Effetto Placebo: come districarsi tra vero e falso

Author/s Luigi Alberto Pini, Antonietta Vilella
Publishing Year 2019 Issue 2019/1 Language English
Pages 16 P. 131-146 File size 1831 KB
DOI 10.3280/RSF2019-001009
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One of the main problems in the present age is the enormous amount of information we have access to in every instant involving all types of questions, without having any direct experience on the topic. Therefore, in order to make appropriate choices it is important to discriminate between fake or scientifically proven news. This problem also applies to some of the most used words in medicine: placebo and placebo effect, which are not always fully understood by health professionals. In the past years a modern interpretation of placebo and its effects has become evident. This new interpretation is also important in order to make progress in the study of placebo. This mini-review will address the meaning and the use of the placebo effect in medical practice, and will deal with the biochemical mechanisms underlying the phenomenon mainly in the field of analgesia and pain perception. In fact, the placebo and nocebo effects, even when seen as psychological or ritual aspects of the therapeutic act, may change the biochemistry and the neuronal circuitry of the brain. Moreover, the mechanisms activated by placebos and nocebo have been found to be similar and often the same as those activated by drugs, whereas research has identified many types of responses emerging from different types of placebo. Finally, ethical problems arising from the use of placebo in medicine will be mentioned.

Keywords: Placebo, nocebo, fake news, myths, scientific evidence

  1. [1] de Craen AJ, Kaptchuk, TJ, Tijssen, JG, Kleijnen J. Placebos and placebo effects in medicine: historical overview. Journal of Royal Society of Medicine 1999; 92: 511-515.
  2. [2] Price DD, Finniss DG, Benedetti F. A comprehensive review of the placebo effect: recent advances and current thought. Annual Review of Clinical Psychology 2008; 59: 565-590.
  3. [3] Amanzio M, Pollo A, Maggi G, Benedetti F. Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain 2001; 90: 205-215.
  4. [4] Beecher HK. The powerful placebo. Journal of American Medical Association 1955; 159: 1602-1606.
  5. [5] Bennett G. J. Does the word “placebo” evoke a placebo response? Pain 2018; 159: 1928-1931.
  6. [6] Benedetti F. Placebo effects: from the neurobiological paradigm to translational implications. Neuron 2014; 84: 623-637.
  7. [7] Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. Journal of Neuroscience 2003; 23: 4315-4323.
  8. [8] Ingvar M. Learning mechanisms in pain chronification-teachings from placebo research. Pain 2015; 156 Suppl 1: S18-23. [9] Montgomery GH & Kirsch I. Classical conditioning and the placebo effect. Pain 1997; 72: 107-113.
  9. [10] Benedetti F, Piedimonte A, Frisaldi E. How do placebos work? European Journal of Psychotraumatology 2018; 9: 1533370.
  10. [11] de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ. Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science 2001; 293: 1164-1166.
  11. [12] Eippert F, Finsterbusch J, Bingel U, Buchel C. Direct evidence for spinal cord involvement in placebo analgesia. Science 2009; 326: 404.
  12. [13] Amanzio M & Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. Journal of Neuroscience 1999; 19: 484-494.
  13. [14] Bendetti F, Amanzio M, Thoen W. Disruption of opioid-induced placebo responses by activation of cholecystokinin type-2 receptors. Psychopharmacology (Berl) 2011; 213(4): 791-7.
  14. [15] Benedetti F, Amanzio M, Vighetti S, Asteggiano G. The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. Journal of Neuroscience 2006; 26: 12014-12022.
  15. [16] Benedetti F, Amanzio M, Rosato R, Blanchard C. Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nature Medicine 2011a; 17: 1228-1230.
  16. [17] Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science 2004; 303: 1162-1167.
  17. [18] Keltner JR, Furst A, Fan C, Redfern R, Inglis B, Fields HL. Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. 2006; Journal of Neuroscience 26: 4437-4443.
  18. [19] Hashmi JA, Baria AT, Baliki, MN, Huang L, Schnitzer TJ et al. Brain networks predicting placebo analgesia in a clinical trial for chronic back pain. Pain 2012; 153: 2393-2402.
  19. [20] Schmidt-Wilcke T, Ichesco E, Hampson JP, Kairys A, Peltier S, Harte S, et al. Resting state connectivity correlates with drug and placebo response in fibromyalgia patients. Neuroimage: Clinical 2014; 6: 252-261.
  20. [21] Tetreault P, Mansour A, Vachon-Presseau E, Schnitzer TJ, Apkarian AV, Baliki MN. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials. PLoS Biology 2016; 14, e1002570.
  21. [22] Hoffman GA, Harrington A, Fields HL. Pain and the placebo: what we have learned. Perspectives in Biology and Medicine 2005; 48: 248-265.
  22. [23] Machado LA, Kamper SJ, Herbert RD, Maher CG, McAuley JH. Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials. Rheumatology 2009; 48: 520-527.
  23. [24] Howick J, Webster R, Kirby N, Hood K. Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Trials 2018; 19: 674.
  24. [25] Amanzio M, CorazziniLL, Vase L, Benedetti F. A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain 2009; 146: 261-269.
  25. [26] Hauser W, Bartram C, Bartram-Wunn E, Tolle T. Adverse events attributable to nocebo in randomized controlled drug trials in fibromyalgia syndrome and painful diabetic peripheral neuropathy: systematic review. The Clinical Journal of Pain 2012; 28: 437-451.
  26. [27] Mitsikostas DD, Chalarakis NG, Mantonakis LI, Delicha EM, Sfikakis, PP. Nocebo in fibromyalgia: meta-analysis o placebo-controlled clinical trials and implications for practice. European Journal of Neurology 2012; 19: 672-680.
  27. [28] Papadopoulos D & Mitsikostas DD. A meta-analytic approach to estimating nocebo effects in neuropathic pain trials. Journal of Neurology 2012; 259: 436-447.
  28. [29] Shafiq F, Mitsikostas DD, Zis P. Nocebo in motor neuron disease: systematic review and meta-analysis of placebo-controlled clinical trials. Amyotrophic Lateral Sclerosis Frontotemporal Degeneration 2017; 18: 576-582.
  29. [30] Stathis P, Smpiliris M, Konitsiotis S, Mitsikostas DD. Nocebo as a potential confounding factor in clinical trials for Parkinson’s disease treatment: a metaanalysis. European Journal of Neurology 2013; 20: 527-533.
  30. [31] Sthal SM, Greenberg GD. Placebo response rate is ruining drug development in psychiatry: why is this happening and what can we do about it? Editorial. Acta Psychiatrica Scandinavica 2019; 139: 105-107.
  31. [32] Kubo K, Fleischhacker WW, Suzuki T, Yasui-Furukori N, Mimura M, Uchida H. Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs. Acta Psychiatrica Scandinavica 2019; 139: 108-116.
  32. [33] Evers AWM, Colloca L, Blease C, Annoni M, Atlas LY, Benedetti F, et al. Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus. Psychotherapy and Psychosomatics 2018; 87: 204-210

Luigi Alberto Pini, Antonietta Vilella, Placebo effect between evidence and myths: How to distinguish true from fake news in "RIVISTA SPERIMENTALE DI FRENIATRIA" 1/2019, pp 131-146, DOI: 10.3280/RSF2019-001009