The Placebo and Nocebo Phenomena: Their Clinical Management and Impact on Treatment Outcomes

Clin Ther. 2017 Mar;39(3):477-486. doi: 10.1016/j.clinthera.2017.01.031. Epub 2017 Feb 23.


Purpose: This overview focuses on placebo and nocebo effects in clinical trials and routine care. Our goal was to propose strategies to improve outcomes in clinical practice, maximizing placebo effects and reducing nocebo effects, as well as managing these phenomena in clinical trials.

Methods: A narrative literature search of PubMed was conducted (January 1980-September 2016). Systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on placebo or nocebo effects in clinical practice were included in the qualitative synthesis. Search terms included: placebo, nocebo, clinical, clinical trial, clinical setting, placebo effect, nocebo effect, adverse effects, and treatment outcomes. This search was augmented by a manual search of the references of the key articles and the related literature.

Findings: Placebo and nocebo effects are psychobiological events imputable to the therapeutic context. Placebo is defined as an inert substance that provokes perceived benefits, whereas the term nocebo is used when an inert substance causes perceived harm. Their major mechanisms are expectancy and classical conditioning. Placebo is used in several fields of medicine, as a diagnostic tool or to reduce drug dosage. Placebo/nocebo effects are difficult to disentangle from the natural course of illness or the actual effects of a new drug in a clinical trial. There are known strategies to enhance clinical results by manipulating expectations and conditioning.

Implications: Placebo and nocebo effects occur frequently and are clinically significant but are underrecognized in clinical practice. Physicians should be able to recognize these phenomena and master tactics on how to manage these effects to enhance the quality of clinical practice.

Keywords: adverse effects; clinical trial; nocebo; pharmacology; placebo; treatment.

Publication types

  • Review

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Nocebo Effect*
  • Placebo Effect*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome