Implications of Placebos and Nocebos in Clinical Practice

  • Dimos D. MitsikostasEmail author
Part of the Headache book series (HEAD)


The majority of unwanted adverse events and symptoms (AEs) reported by patients in randomized clinical trials (RCTs) often are not caused by the medication, because the same AEs also occur in the placebo group of the study, referring as nocebo AEs. Nocebo also occurs in clinical practice were switching from brand name to generic may also increase AEs leading to treatment discontinuation. Patients’ expectations are important determinants of nocebo, treatment outcomes, and adherence. The proportion of patients displaying nocebo behaviors in RCTs for migraine and tension-type headache (TTH) prevention has been estimated up to 43% and 24%, respectively; in addition, 5% of placebo-treated patients discontinued treatment because of AEs (nocebo dropouts) for both conditions. As someone could expect, in real life nocebo is even higher reaching 58% and 54%, respectively. On the other hand, placebo plays an essential positive role in therapeutics for all primary headache disorders, reaching up to 45% in RCTs for headaches, but there is no assay to estimate placebo in clinical practice. To improve headache outcome, physicians should limit nocebo and enhance placebo. There is evidence that nocebo effects can be minimized and even reversed by conditioning with verbal suggestion; thus doctor-patient communication and relation display substantial importance, together with other factors including age, gender, personality, previous medical experiences, media and Internet information, treatment price, treatment’s safety profile, and speed of dose titration that are fully summarized in this article.


Migraine Tension-type headache Cluster headache Nocebo Treatment Adverse events Patients’ needs Doctor-patient communication 


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.1st Neurology Department, Aeginition HospitalNational and Kapodistrian University of AthensAthensGreece

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