Unsolved, Forgotten, and Ignored Features of the Placebo Response in Medicine.

The aim of this study was to identify topics of research that have been neglected, undervalued, or overseen in the past 2 decades of placebo/nocebo research. A highly specialized literature database containing >3200 articles on the placebo or nocebo effects or response was screened for articles covering placebo effects in nutrition, sports medicine, physical therapy, and psychotherapy; for article covering gender, age, and culture as influencing factors; for articles dealing with long-term outcome, multimodality; and for articles related to technical (eHealth, mHealth) aspects of placebo effects.

Although placebo research has gained substantial progress over the past 2 decades, it has not resolved all its puzzles, it has ignored some obvious and some less obvious facets of the placebo topic, and it has overlooked that during these years, medicine has further developed and progressed, as has the doctor-patient relationship and the social environment in which this communication happens.

The biggest threat for placebo research is that it may outdate itself by declaring all and everything as a placebo effect even if there may be better terms and concepts (eg, patient expectations, doctor-patient communication, empathy), and by ignoring that medicine continuously changes its face, for patients as well as for clinical researchers. Its biggest opportunity is the fact that it, as no other topic in medicine, requires both medical and psychological experts for its exploration and to stay updated.

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