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Mechanisms of the placebo effect in pain and psychiatric disorders

Abstract

Placebo effect research over the past 15 years has improved our understanding of how placebo treatments reduce patient symptoms. The expectation of symptom improvement is the primary factor underlying the placebo effect. Such expectations are shaped by past experiences, contextual cues and biological traits, which ultimately modulate one’s degree of response to a placebo. The body of evidence that describes the physiology of the placebo effect has been derived from mechanistic studies primarily restricted to the setting of pain. Imaging findings support the role of endogenous opioid and dopaminergic networks in placebo analgesia in both healthy patients as well as patients with painful medical conditions. In patients with psychiatric illnesses such as anxiety disorders or depression, a vast overlap in neurological changes is observed in drug responders and placebo responders supporting the role of serotonergic networks in placebo response. Molecular techniques have been relatively underutilized in understanding the placebo effect until recently. We present an overview of the placebo responder phenotypes and genetic markers that have been associated with the placebo effect in pain, schizophrenia, anxiety disorders and depression.

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Acknowledgements

R.D.H. is supported by a CREMS Award 2013. A.K.T. is supported by the NARSAD 2010. Young Investigator Award. A.K.T. and J.L.K. are supported by the Ministry of Research and Innovation, Government of Ontario; and Genome Canada.

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Correspondence to J L Kennedy.

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R.D.H and A.K.T have no conflicts of interest to declare. J.L.K. has been a consultant to GSK, Sanofi-Aventis and Dainippon-Sumitomo and received honoraria from Eli Lilly.

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Holmes, R., Tiwari, A. & Kennedy, J. Mechanisms of the placebo effect in pain and psychiatric disorders. Pharmacogenomics J 16, 491–500 (2016). https://doi.org/10.1038/tpj.2016.15

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