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The placebo and nocebo effects in functional urology

Nature Reviews Urology volume 19, pages 171–189 (2022)Cite this article

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Abstract

A placebo is an inert substance normally used in clinical trials for comparison with an active substance. However, a placebo has been shown to have an effect on its own; commonly known as the placebo effect. A placebo is an essential component in the design of conclusive clinical trials but has itself become the focus of intense research. The placebo effect is partly the result of positive expectations of the recipient on the state of health. Conversely, a nocebo effect is when negative expectations from a substance lead to poor treatment outcomes and/or adverse events. Randomized controlled trials in functional urology have demonstrated the importance of the placebo and nocebo effects across different diseases such as overactive bladder, urinary incontinence, lower urinary tract symptoms and interstitial cystitis/painful bladder syndrome, as well as male and female sexual dysfunction. Understanding the true nature of the placebo–nocebo complex and the scope of its effect in functional urology could help urologists to maximize the positive effects of this phenomenon while minimizing its potentially negative effects.

Key points

  • Placebo and nocebo effects have major roles in functional urological ailments.

  • The mechanisms by which the placebo and nocebo effects function are not fully understood.

  • The pontine micturition centre might be affected by positive and negative expectations through a cascade of events resulting in improvement or worsening of functional urological symptoms.

  • Clinicians need to consider the placebo and nocebo phenomena when managing a patient with a functional urological ailment.

  • Clinicians should be trained regarding the placebo and nocebo effects with the aim of maximizing the benefits of the placebo effect and minimizing the harms of the nocebo effect.

  • An individualized approach and shared decision-making should be performed when dealing with placebo and nocebo effects, as each individual has different perceptions with regard to placebo and nocebo phenomena.

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Fig. 1: Methods to harness the placebo effect in daily practice based on a model by Enck and colleagues59.
Fig. 2: The placebo effect as a psychophysiological response.
Fig. 3: Understanding clinical importance.

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Authors and Affiliations

  1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Hadi Mostafaei, Sandra Jilch, Greta Lisa Carlin, Keiichiro Mori, Fahad Quhal, Benjamin Pradere, Ekaterina Laukhtina, Victor M. Schuettfort, Abdulmajeed Aydh, Reza Sari Motlagh & Shahrokh F. Shariat

  2. Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Hadi Mostafaei & Sakineh Hajebrahimi

  3. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan

    Keiichiro Mori

  4. King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia

    Fahad Quhal

  5. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia

    Ekaterina Laukhtina & Shahrokh F. Shariat

  6. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Victor M. Schuettfort

  7. King Faisal Medical City, Abha, Saudi Arabia

    Abdulmajeed Aydh

  8. Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Reza Sari Motlagh

  9. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Claus G. Roehrborn & Shahrokh F. Shariat

  10. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    Shahrokh F. Shariat

  11. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

  12. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

    Shahrokh F. Shariat

  13. Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan

    Shahrokh F. Shariat

  14. European Association of Urology research foundation, Arnhem, Netherlands

    Shahrokh F. Shariat

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Contributions

H.M., S.J. and E.L. researched data for the article. H.M., K.M., F.Q., V.M.S., A.A., C.G.R., S.F.S. and S.H. made substantial contributions to discussions of content. H.M., G.L.C. and R.S.M. wrote the article. H.M., B.P., C.G.R., S.F.S. and S.H. reviewed and edited the manuscript before submission.

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Correspondence to Shahrokh F. Shariat.

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Competing interests

S.F.S. is an advisory board member and/or speaker for Astellas, AstraZeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Jansen, Lissy, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Sanochemia, Sanofi and Wolff. C.G.R. is a consultant for GSK, Lilly, Procept, NxThera, Neotract and Sophiris and has previously received grants or research support from NxThera, Neotract, Procept and Astellas. The other authors declare no competing interests.

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Nature Reviews Urology thanks Linda Cardozo, Francisco Cruz and Gommert van Koeveringe for their contribution to the peer review of this work.

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Glossary

Regression to the mean

Regression to the mean is a statistical term that indicates that if a variable from a population is extreme in the first measure it is likely that it will move to the mean (become less extreme) in the next measure.

Natural history

The natural history of a disease is the course of a disease from the beginning to resolution.

Symptom fluctuations

Symptom fluctuations are defined as a constantly changing symptom presentation between one level or another.

Classical conditioning

Classical conditioning is a behavioural process in which an unconditioned stimulus (such as food) is paired with a conditioned stimulus (such as a bell).

Hidden conditioning

Hidden conditioning is when the process of classical conditioning proceeds without the target individual noticing.

Open conditioning

Open conditioning is when the target of conditioning is aware of the process of classical conditioning.

Anchor-based method

The anchor-based method compares changes in scores with an ‘anchor’ as a reference. An anchor establishes whether the patient is better after treatment than baseline according to the patient’s own experience.

Distribution-based method

The distribution-based approach is a method of determining minimal clinically important changes. It relies on the variability of data and the statistical characteristics of estimates of magnitudes of change.

Delphi technique

The Delphi method is a process used to reach an agreement or decision by surveying a panel of experts.

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Mostafaei, H., Jilch, S., Carlin, G.L. et al. The placebo and nocebo effects in functional urology. Nat Rev Urol 19, 171–189 (2022). https://doi.org/10.1038/s41585-021-00545-2

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