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  • Review Article
  • Published:

Placebo effects and their determinants in gastrointestinal disorders

Nature Reviews Gastroenterology & Hepatology volume 12, pages 472–485 (2015)Cite this article

Subjects

Key Points

  • Placebo response rates in randomized controlled trials in gastroenterology are of similar size, and mediators and moderators are of similar type to those in other medical subspecialties

  • Some trends found in other medical subspecialties—for example, an increase of the placebo response over time and high placebo responses with unbalanced randomization—have been avoided in gastroenterology

  • Experimental gastroenterology has shown that the placebo response (for example, in visceral pain and nausea) follows established rules and mechanisms (learning, expectations)

  • Brain imaging studies have demonstrated that the placebo response is not merely a response bias, but exhibits neurobiological and psychobiological properties along the gut–brain axis

  • With improved doctor–patient communication, it might be possible to boost the efficacy of drug treatment by utilizing the placebo mechanisms in daily practice

Abstract

Placebo effects in clinical trials have sparked an interest in the placebo phenomenon, both in randomized controlled trials (RCTs) and in experimental gastroenterology. RCTs have demonstrated similar short-term and long-term placebo response rates in gastrointestinal compared to other medical diagnoses. Most mediators and moderators of placebo effects in gastrointestinal diseases are also of similar type and size to other medical diagnoses and not specific for gastrointestinal diagnoses. Other characteristics such as an increase in the placebo response over time and the placebo-enhancing effects of unbalanced randomization were not seen, at least in IBS. Experimental placebo and nocebo studies underscore the 'power' of expectancies and conditioning processes in shaping gastrointestinal symptoms not only at the level of self-reports, but also within the brain and along the brain–gut axis. Brain imaging studies have redressed earlier criticism that placebo effects might merely reflect a response bias. These findings raise hope that sophisticated trials and experiments designed to boost positive expectations and minimize negative expectations could pave the way for a practical and ethically sound use of placebo knowledge in daily practice. Rather than focusing on a 'personalized' choice of drugs based on biomarkers or genes, it might be the doctor–patient communication that needs to be tailored.

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Figure 1: Placebo responses in IBS.
Figure 2: Expectancy and learning as the two best-characterized principle mechanisms that mediate placebo and nocebo effects.

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Authors and Affiliations

  1. Institute of Medical Psychology & Behavioural Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen, 45122, Germany

    Sigrid Elsenbruch

  2. Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Hospital, Tübingen University, Frondsbergstrasse 23, Tübingen, 72076, Germany

    Paul Enck

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Elsenbruch, S., Enck, P. Placebo effects and their determinants in gastrointestinal disorders. Nat Rev Gastroenterol Hepatol 12, 472–485 (2015). https://doi.org/10.1038/nrgastro.2015.117

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