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May 15, 2002

When Are Medication Side Effects Due to the Nocebo Phenomenon?

Author Affiliations

Stephen J.LurieMD, PhD, Senior EditorIndividualAuthor

JAMA. 2002;287(19):2502-2504. doi:10.1001/jama.287.19.2502

To the Editor: I would like to add 3 clarifications to the article by Dr Barsky and colleagues on nonspecific medication side effects and the nocebo phenomenon.1 First, following the model suggested by Hahn,2 a distinction must be made between the nocebo phenomenon and placebo side effects. According to Hahn, the nocebo hypothesis proposes that expectations of sickness and the affective states associated with such expectations cause such symptoms in patients who expect them. Placebo side effects, on the other hand, occur when expectations of healing produce sickness; that is, when a positive expectation has a negative outcome. Likewise, nocebos may also have side effects; that is, when negative expectations produce positive outcomes or outcomes other than those expected. This distinction is not just a matter of semantics. I suspect that much of what is labeled as the "nocebo phenomenon" represents, in fact, placebo side effects. In patients who somaticize and in those who are diffusely pessimistic, distinguishing between the 2 concepts admittedly may be difficult. The key is that expectations play a causal role in health and healing as well as in sickness.3

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