A Systematic Review of Factors That Contribute to Nocebo Effects

Objectives: Medication side effects are common, often leading to reduced quality of life, nonadherence, and financial costs for health services. Many side effects are the result of a psychologically mediated nocebo effect. This review identifies the risk factors involved in the development of nocebo effects. Method: Web of Science, Scopus, MEDLINE, PsycINFO, Journals@Ovid full text, and Global Health were searched using the terms nocebo and placebo effect. To be included, studies must have exposed people to an inert substance and have assessed 1 or more baseline or experimental factor(s) on its ability to predict symptom development in response to the inert exposure. Results: Eighty-nine studies were included; 70 used an experimental design and 19 used a prospective design, identifying 14 different categories of risk factor. The strongest predictors of nocebo effects were a higher perceived dose of exposure, explicit suggestions that the exposure triggers arousal or symptoms, observing people experiencing symptoms from the exposure, and higher expectations of symptoms. Conclusions: To reduce nocebo induced symptoms associated with medication or other interventions clinicians could reduce expectations of symptoms, limit suggestions of symptoms, correct unrealistic dose perceptions, and reduce exposure to people experiencing side effects. There is some evidence that we should do this especially for persons with at-risk personality types, though exactly which personality types these are requires further research. These suggestions have a downside in terms of consent and paternalism, but there is scope to develop innovative ways to reduce nocebo effects without withholding information.