Underappreciated power. Placebo and nocebo in medicine

Abstract

The term placebo is defined as a substance with no therapeutic effect that improves health by convincing the patient that the substance is effective. The term comes from the Latin “placere”, meaning “I will delight” or “do good”. Placebo is a universal tool for evaluating non-medical effects in randomized controlled trials to determine the true pharmacological effect of a drug. Examples of placebo action can be found in any field of medicine, but there is no conceptual basis that integrates it into everyday clinical practice, nor is there a corresponding medical education programme. Three main mechanisms of placebo effect are considered: the expectation model, reflective causality and the neurotransmitter model; it is necessary to take into account that these hypotheses may complement each other.Nocebo is defined as a substance that has no therapeutic effect, but worsens the condition of the person receiving it because of the negative beliefs and expectations of the person. Nocebo effect, according to several studies, can be modulated by cholecystokinin. There is evidence that cholecystokininin induces hyperalgesia, “turning” anxiety into pain. According to the negative expectation model, nocebo induces hypothalamic-pituitary-adrenal axis, which increases plasma concentrations of adrenocorticotropic hormone and cortisol. Interest in nocebo has increased in recent years due to the introduction of immunobiological biosimilars in clinical practice. There are reports of a higher frequency of drug withdrawal by patients switching from original drugs to biosimilars in open trials compared to blind ones, suggesting a nocebo effect. The conceptual basis of personalized psychopharmacotherapy is to maximize placebo effect and minimize nocebo effect in order to improve treatment outcomes.

Keywords

• placebo
• nocebo
• history
• treatment
• research