Farmacoriflessioni
Il placebo, 23 anni dopo
PLACEBO
FRANCO PANIZON1, MASSIMO FONTANA2
1Professore Emerito, Dipartimento di Scienze della Riproduzione e dello Sviluppo, Università di Trieste
2Struttura Complessa di Pediatria, Ospedale dei Bambini “V. Buzzi”, Milano
Novembre 2008 - pagg. 571 -577
Abstract
The meaning itself of the word placebo has changed in time: from “drug prescribed to relieve the mind rather than because of its actual effect on the disease” to “improvement observed after the simulated treatment” or to “there is not only one placebo effect but there are many”. However, the “measurable” placebo effect remains a debatable and modest
phenomenon. A systematic research of the trials in which patients were administered “placebo” or “no treatment” shows a doubtful result, which is very variable in the different contexts and in the different diseases and which has certain significance only for the effect on pain. Anyhow, the studies of functional neuroimaging show that something happens in the patients treated with placebo. The most consistent observations are those collected on
pain, depression and Parkinson’s disease; especially the latter ones highlight protracted clinical effect, accompanied by repeated biological effects at least on two different systems (mesolimbic and striated). The observations on pain underline the activation of the antinocicettive system; it is a “natural” activation reinforced by placebo. The efficacy, repeatedly
proven, of breastfeeding or of the administration of sugar to the newborn or suckling child who undergoes a painful procedure is to be referred to this effect. As placebo effect exists, also nocebo effect does; it is due to the wait of a frightening event (undesired effect
of a drug). More generally it is possible to say that the context (stress, or vice-versa emotional
support), not necessarily mediated by the physician, has significant effects in the evolution of the disease, both in acute phases (major morbidity under stress) and in the chronic diseases (accomplishment and efficacy of the locus of control).
Suggerite dall'AI
Bibliografia
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2. Hròbjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trial comparing placebo with no treatment. N Engl J Med 2001;344: 1594-602.
3. Lewis D. A Meta-analysis in the placebo rates of remission and response trial of active ulcerative colitis. Gastroenterology 2007;132: 516-26.
4. Ramos JMJ. Efecto placebo y dolor. Bases cerebrales. Neurologia 2007;22:109-205.
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7. Benedetti F, Mayberg HS, Wager TD, Stohòer CS, Zubieta JK. Neurobiological mechanism of the placebo effect. J Neurosci 2005;25:10390-402.
8. Zubieta JK, Bueller JA, Jackson LR. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 2005; 25:7754-62.
9. Wager TD, Rilling JK, Smith EE, et al. Placebo- induced changes in FMRI in the anticipation and experience of pain. Science 2004; 303:1162-7.
10. Price DD, Milling LS, Kirsch I. An analysis of factors that contribute to the magnitudo of placebo analgesia in an experimental paradigma. Pain 1999;83:147-56.
11. Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D. The placebo response in Parkinson Study Group. Clin Neuropharmacol 1999;22:207-12.
12. Freeman TB, Vawter DE, Leaverton PE, et al. Use of placebo surgery in controlled trial of a cellular trial of a cellular-based therapy for Parkinson’s disease. N Engl J Med 1999;341: 988-92.
13. Walsh BT, Seidman SN, Sysko R, Gould M. Placebo response in studies of major depression. Variable, substantial, and growing. JAMA 2002;287:1840-87.
14. Mayberg HS, Silva SA, Brannan SK. The functional neuroanatomy of the placebo effect. Am J Psychiatry 2002;159:728-37
15. Kirsch I, Sapierstein G. Listening to prozac but hearing placebo: a meta-analysis of antidepressive medications. Prev Treat 1990;1: 2a1.
16. Mayberg HS, Brannan SK, Tekell JL, et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 2000;48:830-43.
17. Leuchter AF, Cook IA, Whitte EA, Morgan M, Abrams M. Changes in brain functions of depressed subjects during treatment with placebo. Am J Psychiatry 2002;159:122-9.
18. Petrovic P, Kalso E, Petersson KM, Ingvar M. Placebo and opioid analgesia - imaging a shared neuronal network. Science 2002;295: 1737-40.
19. Benedetti F, Arduino C, Amanzio M. Somatotropic activation of opioid system by target- directed expectation of analgesia. J Neurosci 1999;56:309-22.
20. Lidstone SC, de la Fuente-Fernandez R, Stoessl AJ. The placebo response as a reward mechanism. Semin Pain Med 2005;4:37-42.
21. Hahn RA. The nocebo phenomenon: concept, evidence, and implications for public health. Prev Med 1997;26:607-11.
22. Barsky AJ, Saintfort R, Rogers MP, Borus JF. Non specific medication side effects and the nocebo phenomenon. JAMA 2002;287: 622-7.
23. Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. N Engl J Med 1991;325:606-12.
24. Joyce C. Consistent differences in individual reaction to drug and dummies. Br J Pharmacol 1959;14:512-21.
25. Tangrea JA, Adrianza ME, Helsel WE. Risk factors for the development of placebo adverse reactions in a multicenter clinical trial. Ann Epidemiol 1994;4:327-31.
26. Strohle A. Increased response to a putative psicogenic nocebo administration in female patients with panic disorders. J Psychiatr Res 2000;34:439-442.
27. Benedetti F, Amanzio M, Casadio C. Blockade of nocebo hyperalgesia by the colecystockinin antagonist proglumide. Pain 1997;71:135-40.
28. Spriet A, Spriet C, Larousse D, Chigot M, Simon C. Methodology and results of a survey of adverse reactions to a drug in private practice. Eur J Clin Pharmacol 1977;11:181-92.
29. Schroeder K, Fahey K. Should we advise parents to administer over the counter cough medicines for acute cough? Systematic review of randomised controlled trial. Arch Dis Child 2002;86:170-5.
2. Hròbjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trial comparing placebo with no treatment. N Engl J Med 2001;344: 1594-602.
3. Lewis D. A Meta-analysis in the placebo rates of remission and response trial of active ulcerative colitis. Gastroenterology 2007;132: 516-26.
4. Ramos JMJ. Efecto placebo y dolor. Bases cerebrales. Neurologia 2007;22:109-205.
5. Lidstone SC, Stoessl AJ. Understanding the placebo effect. Contribution from neuroimaging. Mol Imaging Biol 2007;9:176-85.
6. Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet 1978; 2:654-7.
7. Benedetti F, Mayberg HS, Wager TD, Stohòer CS, Zubieta JK. Neurobiological mechanism of the placebo effect. J Neurosci 2005;25:10390-402.
8. Zubieta JK, Bueller JA, Jackson LR. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 2005; 25:7754-62.
9. Wager TD, Rilling JK, Smith EE, et al. Placebo- induced changes in FMRI in the anticipation and experience of pain. Science 2004; 303:1162-7.
10. Price DD, Milling LS, Kirsch I. An analysis of factors that contribute to the magnitudo of placebo analgesia in an experimental paradigma. Pain 1999;83:147-56.
11. Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D. The placebo response in Parkinson Study Group. Clin Neuropharmacol 1999;22:207-12.
12. Freeman TB, Vawter DE, Leaverton PE, et al. Use of placebo surgery in controlled trial of a cellular trial of a cellular-based therapy for Parkinson’s disease. N Engl J Med 1999;341: 988-92.
13. Walsh BT, Seidman SN, Sysko R, Gould M. Placebo response in studies of major depression. Variable, substantial, and growing. JAMA 2002;287:1840-87.
14. Mayberg HS, Silva SA, Brannan SK. The functional neuroanatomy of the placebo effect. Am J Psychiatry 2002;159:728-37
15. Kirsch I, Sapierstein G. Listening to prozac but hearing placebo: a meta-analysis of antidepressive medications. Prev Treat 1990;1: 2a1.
16. Mayberg HS, Brannan SK, Tekell JL, et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 2000;48:830-43.
17. Leuchter AF, Cook IA, Whitte EA, Morgan M, Abrams M. Changes in brain functions of depressed subjects during treatment with placebo. Am J Psychiatry 2002;159:122-9.
18. Petrovic P, Kalso E, Petersson KM, Ingvar M. Placebo and opioid analgesia - imaging a shared neuronal network. Science 2002;295: 1737-40.
19. Benedetti F, Arduino C, Amanzio M. Somatotropic activation of opioid system by target- directed expectation of analgesia. J Neurosci 1999;56:309-22.
20. Lidstone SC, de la Fuente-Fernandez R, Stoessl AJ. The placebo response as a reward mechanism. Semin Pain Med 2005;4:37-42.
21. Hahn RA. The nocebo phenomenon: concept, evidence, and implications for public health. Prev Med 1997;26:607-11.
22. Barsky AJ, Saintfort R, Rogers MP, Borus JF. Non specific medication side effects and the nocebo phenomenon. JAMA 2002;287: 622-7.
23. Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. N Engl J Med 1991;325:606-12.
24. Joyce C. Consistent differences in individual reaction to drug and dummies. Br J Pharmacol 1959;14:512-21.
25. Tangrea JA, Adrianza ME, Helsel WE. Risk factors for the development of placebo adverse reactions in a multicenter clinical trial. Ann Epidemiol 1994;4:327-31.
26. Strohle A. Increased response to a putative psicogenic nocebo administration in female patients with panic disorders. J Psychiatr Res 2000;34:439-442.
27. Benedetti F, Amanzio M, Casadio C. Blockade of nocebo hyperalgesia by the colecystockinin antagonist proglumide. Pain 1997;71:135-40.
28. Spriet A, Spriet C, Larousse D, Chigot M, Simon C. Methodology and results of a survey of adverse reactions to a drug in private practice. Eur J Clin Pharmacol 1977;11:181-92.
29. Schroeder K, Fahey K. Should we advise parents to administer over the counter cough medicines for acute cough? Systematic review of randomised controlled trial. Arch Dis Child 2002;86:170-5.
Corrispondenza: f.panizon@libero.it