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A '''placebo''' ({{IPAc-en|p|l|ə|ˈ|s|iː|b|oʊ}} {{respell|plə|SEE|boh}}) is a substance or treatment which is designed to have no therapeutic value.<ref name=aspmn/> Common placebos include inert tablets (like sugar pills), inert injections (like [[Saline (medicine)|saline]]), [[sham surgery]],<ref>{{cite web | url=https://www.wsj.com/articles/SB10001424052702304680904579365414108916816 | title=The FDA Wants You for Sham Surgery | work=Wall Street Journal | date=18 February 2014 | access-date=8 January 2015 | last = Gottlieb | first = Scott }}</ref> and other procedures.<ref name="Lanotte">{{cite journal | vauthors = Lanotte M, Lopiano L, Torre E, Bergamasco B, Colloca L, Benedetti F | title = Expectation enhances autonomic responses to stimulation of the human subthalamic limbic region | journal = Brain, Behavior, and Immunity | volume = 19 | issue = 6 | pages = 500–509 | date = November 2005 | pmid = 16055306 | doi = 10.1016/j.bbi.2005.06.004 | s2cid = 36092163 }}</ref>
Placebos are used in [[Randomized controlled trial|randomized clinical trials]] to test the efficacy of [[Drug|medical treatments]]. In a [[Placebo-controlled study|placebo-controlled]] [[clinical trial]], any change in the [[scientific control|control]] group is known as the ''placebo response'', and the difference between this and the result of no treatment is the ''placebo effect''.<ref name="chaplin" /> Placebos in clinical trials should ideally be indistinguishable from so-called verum treatments under investigation, except for the latter's particular hypothesized medicinal effect.<ref>{{Cite journal |last1=Blease |first1=Charlotte |last2=Annoni |first2=Marco |date=April 2019 |title=Overcoming disagreement: a roadmap for placebo studies |url=https://www.researchgate.net/publication/331766597 |journal=Biology & Philosophy |language=en |volume=34 |issue=2 |doi=10.1007/s10539-019-9671-5 |issn=0169-3867}}</ref> This is to [[blinded experiment|shield test participants]] (with their [[consent]]) from knowing who is getting the placebo and who is getting the treatment under test, as patients' and clinicians' expectations of [[efficacy]] can influence results.<ref>{{cite web |date=9 April 2016 |title=placebo |url=http://www.dictionary.com/browse/placebo |access-date=21 January 2017 |work=Dictionary.com}}</ref><ref>{{cite web |title=placebo |url=http://www.thefreedictionary.com/placebo |access-date=21 January 2017 |work=TheFreeDictionary.com}}</ref>
The idea of a placebo effect was discussed in 18th century psychology,<ref>Schwarz, K. A., & Pfister, R.: ''Scientific psychology in the 18th century: a historical rediscovery.'' In: ''Perspectives on Psychological Science'', Nr. 11, pp. 399–407.</ref> but became more prominent in the 20th century. Modern studies find that placebos can affect some outcomes such as [[pain]] and [[nausea]], but otherwise do not generally have important clinical effects.<ref name="CochraneHrob2010" /> Improvements that patients experience after being treated with a placebo can also be due to unrelated factors, such as [[regression to the mean]] (a statistical effect where an unusually high or low measurement is likely to be followed by a less extreme one).<ref name="acs" /> The use of placebos in clinical medicine raises ethical concerns, especially if they are disguised as an active treatment, as this introduces dishonesty into the doctor–patient relationship and bypasses [[informed consent]].<ref name="Newman">{{cite book |last=Newman |first=David H. |title=Hippocrates' Shadow |publisher=Scribner |year=2008 |isbn=978-1-4165-5153-9 |pages=134–159}}</ref>
==Etymology==
''Placebo''The [[Latin]] term {{lang|la|placebo}} (pronounced /plaˈkebo/ or /plaˈt͡ʃebo) is [[Latin]] formeans ''[I] shall be pleasing''. It was used as a name for the [[Vespers]] in the [[Office of the Dead]], taken from its [[incipit]], a quote from the [[Vulgate]]'s Psalm 116:9 ([[Psalm 116114]]:9 in modern bibles), ''{{lang|la|placēbō Dominō in regiōne vīvōrum''}}, "[I] shall please the Lord in the land of the living".<ref>{{Cite web|title=Placebo (origins of technical term)|url=https://www.thefreedictionary.com/Placebo+(origins+of+technical+term)|access-date=2021-02-07|website=TheFreeDictionary.com}}</ref><ref>{{Bibleverse|Psalms|114:9}}</ref><ref name=Jacobs00>{{cite journal |author=Jacobs B |title=Biblical origins of placebo |journal=Journal of the Royal Society of Medicine |volume=93 |issue=4 |pages=213–214 |date=April 2000 |pmid=10844895 |pmc=1297986 |doi=10.1177/014107680009300419 }}</ref> From that, a ''singer of placebo'' became associated with someone who falsely claimed a connection to the deceased to get a share of the funeral meal, and hence a flatterer, and so a deceptive act to please.<ref name="Shapiro"/>
==Definitions==
{{further|Alternative medicine#Perceived mechanism of effect}}
Placebos can improve patient-reported outcomes such as [[pain]] and [[nausea]].<ref name=CochraneHrob2010>{{cite journal | vauthors = Hróbjartsson A, Gøtzsche PC | title = Placebo interventions for all clinical conditions | journal = The Cochrane Database of Systematic Reviews | volume = 106 | issue = 1 | pages = CD003974 | date = January 2010 | pmid = 20091554 | doi = 10.1002/14651858.CD003974.pub3 | pmc = 7156905 | editor1-last = Hróbjartsson | editor1-first = Asbjørn | url = http://nordic.cochrane.org/sites/nordic.cochrane.org/files/public/uploads/ResearchHighlights/Placebo%20interventions%20for%20all%20clinical%20conditions%20(Cochrane%20review).pdf | access-date = 2018-06-25 | archive-date = 2019-04-02 | archive-url = https://web.archive.org/web/20190402005647/https://nordic.cochrane.org/sites/nordic.cochrane.org/files/public/uploads/ResearchHighlights/Placebo%20interventions%20for%20all%20clinical%20conditions%20(Cochrane%20review).pdf | url-status = dead }}</ref><ref>{{cite journal |last1=Benedetti |first1=Fabrizio |title=Mechanisms of Placebo and Placebo-Related Effects Across Diseases and Treatments |journal=Annual Review of Pharmacology and Toxicology |date=1 February 2008 |volume=48 |issue=1 |pages=33–60 |doi=10.1146/annurev.pharmtox.48.113006.094711 |pmid=17666008 |url=https://doi.org/10.1146/annurev.pharmtox.48.113006.094711 |access-date=17 March 2022 |issn=0362-1642}}</ref> A 2001 [[Cochrane Collaboration]] meta-analysis of the placebo effect looked at trials in 40 different medical conditions, and concluded the only one where it had been shown to have a significant effect was for pain.<ref name="Hrob2001" /> Another Cochrane review in 2010 suggested that placebo effects are apparent only in subjective, continuous measures, and in the treatment of pain and related conditions. The review found that placebos do not appear to affect the actual diseases, or outcomes that are not dependent on a patient's perception. The authors, [[Asbjørn Hróbjartsson]] and [[Peter C. Gøtzsche]], concluded that their study "did not find that placebo interventions have important clinical effects in general".<ref name="CochraneHrob2010" /> This interpretation has been subject to criticism, as the existence of placebo effects seems undeniable.<ref>{{Cite journal |last1=Vase |first1=Lene |last2=Petersen |first2=Gitte Laue |last3=Riley |first3=Joseph L. |last4=Price |first4=Donald D. |date=2009-09-01 |title=Factors contributing to large analgesic effects in placebo mechanism studies conducted between 2002 and 2007 |url=https://www.sciencedirect.com/science/article/pii/S0304395909002164 |journal=PAIN |volume=145 |issue=1 |pages=36–44 |doi=10.1016/j.pain.2009.04.008 |issn=0304-3959 |pmid=19559529 |s2cid=5790594}}</ref><ref>{{Cite journal |last1=Spiegel |first1=D |last2=Kraemer |first2=H |last3=Carlson |first3=R W |date=2001-10-01 |title=Is the placebo powerless |url=https://doi.org/10.1056/NEJM200110253451712 |journal=The New England Journal of Medicine |volume=345 |issue=17 |pages=1276; author reply 1278–9 |doi=10.1056/nejm200110253451712 |issn=1533-4406 |pmid=11680452}}</ref><ref>{{Cite web |title=APA PsycNet |url=https://psycnet.apa.org/record/2001-05525-013 |access-date=2023-09-16 |website=psycnet.apa.org |language=en}}</ref><ref>{{Cite journal |last1=Wampold |first1=Bruce E. |last2=Imel |first2=Zac E. |last3=Minami |first3=Takuya |date=April 2007 |title=The story of placebo effects in medicine: Evidence in context |url=https://onlinelibrary.wiley.com/doi/10.1002/jclp.20354 |journal=Journal of Clinical Psychology |language=en |volume=63 |issue=4 |pages=379–390 |doi=10.1002/jclp.20354 |pmid=17279527}}</ref><ref>{{Cite journal |last1=Wampold |first1=Bruce E. |last2=Minami |first2=Takuya |last3=Tierney |first3=Sandra Callen |last4=Baskin |first4=Thomas W. |last5=Bhati |first5=Kuldhir S. |date=July 2005 |title=The placebo is powerful: Estimating placebo effects in medicine and psychotherapy from randomized clinical trials |url=https://onlinelibrary.wiley.com/doi/10.1002/jclp.20129 |journal=Journal of Clinical Psychology |language=en |volume=61 |issue=7 |pages=835–854 |doi=10.1002/jclp.20129 |issn=0021-9762 |pmid=15827993}}</ref> For example, recent research has linked placebo interventions to improved motor functions in patients with [[Parkinson's disease]].<ref name="quattrone-barbagallo">{{Cite journal|last1=Quattrone|first1=Aldo|last2=Barbagallo|first2=Gaetano|last3=Cerasa|first3=Antonio|last4=Stoessl|first4=A. Jon|date=August 2018|title=Neurobiology of placebo effect in Parkinson's disease: What we have learned and where we are going|journal=Movement Disorders |volume=33|issue=8|pages=1213–1227|doi=10.1002/mds.27438|issn=1531-8257|pmid=30230624|s2cid=52294141}}</ref><ref>{{Cite journal|last=Gross|first=Liza|date=February 2017|title=Putting placebos to the test|journal=PLOS Biology|volume=15|issue=2|pages=e2001998|doi=10.1371/journal.pbio.2001998|issn=1545-7885|pmc=5319646|pmid=28222121 |doi-access=free }}</ref><ref>{{Cite journal|last1=Enck|first1=Paul|last2=Bingel|first2=Ulrike|last3=Schedlowski|first3=Manfred|last4=Rief|first4=Winfried|date=March 2013|title=The placebo response in medicine: minimize, maximize or personalize?|url=https://www.researchgate.net/publication/235756144|journal=Nature Reviews Drug Discovery|language=en|volume=12|issue=3|pages=191–204|doi=10.1038/nrd3923|pmid=23449306|s2cid=24556504|issn=1474-1776}}</ref> Other objective outcomes affected by placebos include [[Immune system|immune]] and [[Endocrine system|endocrine]] parameters,<ref name=":1">{{Cite journal |last1=Tekampe |first1=Judith |last2=van Middendorp |first2=Henriët |last3=Meeuwis |first3=Stefanie H. |last4=van Leusden |first4=Jelle W.R. |last5=Pacheco-López |first5=Gustavo |last6=Hermus |first6=Ad R.M.M. |last7=Evers |first7=Andrea W.M. |date=2017-02-10 |title=Conditioning Immune and Endocrine Parameters in Humans: A Systematic Review |journal=Psychotherapy and Psychosomatics |volume=86 |issue=2 |pages=99–107 |doi=10.1159/000449470 |issn=0033-3190 |pmid=28183096 |s2cid=40594851 |doi-access=free |hdl-access=free |hdl=2066/170318}}</ref><ref name="Pacheco" /> end-organ functions regulated by the [[autonomic nervous system]],<ref>{{Cite journal |last=Meissner |first=Karin |date=2011-06-27 |title=The placebo effect and the autonomic nervous system: evidence for an intimate relationship |journal=Philosophical Transactions of the Royal Society B: Biological Sciences |volume=366 |issue=1572 |pages=1808–1817 |doi=10.1098/rstb.2010.0403 |issn=0962-8436 |pmc=3130407 |pmid=21576138}}</ref> and [[sport]] performance.<ref>{{Cite journal |last1=Hurst |first1=Philip |last2=Schipof-Godart |first2=Lieke |last3=Szabo |first3=Attila |last4=Raglin |first4=John |last5=Hettinga |first5=Florentina |last6=Roelands |first6=Bart |last7=Lane |first7=Andrew |last8=Foad |first8=Abby |last9=Coleman |first9=Damian |last10=Beedie |first10=Chris |date=2020-03-15 |title=The Placebo and Nocebo effect on sports performance: A systematic review |url=https://www.tandfonline.com/doi/full/10.1080/17461391.2019.1655098 |journal=European Journal of Sport Science |language=en |volume=20 |issue=3 |pages=279–292 |doi=10.1080/17461391.2019.1655098 |issn=1746-1391 |pmid=31414966 |s2cid=199662279 |hdl-access=free |hdl=2436/622641}}</ref>
Placebos are believed to be capable of altering a person's perception of pain. According to the American Cancer Society, "A person might reinterpret a sharp pain as uncomfortable tingling."<ref name="acs" />
===Factors influencing the power of the placebo effect===
A review published in ''[[JAMA Psychiatry]]'' found that, in trials of antipsychotic medications, the change in response to receiving a placebo had increased significantly between 1960 and 2013. The review's authors identified several factors that could be responsible for this change, including inflation of baseline scores and enrollment of fewer severely ill patients.<ref>{{cite journal | vauthors = Rutherford BR, Pott E, Tandler JM, [[Melanie Wall|Wall MM]], Roose SP, Lieberman JA | title = Placebo response in antipsychotic clinical trials: a meta-analysis | journal = JAMA Psychiatry | volume = 71 | issue = 12 | pages = 1409–21 | date = December 2014 | pmid = 25321611 | pmc = 4256120 | doi = 10.1001/jamapsychiatry.2014.1319 }}</ref> Another analysis published in ''Pain'' in 2015 found that placebo responses had increased considerably in [[neuropathic pain]] clinical trials conducted in the United States from 1990 to 2013. The researchers suggested that this may be because such trials have "increased in study size and length" during this time period.<ref>{{cite journal | vauthors = Tuttle AH, Tohyama S, Ramsay T, Kimmelman J, Schweinhardt P, Bennett GJ, Mogil JS | title = Increasing placebo responses over time in U.S. clinical trials of neuropathic pain | journal = Pain | volume = 156 | issue = 12 | pages = 2616–26 | date = December 2015 | pmid = 26307858 | doi = 10.1097/j.pain.0000000000000333 | s2cid = 23246031 }}
* {{lay source |template = cite magazine|vauthors = Dahl M |url= https://www.thecut.com/2015/10/placebo-effect-is-getting-stronger.html|title = The Placebo Effect Is Getting Stronger — But Only in the U.S.|date = October 9, 2015 |website = The Cut}}</ref>
=== Depression ===
In 2008, a controversial meta-analysis led by psychologist [[Irving Kirsch]], analyzing data from the [[Food and Drug Administration]] (FDA), concluded that 82% of the response to antidepressants was accounted for by placebos.<ref>{{cite journal | vauthors = Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT | title = Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration | journal = PLOS Medicine | volume = 5 | issue = 2 | pages = e45 | date = February 2008 | pmid = 18303940 | pmc = 2253608 | doi = 10.1371/journal.pmed.0050045 | doi-access = free }}</ref> However, thereother authors areexpressed serious doubts about the used methods and the interpretation of the results, especially the use of 0.5 as the cut-off point for the [[effect size]].<ref name="TurnerRosenthal2008">{{cite journal | vauthors = Turner EH, Rosenthal R | title = Efficacy of antidepressants | journal = BMJ | volume = 336 | issue = 7643 | pages = 516–7 | date = March 2008 | pmid = 18319297 | pmc = 2265347 | doi = 10.1136/bmj.39510.531597.80 }}</ref> A complete reanalysis and recalculation based on the same FDA data discoveredfound that the Kirsch study had "important flaws in the calculations". The authors concluded that although a large percentage of the placebo response was due to expectancy, this was not true for the active drug. Besides confirming drug effectiveness, they found that the drug effect was not related to depression severity.<ref name="FountoulakisMöller2010">{{cite journal | vauthors = Fountoulakis KN, Möller HJ | title = Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data | journal = The International Journal of Neuropsychopharmacology | volume = 14 | issue = 3 | pages = 405–12 | date = April 2011 | pmid = 20800012 | doi = 10.1017/S1461145710000957 | doi-access = free }}</ref>
Another meta-analysis found that 79% of depressed patients receiving placebo remained well (for 12 weeks after an initial 6–8 weeks of successful therapy) compared to 93% of those receiving antidepressants. In the continuation phase however, patients on placebo relapsed significantly more often than patients on antidepressants.<ref>{{cite journal | vauthors = Khan A, Redding N, Brown WA | title = The persistence of the placebo response in antidepressant clinical trials | journal = Journal of Psychiatric Research | volume = 42 | issue = 10 | pages = 791–6 | date = August 2008 | pmid = 18036616 | doi = 10.1016/j.jpsychires.2007.10.004 }}</ref>
{{main|Nocebo}}
A phenomenon opposite to the placebo effect has also been observed. When an inactive substance or treatment is administered to a recipient who has an expectation of it having a ''negative'' impact, this intervention is known as a '''nocebo''' ([[Latin]] ''{{lang|la|nocebo''}} = "I shall harm").<ref>{{cite web|url=https://www.merriam-webster.com/dictionary/nocebo|title=nocebo|access-date=22 January 2017|publisher=MirriamMerriam-Webster Incorporated}}</ref> A '''nocebo effect''' occurs when the recipient of an inert substance reports a negative effect or a worsening of symptoms, with the outcome resulting not from the substance itself, but from negative expectations about the treatment.<ref>{{cite journal | vauthors = Häuser W, Hansen E, Enck P | title = Nocebo phenomena in medicine: their relevance in everyday clinical practice | journal = Deutsches Ärzteblatt International | volume = 109 | issue = 26 | pages = 459–65 | date = June 2012 | pmid = 22833756 | pmc = 3401955 | doi = 10.3238/arztebl.2012.0459 }}</ref><ref name="autogenerated4">{{cite web |url=http://priory.com/medicine/Nocebo.htm |title=The Nocebo Effect |publisher=Priory.com |date=10 February 2007 |access-date=2009-07-08}}</ref>
Another negative consequence is that placebos can cause [[Adverse effect (medicine)|side-effects]] associated with real treatment.<ref>{{cite journal |vauthors=Shapiro AK, Chassan J, Morris LA, Frick R |year=1974 |title=Placebo induced side effects |journal=Journal of Operational Psychiatry |volume=6 |pages=43–6 |url=http://psycnet.apa.org/?fa=main.doiLanding&uid=1977-04006-001 }}</ref>
[[Category:Clinical research]]
[[Category:Deception]]
[[Category:Ethically disputed medical practices]]
[[Category:Mind–body interventions]]
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