Nocebo

A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have. For example, when a patient anticipates a side effect of a medication, they can suffer that effect even if the 'medication' is actually an inert substance. The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. Both placebo and nocebo effects are presumably psychogenic, but they can induce measurable changes in the body. One article that reviewed 31 studies on nocebo effects reported a wide range of symptoms that could manifest as nocebo effects including nausea, stomach pains, itching, bloating, depression, sleep problems, loss of appetite, sexual dysfunction and severe hypotension. Mental states such as beliefs and expectations can strongly influence the outcome of disease, the experience of pain, and even success of surgery. A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have. For example, when a patient anticipates a side effect of a medication, they can suffer that effect even if the 'medication' is actually an inert substance. The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. Both placebo and nocebo effects are presumably psychogenic, but they can induce measurable changes in the body. One article that reviewed 31 studies on nocebo effects reported a wide range of symptoms that could manifest as nocebo effects including nausea, stomach pains, itching, bloating, depression, sleep problems, loss of appetite, sexual dysfunction and severe hypotension. Mental states such as beliefs and expectations can strongly influence the outcome of disease, the experience of pain, and even success of surgery. The term nocebo (Latin nocēbō, 'I shall harm', from noceō, 'I harm') was coined by Walter Kennedy in 1961 to denote the counterpart to the use of placebo (Latin placēbō, 'I shall please', from placeō, 'I please'; a substance that may produce a beneficial, healthful, pleasant, or desirable effect). Kennedy emphasized that his use of the term 'nocebo' refers strictly to a subject-centered response, a quality inherent in the patient rather than in the remedy'. That is, Kennedy rejected the use of the term for pharmacologically induced negative side effects such as the ringing in the ears caused by quinine. That is not to say that the patient's psychologically induced response may not include physiological effects. For example, an expectation of pain may induce anxiety, which in turn causes the release of cholecystokinin, which facilitates pain transmission. In the narrowest sense, a nocebo response occurs when a drug-trial subject's symptoms are worsened by the administration of an inert, sham, or dummy (simulator) treatment, called a placebo. According to current pharmacological knowledge and the current understanding of cause and effect, a placebo contains no chemical (or any other agent) that could possibly cause any of the observed worsening in the subject's symptoms. Thus, any change for the worse must be due to some subjective factor. Adverse expectations can also cause the analgesic effects of anesthetic medications to disappear. The worsening of the subject's symptoms or reduction of beneficial effects is a direct consequence of their exposure to the placebo, but those symptoms have not been chemically generated by the placebo. Because this generation of symptoms entails a complex of 'subject-internal' activities, in the strictest sense, we can never speak in terms of simulator-centered 'nocebo effects', but only in terms of subject-centered 'nocebo responses'. Although some observers attribute nocebo responses (or placebo responses) to a subject's gullibility, there is no evidence that an individual who manifests a nocebo/placebo response to one treatment will manifest a nocebo/placebo response to any other treatment; i.e., there is no fixed nocebo/placebo-responding trait or propensity. McGlashan, Evans & Orne (1969, p. 319) found no evidence of what they termed a 'placebo personality'. Also, in a carefully designed study, Lasagna, Mosteller, von Felsinger and Beecher (1954), found that there was no way that any observer could determine, by testing or by interview, which subject would manifest a placebo reaction and which would not. Experiments have shown that no relationship exists between an individual's measured hypnotic susceptibility and their manifestation of nocebo or placebo responses. It has been shown that, due to the nocebo effect, warning patients about side effects of drugs can contribute to the causation of such effects, whether the drug is real or not. This effect has been observed in clinical trials: according to a 2013 review, the dropout rate among placebo-treated patients in a meta-analysis of 41 clinical trials of Parkinson's disease treatments was 8.8%. A 2013 review found that nearly 1 out of 20 patients receiving a placebo in clinical trials for depression dropped out due to adverse events, which were believed to have been caused by the nocebo effect. A 2018 review found that half of patients taking placebos in clinical trials report intervention-related adverse events. Evidence suggests that the symptoms of electromagnetic hypersensitivity are caused by the nocebo effect. Verbal suggestion can cause hyperalgesia (increased sensitivity to pain) and allodynia (perception of a tactile stimulus as painful) as a result of the nocebo effect. Nocebo hyperalgesia is believed to involve the activation of cholecystokinin receptors. Stewart-Williams and Podd argue that using the contrasting terms 'placebo' and 'nocebo' to label inert agents that produce pleasant, health-improving, or desirable outcomes versus unpleasant, health-diminishing, or undesirable outcomes (respectively), is extremely counterproductive. For example, precisely the same inert agents can produce analgesia and hyperalgesia, the first of which, from this definition, would be a placebo, and the second a nocebo.