Placebo effects in functional dyspepsia: Causes and implications for clinical trials

Abstract

Placebo responses to an apparently inactive intervention are of interest from a scientific perspective as they suggest possible mechanism(s) at work beyond the intervention itself. They are also of interest from a clinical trials perspective since high rates of placebo response limit the potential to demonstrate worthwhile efficacy of a new intervention. This mini-review was motivated by the work of Bosman and colleagues (Neurogastroenterol Motil, 2022, and e14474) that is published in this issue of the journal in which they report on a systematic review and meta-analysis of placebo response in functional dyspepsia clinical trials. The review sets the scene for their work by putting it in the context of other disorders of brain-gut interaction and extra-gastrointestinal disorders. The review canvasses potential mechanisms of placebo response.

Efficacy and safety of the herbal formula Naesohwajung-tang for functional dyspepsia: a randomized, double-blind, placebo-controlled, multi-center trial

“…Based on a systematic review of 26 RCTs aimed at determining the extent and underlying factors of the placebo response in FD, we found that the overall placebo response rate in pharmacological trials for FD was approximately 39.6% (Bosman et al, 2023). The placebo effect is thought to be influenced by psychological, neurobiological, and natural mechanisms (Jones and Holtmann, 2023). As lower baseline symptom scores are significantly related to higher placebo responses, proper entry criteria based on symptom severity should be established (Bosman et al, 2023).…”

Funktionelle Dyspepsie

“…Wenn Patienten im zeitlichen Verlauf starke Beschwerden verspüren, werden sie sich in Behandlung begeben und im weiteren Verlauf mit hoher Wahrscheinlichkeit „spontan“ eine Besserung erfahren. Entsprechend ist die „Placebo-Response“ tatsächlich nicht durch psychologische Faktoren erklärt 59 .…”

Double‐blind, randomized, 8‐week multicenter study of the efficacy and safety of STW 5‐IIversus placebo in functional dyspepsia

“…Proton pump inhibitors and histamine H2 receptor antagonists are the most commonly used evidencebased medications for FD, but the overall gain over placebo is limited. 2,9 Herbal medications have been frequently used for FD and other FGIDs for decades 10 and are acknowledged for their beneficial effects in GI complaints by the Committee on Herbal Medicinal Products of the European Medicines Agency. It has been argued that these medications should comply with regulatory standards similar to those for chemically defined therapies.…”

“…FD imposes a considerable economic burden on society 8 by repeated diagnostic testing following negative findings and a lack of effective therapies. Proton pump inhibitors and histamine H2 receptor antagonists are the most commonly used evidence‐based medications for FD, but the overall gain over placebo is limited 2,9 …”

“…Proton pump inhibitors and histamine H2 receptor antagonists are the most commonly used evidence‐based medications for FD, but the overall gain over placebo is limited. 2 , 9 …”