Effect of Open-label Placebo on Children and Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome: A Randomized Clinical Trial

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Nurko reported receiving personal fees from Innovative Health Solutions, Sucampo, and Takeda outside the submitted work. Dr Saps reported serving as an advisor for QOL Medical and Innovative Health Solutions outside the submitted work. Dr Zion reported receiving grants from the Foundation for the Science of the Therapeutic Encounter as salary support during the conduct of the study. Dr Di Lorenzo reported serving as a consultant for Takeda, Mallinckrodt, QOL Medical, Innovative Health Solutions, Mahana, and Sucampo. Dr Rosen reported receiving personal fees from Haymarket Media outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Design

Figure 2.. Study Flow and Disposition of the Patients

CBT indicates cognitive behavioral therapy.

Figure 3.. Mean Pain Scores by Treatment Condition

A, Observed patient-specific profiles (thin lines) and mean trend for each treatment group (thick lines) during the study period. B, Mean pain scores after open-label placebo or no treatment control. Errors bars indicate the standard error of the mean. aP = .03.