Placebo: a brief updated review.

Alfredo Jose Pardo-Cabello, Victoria Manzano-Gamero, Emilio Puche-Cañas
Author Information
  1. Alfredo Jose Pardo-Cabello: Department of Internal Medicine, Hospital Universitario San Cecilio, Avda. de La Innovación, s/n, 18016, Granada, Spain. alfredoj.pardo.sspa@juntadeandalucia.es.
  2. Victoria Manzano-Gamero: Department of Internal Medicine, Hospital Universitario Virgen de Las Nieves, Granada, Spain.
  3. Emilio Puche-Cañas: Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain.

Abstract

Our aims were to provide updated information on placebo/nocebo effect and the potential use of placebo in clinical practice. This article can only provide a rough overview on the placebo and nocebo effect and is intended to serve as a starting point for the reader to go deeper into the corresponding literature. The placebo effect has been observed in multiple medical conditions, after oral administration, with manual therapies as well as with surgery and invasive procedures. The use of placebo in clinical trials is fundamental, although the ethics of its use is under discussion. The placebo may behave like a drug from the pharmacokinetic and pharmacodynamic point of view and can also be associated with adverse events (nocebo effect). Placebo can modify treatment by increasing or decreasing the effects of drugs. The factors associated with the occurrence of placebo effect are multiple, but in addition to those that depend on the placebo itself, the doctor-patient relationship would be the most important. As a result of findings that were published in the last two decades, the psycho-neurobiological basis of placebo is becoming better understood, although further studies are needed. In conclusion, the placebo effect in the clinic exhibits weak to moderate intensity. Placebo, in addition to its use in the clinical trial, should be considered another therapeutic remedy either as stand alone or in association with treatment, and could be useful in certain circumstances. The use of placebo should be regulated by the European health authorities through a guide in clinical practice that will improve patient care.

Keywords

References

  1. Int Rev Neurobiol. 2018;138:1-15 [PMID: 29681320]
  2. Int Rev Neurobiol. 2018;138:137-160 [PMID: 29681322]
  3. Clin Res Cardiol. 2014 Mar;103(3):229-35 [PMID: 24264475]
  4. J Epidemiol Community Health. 2022 Apr;76(4):335-340 [PMID: 34625519]
  5. J Clin Psychopharmacol. 1982 Aug;2(4):245-8 [PMID: 7119132]
  6. Can J Cardiol. 2017 Dec;33(12):1535-1542 [PMID: 29173596]
  7. J Am Coll Cardiol. 2007 Jan 30;49(4):415-21 [PMID: 17258086]
  8. Am J Psychiatry. 2002 May;159(5):728-37 [PMID: 11986125]
  9. BMC Psychol. 2022 Feb 4;10(1):20 [PMID: 35120572]
  10. J Psychosom Res. 2005 Feb;58(2):121-7 [PMID: 15820839]
  11. Pain. 2010 Mar;148(3):368-374 [PMID: 19875233]
  12. Trends Mol Med. 2015 May;21(5):285-94 [PMID: 25883069]
  13. Lancet Psychiatry. 2016 Nov;3(11):1059-1066 [PMID: 27726982]
  14. Aust J Gen Pract. 2019 Oct;48(10):700-705 [PMID: 31569323]
  15. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:191-211 [PMID: 30216744]
  16. JAMA Netw Open. 2022 Jan 4;5(1):e2143955 [PMID: 35040967]
  17. Pulm Pharmacol Ther. 2002;15(3):303-8 [PMID: 12099783]
  18. J Clin Epidemiol. 2020 Mar;119:109-116 [PMID: 31786153]
  19. J Headache Pain. 2020 Sep 25;21(1):117 [PMID: 32977761]
  20. J Invest Dermatol. 2015 May;135(5):1234-1243 [PMID: 25609025]
  21. Eval Health Prof. 2002 Dec;25(4):369-86 [PMID: 12449081]
  22. Med Clin (Barc). 2004 Apr 10;122(13):511-6 [PMID: 15104949]
  23. J Neurosci. 2021 Nov 24;41(47):9794-9806 [PMID: 34697093]
  24. Ann Surg. 1946 Jan;123(1):96-105 [PMID: 17858731]
  25. Rev Esp Anestesiol Reanim. 2017 Aug - Sep;64(7):384-390 [PMID: 28214095]
  26. Int J Epidemiol. 2018 Oct 1;47(5):1454-1464 [PMID: 29878123]
  27. Gut. 2015 Mar;64(3):418-27 [PMID: 24833636]
  28. Psychother Psychosom. 2018;87(4):204-210 [PMID: 29895014]
  29. Clin Rheumatol. 2017 Jul;36(7):1623-1630 [PMID: 28299460]
  30. Hum Psychopharmacol. 2009 Oct;24(7):549-58 [PMID: 19697301]
  31. Vaccine. 2017 Dec 14;35(49 Pt B):6872-6878 [PMID: 29128382]
  32. Ann Behav Med. 2018 Sep 13;52(10):902-908 [PMID: 30212845]
  33. Sci Transl Med. 2011 Feb 16;3(70):70ra14 [PMID: 21325618]
  34. PLoS One. 2018 Aug 24;13(8):e0202211 [PMID: 30142199]
  35. Health Soc Care Community. 2019 Jul;27(4):824-847 [PMID: 30456773]
  36. Gen Hosp Psychiatry. 2007 May-Jun;29(3):275-7 [PMID: 17484949]
  37. J Neurosci. 2007 Oct 31;27(44):11934-9 [PMID: 17978033]
  38. BMJ Evid Based Med. 2020 Apr;25(2):46-48 [PMID: 30975717]
  39. J Neurotrauma. 2018 Jun 1;35(11):1205-1212 [PMID: 29343158]
  40. Hypertension. 2015 Feb;65(2):401-6 [PMID: 25403604]
  41. F1000Res. 2019 Jan 3;8:5 [PMID: 31354941]
  42. J Headache Pain. 2007 Feb;8(1):63-6 [PMID: 17361384]
  43. Clin Pharmacol Ther. 2021 Aug;110(2):486-497 [PMID: 33894061]
  44. Int Rev Neurobiol. 2020;153:71-101 [PMID: 32563294]
  45. Lancet. 1985 Jan 5;1(8419):43 [PMID: 2856960]
  46. JAMA Netw Open. 2021 Sep 1;4(9):e2125531 [PMID: 34559231]
  47. J Affect Disord. 2020 Sep 1;274:920-928 [PMID: 32664033]
  48. Eur J Sport Sci. 2020 Apr;20(3):279-292 [PMID: 31414966]
  49. Ann Behav Med. 2019 Jan 1;53(1):16-28 [PMID: 29547962]
  50. Cardiology. 2009;112(3):174-7 [PMID: 18654082]
  51. PLoS One. 2012;7(10):e48135 [PMID: 23110189]
  52. Med J Aust. 2021 Sep 19;: [PMID: 34537963]
  53. Clin Pharmacol Ther. 1996 Sep;60(3):247-54 [PMID: 8841147]
  54. PLoS One. 2017 Sep 11;12(9):e0182466 [PMID: 28892513]
  55. J Clin Invest. 1958 Apr;37(4):533-7 [PMID: 13539192]
  56. Neuropsychopharmacology. 2015 Mar;40(4):957-65 [PMID: 25308352]
  57. Front Psychol. 2020 Oct 30;11:589884 [PMID: 33192929]
  58. BMJ. 2008 Oct 23;337:a1938 [PMID: 18948346]
  59. BMC Med. 2010 Feb 23;8:15 [PMID: 20178561]
  60. Medicines (Basel). 2020 Jan 02;7(1): [PMID: 31906435]
  61. Lancet. 2010 Feb 20;375(9715):686-95 [PMID: 20171404]
  62. Ann Behav Med. 2019 Jun 4;53(7):621-629 [PMID: 30204841]
  63. Pain. 2011 Aug;152(8):1709-1717 [PMID: 21429668]
  64. Front Psychiatry. 2020 Mar 11;11:169 [PMID: 32218746]
  65. Int Rev Neurobiol. 2020;153:103-120 [PMID: 32563284]
  66. J Clin Psychopharmacol. 2009 Aug;29(4):372-7 [PMID: 19593178]
  67. J Neurosci. 2008 Dec 3;28(49):13066-74 [PMID: 19052197]
  68. Philos Trans R Soc Lond B Biol Sci. 2011 Jun 27;366(1572):1808-17 [PMID: 21576138]
  69. Sci Rep. 2021 Feb 16;11(1):3855 [PMID: 33594150]
  70. J Allergy Clin Immunol. 2007 Jun;119(6):1375-81 [PMID: 17451796]
  71. J Clin Psychiatry. 2015 Apr;76(4):e534-6 [PMID: 25919852]
  72. Int Rev Neurobiol. 2018;139:357-378 [PMID: 30146054]
  73. N Engl J Med. 2015 Jul 2;373(1):8-9 [PMID: 26132938]
  74. PLoS One. 2013;8(3):e58247 [PMID: 23526969]
  75. Front Psychiatry. 2020 Aug 26;11:849 [PMID: 33005155]
  76. Eur Urol. 2006 Sep;50(3):440-52; discussion 453 [PMID: 16753253]
  77. Dig Liver Dis. 2010 Sep;42(9):616-9 [PMID: 20227928]
  78. BMJ. 2012 Dec 17;345:e8343 [PMID: 23248080]
  79. Br J Anaesth. 2019 Aug;123(2):e254-e262 [PMID: 30915982]
  80. BMJ. 2008 May 3;336(7651):999-1003 [PMID: 18390493]
  81. Int Rev Neurobiol. 2020;153:27-47 [PMID: 32563291]
  82. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD003974 [PMID: 20091554]
  83. Front Psychiatry. 2019 Jun 13;10:407 [PMID: 31249537]
  84. Cult Med Psychiatry. 2009 Mar;33(1):112-52 [PMID: 19107582]
  85. N Engl J Med. 1969 Jul 3;281(1):16-9 [PMID: 4891641]
  86. Pharmacol Res Perspect. 2016 Mar 17;4(2):e00208 [PMID: 27069627]
  87. J Psychiatr Res. 2021 Nov;143:528-533 [PMID: 33243457]
  88. Neurosci Biobehav Rev. 2008;32(4):852-62 [PMID: 18295886]
  89. Adv Med Educ Pract. 2020 Sep 09;11:619-635 [PMID: 32982535]
  90. Sci Rep. 2015 Nov 25;5:17140 [PMID: 26602173]
  91. J Sleep Res. 2017 Dec;26(6):675-700 [PMID: 28875581]
  92. J Neural Transm (Vienna). 2020 Apr;127(4):687-696 [PMID: 31758266]
  93. Am J Cardiol. 1960 Apr;5:483-6 [PMID: 13816818]
  94. Psychol Med. 2005 May;35(5):743-9 [PMID: 15918351]
  95. Int Rev Neurobiol. 2018;138:39-59 [PMID: 29681334]
  96. BMC Med. 2020 Nov 16;18(1):322 [PMID: 33190640]
  97. N Engl J Med. 2018 Nov 22;379(21):2002-2014 [PMID: 30462938]
  98. Eur J Heart Fail. 2013 Dec;15(12):1419-28 [PMID: 24259043]
  99. Neuron. 2007 Jul 19;55(2):325-36 [PMID: 17640532]
  100. Curr Psychiatry Rep. 2011 Feb;13(1):37-42 [PMID: 20878506]
  101. J Clin Psychiatry. 2012 Oct;73(10):1322-5 [PMID: 23140650]
  102. Clin Ther. 2017 Mar;39(3):477-486 [PMID: 28237673]
  103. Int J Environ Res Public Health. 2021 Jun 01;18(11): [PMID: 34205985]
  104. Curr Allergy Asthma Rep. 2014 Aug;14(8):456 [PMID: 24951239]
  105. J Physiol. 2016 Oct 1;594(19):5647-60 [PMID: 26861164]
  106. Aliment Pharmacol Ther. 2010 Jul;32(1):29-42 [PMID: 20353496]
  107. J Dev Behav Pediatr. 2010 Jun;31(5):369-75 [PMID: 20495473]
  108. N Engl J Med. 2020 Feb 6;382(6):554-561 [PMID: 32023375]
  109. BMC Pediatr. 2019 Jan 10;19(1):15 [PMID: 30630461]
  110. Pain. 2006 Sep;124(1-2):126-33 [PMID: 16701952]
  111. JAMA. 2002 Feb 6;287(5):622-7 [PMID: 11829702]
  112. Physiol Rev. 2013 Jul;93(3):1207-46 [PMID: 23899563]
  113. Lancet Psychiatry. 2015 Mar;2(3):246-57 [PMID: 25815249]
  114. Arch Intern Med. 2006 Jan 23;166(2):155-60 [PMID: 16432082]
  115. Lancet. 2005 Aug 27-Sep 2;366(9487):726-32 [PMID: 16125589]
  116. J Neurosci. 2005 Aug 31;25(35):7896-904 [PMID: 16135746]
  117. Psychiatry Res. 2014 Jan 30;215(1):82-6 [PMID: 24210741]
  118. BMJ Open. 2015 Dec 11;5(12):e009655 [PMID: 26656986]
  119. Encephale. 2016 Feb;42(1 Suppl 1):1S24-30 [PMID: 26879253]
  120. Clin Gastroenterol Hepatol. 2006 Nov;4(11):1302-8 [PMID: 17081807]
  121. Lancet. 1994 Oct 22;344(8930):1140-2 [PMID: 7934500]
  122. Br J Health Psychol. 2020 Sep;25(3):596-614 [PMID: 32472982]
  123. Sci Rep. 2020 Nov 18;10(1):20090 [PMID: 33208855]
  124. Psychosom Med. 2017 May;79(4):388-394 [PMID: 27922566]
  125. Pediatr Res. 2017 Jan;81(1-1):11-17 [PMID: 27648807]
  126. Curr Atheroscler Rep. 2020 Jun 18;22(8):37 [PMID: 32557172]
  127. BMJ. 2011 Aug 11;343:d4345 [PMID: 21835868]
  128. Nat Rev Neurosci. 2015 Jul;16(7):403-18 [PMID: 26087681]
  129. J Am Coll Cardiol. 2021 Sep 21;78(12):1210-1222 [PMID: 34531021]
  130. J Psychiatr Res. 2012 Jun;46(6):697-702 [PMID: 22410207]

MeSH Term

Humans
Nocebo Effect
Physician-Patient Relations
Placebo Effect

Word Cloud

Created with Highcharts 10.0.0placeboeffectuseclinicalcanPlaceboprovideupdatedpracticenocebopointmultiplealthoughassociatedtreatmentadditionaimsinformationplacebo/nocebopotentialarticleroughoverviewintendedservestartingreadergodeepercorrespondingliteratureobservedmedicalconditionsoraladministrationmanualtherapieswellsurgeryinvasiveprocedurestrialsfundamentalethicsdiscussionmaybehavelikedrugpharmacokineticpharmacodynamicviewalsoadverseeventsmodifyincreasingdecreasingeffectsdrugsfactorsoccurrencedependdoctor-patientrelationshipimportantresultfindingspublishedlasttwodecadespsycho-neurobiologicalbasisbecomingbetterunderstoodstudiesneededconclusionclinicexhibitsweakmoderateintensitytrialconsideredanothertherapeuticremedyeitherstandaloneassociationusefulcertaincircumstancesregulatedEuropeanhealthauthoritiesguidewillimprovepatientcarePlacebo:briefreviewHistorymedicineNeuropsychiatryNoceboPain

Similar Articles

Cited By