The placebo and nocebo effects in cancer treatment

Abstract

In the field of cancer research both placebo and nocebo effects are observed. Thereby, not only the application of an inert substance or procedure, the placebo, but the whole therapeutic context in which a treatment is given has the potential to cause placebo and nocebo effects. Two central mechanisms are hypothesized to play important roles in their development and maintenance: expectations and conditioning. Psycho-(neuro-)biological underpinnings that correlate with placebo and nocebo effects are called placebo and nocebo responses, and support the existence of the true placebo and nocebo effects. Individual patients treated with placebos in randomized controlled trials report improvements in various cancer-related symptoms like fatigue, nausea, pain, or vasomotor symptoms. Improvement on an average group level in placebo arms could be shown for cancer-related pain, but not for weight gain or performance status. No significant placebo-induced improvements in tumor response have been shown so far. Besides desirable changes, patients in the placebo arms also report adverse events. As these unspecific side effects tend to mimic the side effect profiles of the active treatment, a priori expectations about potential side effects are thought to be relevant. Expectation and conditioning as well as their interactions are important pathways for placebo and nocebo effects. For example, the development of nausea related to chemotherapy can be seen as a result of expectations, conditioning, and their interacting processes. However, until today systematic evaluations of placebo and nocebo effects in cancer trials remain rare and especially methodologically sound integrations of effects are needed. With regard to ethical issues, demonstration of placebo and nocebo effects in cancer treatment outcome highlights considerations for enhancing placebo while decreasing nocebo effects to improve the patients' care.