JAMA Pediatr. 2022 Apr 1;176(4):349-356.doi: 10.1001/jamapediatrics.2021.5750.

Samuel Nurko ¹, Miguel Saps ^2 3, Joe Kossowsky ⁴, Sean Raymond Zion ^1 5, Carlo Di Lorenzo ², Karla Vaz ², Kelsey Hawthorne ¹, Rina Wu ¹, Steven Ciciora ², John Michael Rosen ⁶, Ted J Kaptchuk ⁷, John M Kelley ^7 8

Author information

¹Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, Massachusetts.

²Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, Ohio.

³Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, Florida.

⁴Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.

⁵Department of Psychology, Stanford University, Stanford, California.

⁶Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, Missouri.

⁷Program in Placebo Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

⁸Psychology Department, Endicott College, Beverly, Massachusetts.

Abstract

Importance: Although it is widely believed that concealment or deception is required to elicit a placebo response, recent studies with adults suggest that open-label placebo (OLP) (ie, honestly prescribed placebos) can yield significant benefits. No studies of OLP have been performed with children.

Objective: To evaluate the efficacy of OLP for the treatment of children and adolescents with functional abdominal pain or irritable bowel syndrome.

Design, setting, and participants: This multicenter crossover randomized clinical trial was conducted from July 1, 2015, to June 15, 2018, at 3 US centers among children and adolescents aged 8 to 18 years with functional abdominal pain or irritable bowel syndrome defined per Rome III criteria. Statistical analysis was performed from March 1, 2019, to September 30, 2020, on an intention-to-treat basis.

Interventions: Patients completed 1 week of observation prior to randomization to 1 of 2 counterbalanced groups: OLP for 3 weeks followed by a 3-week control period or control period for 3 weeks followed by OLP for 3 weeks. During the OLP period, participants took 1.5 mL of an inert liquid placebo twice a day. A standardized method for explaining the OLP was used, and the interaction with clinicians had the same duration and style for both time periods. Hyoscyamine was allowed as a rescue medication.

Main outcomes and measures: The primary outcome was the mean daily pain score during each of the interventions, measured on a 0- to 100-mm visual analog scale, where higher scores indicated greater pain. The number of rescue medications taken during each intervention served as an objective secondary measure.

Results: Thirty patients (mean [SD] age, 14.1 [3.4] years; 24 female participants [80.0%]; 16 [53.3%] with functional abdominal pain and 14 [46.7%] with irritable bowel syndrome) completed the study. The mean (SD) pain scores were significantly lower during OLP treatment compared with the control period (39.9 [18.9] vs 45.0 [14.7]; difference, 5.2; 95% CI, 0.2-10.1; P = .03). Patients took nearly twice as many hyoscyamine pills during the control period compared with during the OLP period (mean [SD] number, 3.8 [5.1] pills vs 2.0 [3.0] pills; difference, 1.8 pills; 95% CI, 0.5-3.1 pills).

Conclusions and relevance: During OLP, patients with functional abdominal pain or irritable bowel syndrome reported significantly less pain and took significantly fewer pain medications. Open-label placebo may be an effective treatment for children and adolescents with functional abdominal pain or irritable bowel syndrome.

Trial registration: ClinicalTrials.gov Identifier: NCT02389998.