Placebo Responses and Placebo Effects in Functional Gastrointestinal Disorders

Much has been written about the placebo effects in functional gastrointestinal disorders (FGD), especially in irritable bowel syndrome (IBS), driven by some early statements that in randomized controlled trials (RCT) of IBS, the placebo effect might be specifically high { and thus, corrupts the efficacy of novel drugs developed for this condition. We address in this review three central questions related to this: What is the size placebo effect in FGD, especially in IBS, and is it different from the placebo effect seen in other gastro-intestinal disorders? Is the placebo effect in FGD different from other functional, non-intestinal disorders, e.g. in other pain syndromes? Is the placebo effect in FGD related to placebo effects seen in psychiatry, e.g. in depression, anxiety disorders and alike? Following this discussion, we will raise a fourth question as the result of the three: What are the consequences of this for future drug trials in FGD? In summary we conclude that, contrary to common belief and discussion, the placebo effect seen in RCT in FGD is not specifically high and extraordinary, as compared to other, comparable (i.e. functional) disorders. It shares less than expected commonalities with the placebo effect in psychiatry, and very few predictors have yet been identified that determine its effect size, especially some that are driven by design features of the studies. Current practice of RCT in IBS seems to limit and control the placebo effect quite well, and future trials practice, e.g. head-to-head trial still offer options to maintain this control, even in the absence of placebos used.