Date: September 2012 Authr: Candidate 1 Institute: Featherstne Sixth Frm T what extent are placebs an effective methd f treatment fr pain?
EPQ Reprt Cntents Abstract ii Intrductin What is the placeb effect? 3 Hw the placeb effect wrks neurlgically t cmbat pain 5 Clinical trial prcedures 6 Ethical cncerns with placebs fr pain 7 Effectiveness f placebs 9 Cnclusin 11 Abstract THE ACTION OF PLACEBOS UPON MU OPIOD RECEPTORS BEING BLOCKED BY INDIGENOUS OPIODS SUCH AS ENDORPHINS CAUSES THE PLACEBO RESPONSE KNOWN AS PLACEBO ANALGESIA. LOOKING INTO WHETHER THIS IS AN EFFECTIVE METHOD OF TREATMENT OF PAIN IN A CLINICAL ENVIRONMENT RAISES MANY CONCERNS. THIS INCLUDES WHETHER IT WOULD BE ETHICAL AND ALSO WHETHER THERE IS A HIGH EFFICACY RATE FOR THE SPECIFIC TREATMENT OF THAT CONDITION. ON THE WHOLE THE TREATMENT IS VERY UNPREDICTABLE IN SOME CASES. THEREFORE IT SHOULD IDEALLY ONLY BE USED IN CASES WHERE ALL OTHER TREATMENTS METHODS HAVE BEEN EXHAUSTED AND THE PLACEBO IS A LAST RESORT. ii 2
EPQ Reprt Intrductin What is the placeb effect? A placeb respnse is any and all measured effects ther than a physilgical respnse t the treatment itself, 1 as defined during clinical trials. This is t say the placeb effect is all the perceived physical and mental respnses f the bdy after a treatment has been administered. Treatments that can initiate placeb respnses include inert substances such as sugar pills, sham surgeries/therapies and even the active treatments used within the healthcare prfessin. Hwever the effects f active treatments are nt cunted as part f the placeb effect. It is dubbed as the mind ver matter effect, meaning the mind is respnsible fr any changes and nt the substance r treatment given. Miscnceptins Since the placeb effect is phenmenn that has attracted a lt f attentin, with that it has als generated many miscnceptins amngst the general public and scientific cmmunity. Fr instance, there is n single placeb effect t talk f, but there are multiple effects initiated by placebs within the bdy. A lt f peple believe that prescriptins f placebs will directly cure the ailment; hwever the respnse affects the symptms being experienced. Anther miscnceptin is that patients receiving placebs must nt be aware that they are receiving an inactive r ineffective treatment r they will nt be fled int believing they are making a recvery. Patients can in fact be tld they are receiving a placeb, and still experience an alleviatin f symptms if they receive an explanatin as t hw t the placeb effect takes place, hwever this methd can reduce success rates, but remves the ethical cncern f deceiving a patient. Als, there is a belief that the placeb effect cannt ccur in small children and animals, hwever due t bserver bias, the persn interpreting the results f the treatment in children and animals may perceive an imprvement meaning there was a placeb respnse since it is subject t the behlder. Clearing these miscnceptins enables a clear understanding f the placeb respnse, t be able t make a judgement n whether it is in fact an effective and viable methd f treatment. What cnditins are affected by placebs? Placebs can affect an array f cnditins, bth by aiding recvery r even inducing mre negative effects (knwn as the nceb effect). The effect ccurs in varying strengths depending upn the cnditin. Sme psychlgical cnditins such as pain, depressin and anxiety especially have been knwn t prduce very strng placeb respnses due t the areas f the brain which are activated. Sme f the many cnditins fr which the placeb effects have been studied and prven t exist fr include: Asthma Autism Biplar Mania Binge Eating Disrder Depressin 3
EPQ Reprt Epilepsy Fd Allergies Hypertensin Irritable Bwel Syndrme Nausea Pain Pathlgical gambling Rheumatic diseases There are many mre cnditins fr which placeb respnses ccur, all with varying degrees f success. Althugh the effect is nt seen in all peple, it undeniably ccurs in sme, therefre prving its existence. While placebs respnses can exist in cases f cancer, they are very uncmmn, which may be influenced by many factrs. Factrs influencing the placeb effect Simply prescribing a placeb fr a cnditin, withut explaining what the treatment is suppsed t d, will lead t a very weak r even n placeb respnse. The effect is dependent n many factrs and therefre there are different types f placebs effects that are thught t ccur. Smething such as a visit t the dctrs can trigger the expectancy f imprvement f a cnditin leading patients t feel better, as the mind is put int a psychlgical state fcusing n wellbeing. This is ne f the basic principles behind the placeb effect, whereby belief leads t what is thught t be recvery as sme f the symptms are eased. This explains why when dctrs explain the mechanisms f a treatment and hw it will help, that a greater number f patients experience a psitive effect. The fallacy f treatments, r hw effective it lks, can affect hw intense a placeb respnse is. An injectin wuld prduce a greater respnse cmpared t a pill as the patient wuld think they are receiving a strnger treatment and believe their cnditin will imprve rapidly. Smetimes when a placeb has been prescribed t a patient many illness will imprve f their wn accrd ver time. As the cnditin naturally eases, peple assume it t be due t placeb and experience psitive feedback, fuelling the recvery prcess. If a persn has previus experience f a drug wrking in his favur, if the drug is re-prescribed, but replaced with an inert placeb, the mind is prepared fr recvery and the patient readily experiences imprvements. This type f placeb effect is a learned respnse after persnal experience (and) is called the cnditining effect. 2 In ther cases, the placeb effect may be explained by ther factrs that aided recvery, such as changes in lifestyle by partaking in regular exercise and eating a balanced diet while taking the treatment. This highlights that there are many factrs that must be cnsidered when using placebs as a methd f treatment and it can be difficult t achieve them all. Nceb Effect The psitive placeb effect can als wrk in reverse, knwn as the nceb effect, causing negative side effects t appear r a wrsening in symptms. Simply being made aware f the pssible side effects that can ccur as a result f a treatment, can cause expectancy and lead t them surfacing during the recvery perid. Patients wh disbelieve that a treatment will wrk and have a negative attitude twards it can experience a wrsening f their symptms, because f their mentality r simply a 4
EPQ Reprt cincidental wrsening f symptms. 3 The factrs influencing the placeb effect als apply t the nceb. Fr example, the mre strng/dangerus a pill lks, the mre likely the patient is expecting the side effects mentined t appear. Als if a patient has had a negative respnse t a treatment in the past, they will be wary f it and experience the cnditining effect. Hw the placeb effect wrks neurlgically t cmbat pain? The placeb effect is a psychlgical phenmenn, which is linked t brain stimulatin and activatin f certain areas f the brain. It has lng been hypthesised that the areas f the brain which are activated can cause a release f natural painkillers t alleviate symptms. Als stimulatin f certain areas f the brain with a placeb acts as a distractin and draw attentin away frm pain sensing regins, causing a reductin in the amunt f pain felt by a patient. What is pain? T understand hw a placeb can wrk against pain in the bdy, the cncept f pain must be clarified. Pain is a subjective experience, which means t be able t measure the amunt present; it depends upn cmparisn f pain levels felt by a test subject. Smebdy invlved in placeb analgesia research wuld be expsed t a surce f pain and then be given a placeb. Upn re-expsure t the same surce at the same intensity, the subject wuld be able t frm a cmparisn f whether there was a decrease/increase in the amunt f pain that they experience. This methd can shw that peple are able t withstand the same intensity f pain and yet reprt a decrease in pain experienced when given a placeb, prving that pain is nly as painful as yu think it is. Pain is picked up by sensry neurnes and its severity is determined by nciceptrs (pain receptrs). An impulse is carried up t the spinal crd, where reflexes can kick in withut cnscius chice f the brain. In the case where the impulse has travelled thrugh the spine and int the brain, it is interpreted by different areas f the brain. Dependant n what part f the brain is stimulated, respnses can include emtins being evked and tears being released. Painkillers are the mst cnventinal methd f blcking pain, as the drugs act upn the central nervus system by blcking synapses in nerves t stp impulses reaching the brain. They als inhibit receptrs that are invlved in pain sensry. As in many cases where drug treatments have been reprted t nt be wrking, placebs can als prduce a similar effect, making them a useful alternative. Pain is ne f the bdy s natural defences and it is a warning system fr when the bdy is being harmed, preventing and prtecting frm injuries. There have been cases where peple are brn with mutatins in their SCN9A gene, which blcks pathways t certain types f pain. A reduced sensitivity t extreme temperatures is mst cmmnly experienced and can lead t the sufferers f the mutatin t get burnt withut realising. 4 In essence, pain is an essential functin f the human bdy and when it is hindered, it is a hazard that can lead t harm. Hwever when the bdy is cnstantly at its pain threshld in thse wh suffer frm chrnic pain, it can negatively affect the persn s quality f life t a pint where they are unable t cpe with simple daily life tasks. This means that pain can be very dminating in the lives 5
EPQ Reprt f sme and drastic measures may need t be taken t relieve it, which is an argument fr why placebs may need t be used. Hw placeb analgesia takes place in the brain? Brain imaging (fmri) frm the Zubieta study shwed that activatin f μ-piid receptr-mediated neurtransmissin was bserved in bth higher-rder and sub-crtical brain regins, which included the pregenual and subgenual rstral anterir cingulate, the drslateral prefrntal crtex, the insular crtex, and the nucleus accumbens. The activatin f the receptrs in these areas f the brain reduced pain sensry and pain intensity experienced. 5 Opiids are psychactive chemicals that bind t the piid receptrs that are lcated in the bdy. One f the wrld s ldest knwn drugs includes the pium pppy, which was used as a painkiller. The bdy is knwn t have its wn endgenus piids, mst cmmnly endrphins. 6 Endrphins therefre display similar effects t piates such as analgesia and a feeling f well-being. The μ-piid receptrs have a high affinity fr β-endrphins which cause the receptrs in the areas f the brain circled in the diagrams abve t be activated, prducing an analgesic effect. Clinical Trial Prcedures Clinical trials are the extensive testing perid f pharmaceuticals, therapies, surgeries, medical devices, and nutritinal changes befre they are released nt the market. Prducers f the new treatment need t be sure it is effective and safe fr the general public t cnsume with minimal side effects. The primary principal f these trials is t learn, rather than treat patients 7 wh have signed up t the trial, althugh every care is taken t ensure the safety f the participant. The new treatments are tested fr efficacy and safety against existing treatments r placebs. 6
EPQ Reprt Placeb cntrlled trials In cases where placebs are used as the cntrl, there are blind studies in which subjects are chsen t take a treatment. Sme f the grup are given an actual treatment and thers are given an inert placeb, but the test subjects d nt knw what they are taking t keep the trial fair. This allws the testers t see all effects that are accunt fr by placeb respnses in the placeb cntrlled grup that d nt depend n the treatment. It is then pssible t determine whether the treatment was effective. These are knwn as blinded placeb trials. Anther type f placeb trial is the duble blinded placeb trials. This is where bth patients and dctrs prescribing placebs d nt knw whether the treatment is a placeb. This cancels ut the effects f the dctr s disbelief in the inactive treatment which can transfer t the patient and deter a placeb respnse as the patient can pick up the dctrs mentality twards the treatment. Als n the reverse side, the fact that the dctr knws he has prescribed a placeb, he may perceive an imprvement in the patient if he is lking fr it frm the thery f the cncept. Ethical cncerns with placebs fr pain The use f placebs t treat pain has lng been an area subjected t great debate. The underlying ethical questin surrunding placeb analgesia is exactly wh can really decide whether the placeb shuld be prescribed, as there are many varying pinins. Is it up t a dctr t chse what is best fr the patient by means f deceptin even if the efficacy f a placeb is prven? There are many things t cnsider when a placeb is being prescribed t treat pain. One such cnsideratin wuld be the amunt f pain the individual is in, because if the patient is in chrnic pain then the administratin f a placeb may be justifiable, but nt withut cnsequences. If the patient is building a tlerance t the drugs used t cntrl pain, placebs can be turned t as a last resrt t try and imprve the cnditin f the patient, as a last desperate measure t help. Als, a persn wh has sught the aid f healthcare prfessinals expects/has the right t a treatment that is based n scientific evidence and administered under truthfully and sincerely withut abusing the trust that a patient has in the healthcare wrker. Cncealed use f placebs hlds the risk f being accused fr malpractice and vilatin f infrmed cnsent legal requirements. 8 As time has gne n, medical practices have evlved in such a way that patients are much mre invlved in the decisin making f the treatments they are t receive; patients can even g as far as t refuse any and all medical treatment s lng as they are in a fit mental state t make decisins n behalf f themselves cncerning their health. The full disclsure f what treatment is being given t the patient is a requirement and failure t mentin the treatment is pharmaclgically inactive can lead t lawsuits being pursued. Case studies frm Natinal Ethics Telecnference 9 7
EPQ Reprt Case Study 1 A patient wh learned that his prescribed pain medicatin Obecalp was really placeb spelled backwards. The patient was angry that his physician deceived him, and his relatinship with his physician brke dwn cmpletely. 9 Frm the first case study it is clear that the patient felt strngly abut the deceptin invlved in his treatment leading t the deteriratin f his trust in the healthcare prfessinal respnsible and pssibly the healthcare system itself, highlighting that placebs that have been prescribed under deceptin are highly unethical, regardless f whether they have a psitive utcme. In the case that the placeb did in fact wrk, the patient wuld questin whether his pain was in fact real and whether any f the genuine pain medicatin being prescribed actually wrks. This sets a negative and disbelieving mind-frame twards healthcare which culd lead t a nceb effect in treatment fr later illnesses. Als since placebs nly aid symptms, they may be able t relieve pain, but this can be dangerus as the pain may have been an indicatr f an underlying prblem. If the pain has been dismissed, this leaves the rt f the disease untreated which can be very harmful. There are many dwnfalls t the use f placebs, hwever this des nt rule them ut as a methd f treatment. They can be given t patients in a deceptin free manner, where the patient is tld they are receiving an inactive treatment. This can still wrk if there is an explanatin prvided f hw the placeb effect wrks, althugh this can reduce efficacy f treatment. This allws the patient t chse whether they want this as a methd f treatment r wuld rather have an alternative active treatment. Clinical placeb analgesia shuld always be given as a last resrt, after exhaustive testing has been undertaken t shw there is n underlying cause f the pain, and n ther effective treatment fr it. Case Study 2 Take Michael, a 45-year-ld male experiencing chrnic back pain that is limiting his ability t wrk. A neurlgical evaluatin did nt reveal any serius abnrmalities. He has had physical therapy, chirpractic manipulatins, acupuncture, and a range f narctic and anti-inflammatry treatments. Michael was referred t the pain clinic. After carefully examining Michael and reviewing his recrds, Dr. Davis tld him abut a medicine that he generally reserves fr cmplex pain. Althugh there may be sme side effects he encuraged the patient t try it because he believed it culd wrk. The prescribed substance was a placeb. Three weeks fllwing his initial visit, Michael nted imprvement in his pain, but subsequently learned by searching WebMD that his medicatin was a sugar pill cmmnly prescribed as a placeb. Feeling cnfused and betrayed, Michael never returned t see Dr. Davis. 9 8
EPQ Reprt The central ethical cnflict fr the use f placebs is whether the truth-telling utweighs the benefits a patient may receive under deceptin. It is a grey area, with mixed views n whether a dctr shuld have dispensed inactive medicatin as this is deceiving the patient even when the treatment has psitive utcmes, as demnstrated in the secnd case study. The scenari abve shws that even when all ther therapies had been exhausted in trying t alleviate Michael s pain, his dctr resrted t a placeb. Even thugh the therapy had wrked, he clearly felt he culdn t trust the dctr as he never returned t him. Each persn will have a different reactin t finding ut they were lied t depending n their situatin, including hw much pain they were in and hw desperate they are t have it relieved. Case Study 3 During the interview I cnducted n a sufferer f chrnic pain, I fund that Ms Lynam wuld be grateful t have the pain she is experiencing in everyday life reduced, but it wuld raise a lt f questins if the treatment wrked. Fr example, she said it culd lead t her questining her mental state and whether the pain was all a prduct f her imaginatin r if it was nt a bad as she thught it t be fr all that time. Besides the stressful nature f questining herself, she wuld be cncerned with the mtives f the dctr. She wuld wnder whether the dctr tk her seriusly r thught she was ver exaggerating her cnditin. Hwever if it didn t wrk, she tld me she wuld feel a variety f emtins branching ut frm her anger. Mstly the fact that the dctr s treatment suggests he didn t take her reprts f pain seriusly, thinking she culd be tricked int feeling better, which wuld be very unsympathetic t her cnditin, adding insult t her injury. 10 Shuld placebs be used fr analgesic effects in clinical care The American Sciety fr Pain Management Nursing (ASPMN) tk a stance where they believe placebs shuld nt be prescribed during clinical care, but nly in clinical trials. 8 The main cncern is the deceptin invlved and the negative repercussin that arise as a result. Hwever, after cnsideratin f the efficacy fr the placeb n the certain type f pain, and the case f the individual, there is n reasn why placebs cannt be used as an aid t recvery, when dispensed in a deceptin-free manner. Effectiveness f placebs The effectiveness f placebs varies greatly between studies and it is said t ccur within the range f nbdy t nearly everybdy. The wide gap can be explained by the fact that the placeb effect is multifactrial. This means cnsideratin has t be taken when dispensing placebs as yu need the mst up t date rates f success, t determine whether the placeb treatment wuld wrk and whether it shuld take place. 9
EPQ Reprt During a study fr headaches, 120 ut f 199 patients receiving the placeb btained relief. In pstperative patients, 14% had pain reductin using a placeb. 11 Success rates have a wide spread when used in medical research, hwever if a placeb was t be used in a clinical setting, the efficacy statistics wuld need t be available fr the practitiner, as nt all placebs respnses are as strng as each ther. In terms f the effectiveness f placebs n cnditins rather than symptms the success rates are very lw. 2% f peple saw a direct impact n tumur develpment 12 althugh this placeb respnse can be assumed t be a result f ther factrs, such as natural recvery, rather than the placeb treatment itself, as they nly have an impact n symptms. As the effectiveness f placebs is nt a set figure it is very much up t a practitiner t decide whether a placeb wuld be a suitable methd f treatment. This culd als depend n the mentality f the patient and if they have a gd expectancy f recvery. It is nt uncmmn t see success rates that utperfrm drugs when tested in clinical trials which can cause great incnvenience t pharmaceutical cmpanies wh wuld have been spending lts f time and mney n wrking twards pharmaclgical substances. What this means fr pharmaceutical cmpanies In recent years, many f the large firms investing mney int the research and develpment f new medical breakthrughs are experiencing bitter disappintment in their testing stages when the drugs that have been created are perfrming n par r even belw the effects a placeb wuld have. This means the new drug wuld have t be drpped frm prductin. This is because when tested against placebs, the drugs prduce the same respnse s develpers cannt be sure the new drug is respnsible fr curing the cnditin via a pharmaclgical respnse r whether the drug is just prducing a placeb respnse. Drugs that are in the secnd and third phases f clinical trialling and underg develpment cuts are usually tested against placebs in these stages. The main cause fr drpping the prductin f the drug is due t pr drug respnses when cmpared against placebs. Over the perid f 2001 t 2006 the drug cmpany Merck saw a 20 percent increase in new prduct cuts when drugs were first tested against placebs in the secnd phase. The mre extensive phase three trial shwed a rise by 11 percent, mainly because f pr respnse f the drug cmpared t placebs ver the perid. 13 This shws that the drug firms are experiencing increased difficulty as the placeb respnse seems t be getting strnger. One explanatin fr this may be the fact that many mre peple in sciety are nw aware f the placeb effect, making them mre susceptible t recvery during clinical trials as they are aware f hw the prcess wrks. This makes the placeb effect a mre useful tl in treatment as a wider range f peple are aware f it, believing that it will wrk. 10
EPQ Reprt Cnclusin If the set factrs such as expectant f recvery, desire fr recvery and cnditining effects are in place, then ther variables can be adjusted t maximise the success f placeb treatment. These variables culd include any measures that can be taken t increase a patient s expectatin f recvery. This is when it is mst likely fr a successful placeb respnse ccur, highlighting hw delicate the cnditins required are. In the case f the treatment f pain, it can be tricky t decide at what pint a dctr may cnsider intrducing a placeb. This depends n hw all ther pssible treatments have wrked and if there is n success the placeb can be used as a last resrt. 11
EPQ Reprt 1 Nvella, S. (2009) Is "the" placeb effect prven. Skepticblg, [blg] 26th Octber, Available at: http://www.skepticblg.rg/2009/10/26/is-the-placeb-effect-prven/ [Accessed: 08/03/2012]. 2 Cancer.rg (2008) Placeb Effect - What is the placeb effect. [nline] Available at: http://www.cancer.rg/treatment/treatmentsandsideeffects/treatmenttypes/placeb-effect [Accessed: 29 Sep 2012]. 3 En.wikipedia.rg (n.d.) Placeb - Wikipedia, the free encyclpaedia. [nline] Available at: http://en.wikipedia.rg/wiki/placeb#nceb [Accessed: 29 Sep 2012]. 4 Tpdcumentaryfilms.cm (2012) The Secret Wrld f Pain [nline] Available at: http://tpdcumentaryfilms.cm/secret-wrld-pain/ [Accessed: 20 Sep 2012]. 5 Jneursci.rg (2005) Placeb Effects Mediated by Endgenus Opiid Activity n μ-opiid Receptrs. [nline] Available at: http://www.jneursci.rg/cntent/25/34/7754.full [Accessed: 29 Sep 2012]. 6 En.wikipedia.rg (n.d.) Opiid - Wikipedia, the free encyclpaedia. [nline] Available at: http://en.wikipedia.rg/wiki/opiid [Accessed: 29 Sep 2012]. 7 Fredtert.cm (2012) Clinical Trials Basics. [nline] Available at: http://www.fredtert.cm/clinicalresearch/clinicaltrialsbasics/clinicaltrialsbasics.htm [Accessed: 26 Sep 2012]. 8 Cggins, C. et al. (2004) Psitin statement n use f placebs in pain management. [pdf] p.1-3 Available thrugh: Internet http://www.aspmn.rg/pdfs/use%20f%20placebs.pdf [Accessed: 24/09/2012]. 9 Dr Berkwitz and Mr Suttn (Natinal Ethics Telecnference) (2004) Clinical Use f Placeb: An ethical analysis (pg. 1-2) 10 Lynam, T. (2012) Shuld placebs be prescribed fr pain? Interviewed by Candidate 1 [in persn] Suthall, 20/09/2012. 11 WRF (2006) The Pwer f Mind and the Prmise f Placeb : Wrld Research Fundatin. [nline] Available at: http://www.wrf.rg/alternative-therapies/pwer-f-mind-placeb.php [Accessed: 23 Sep 2012]. 12 News.bbc.c.uk (2003) BBC NEWS Health Scientists analyse placeb effect. [nline] Available at: http://news.bbc.c.uk/1/hi/health/2616771.stm [Accessed: 25 Sep 2012]. 13 Wired.cm (2012) Placebs Are Getting Mre Effective. Drugmakers Are Desperate t Knw Why.. [nline] Available at: http://www.wired.cm/medtech/drugs/magazine/17-09/ff_placeb_effect?currentpage=all [Accessed: 29 Sep 2012]. 12