding the process and the mechanism behind the positive response may allow its use in routine clinical care in the future. Importantly, a non-pharmacologic therapy shows promise in treating functional abdominal pain and IBS.An OLP may reduce pain in children and adolescents with functional abdominal pain and IBS. (See AAP Grand Rounds. 2017[4]:43.)5