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.