Jump to content

Placebo

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by CAPTAIN RAJU (talk | contribs) at 20:26, 4 March 2016 (Reverted 1 edit by 206.15.234.162 identified as test/vandalism using STiki). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Error: no context parameter provided. Use {{other uses}} for "other uses" hatnotes. (help).

"Sugar pill" redirects here. For Kids of 88 album, see Sugarpills.
The placebo effect can be produced by inert tablets, by sham surgery, and by false information, such as when electrical stimulation is turned "off" in those with Parkinson's disease implanted brain electrodes.[1]

A placebo (/pləˈsiboʊ/ plə-SEE-boh; Latin placēbō, "I shall please"[2] from placeō, "I please")[3][4] is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient. Sometimes patients given a placebo treatment will have a perceived or actual improvement in a medical condition, a phenomenon commonly called the placebo effect or placebo response. The placebo effect consists of several different effects woven together, and the methods of placebo administration may be as important as the administration itself.[5]

Placebos are an important methodological tool in medical research.[6] Common placebos include inert tablets, vehicle infusions, sham surgery,[7] and other procedures based on false information.[1] However, placebos may also have positive effect on the subjective experience of a patient who knows that the given treatment is without any active drug, as compared with a control group who knowingly did not get a placebo.[8] It has also been shown that use of therapies about which patients are unaware is less effective than using ones that patients are informed about.[9] Placebo effects are the subject of scientific research aiming to understand underlying neurobiological mechanisms of action in pain relief, immunosuppression, Parkinson's disease and depression.[10]

The placebo effect is a pervasive phenomenon;[11] in fact, it is part of the response to any active medical intervention.[12] The placebo effect points to the importance of perception and the brain's role in physical health. Placebos can produce some objective physiological changes, such as changes in heart rate, blood pressure, and chemical activity in the brain, in cases involving pain, depression, anxiety, fatigue, and some symptoms of Parkinson’s. In other cases, like asthma, the effect is purely subjective, when the patient reports improvement despite no objective change in the underlying condition.[13][14] The use of placebos as treatment in clinical medicine (as opposed to laboratory research) is ethically problematic as it introduces deception and dishonesty into the doctor-patient relationship.[15] The United Kingdom Parliamentary Committee on Science and Technology has stated that: "...prescribing placebos... usually relies on some degree of patient deception" and "prescribing pure placebos is bad medicine. Their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS."[16]

In 1955, Henry K. Beecher proposed that placebos could have clinically important effects.[17][18] This view was notably challenged when, in 2001, a systematic review of clinical trials concluded that there was no evidence of clinically important effects, except perhaps in the treatment of pain and continuous subjective outcomes.[18] The article received a flurry of criticism,[19] but the authors later published a Cochrane review with similar conclusions (updated as of 2010).[20] Most studies have attributed the difference from baseline until the end of the trial to a placebo effect, but the reviewers examined studies which had both placebo and untreated groups in order to distinguish the placebo effect from the natural progression of the disease.[18]

Definitions, effects, and ethics

See also: Medical ethics and Philosophy of medicine

A placebo has been defined as "a substance or procedure… that is objectively without specific activity for the condition being treated".[21] Under this definition, a wide variety of things can be placebos and exhibit a placebo effect. The placebo effect may be a component of pharmacological therapies: Pain killing and anxiety reducing drugs that are infused secretly without an individual's knowledge are less effective than when a patient knows they are receiving them. Likewise, the effects of stimulation from implanted electrodes in the brains of those with advanced Parkinson's disease are greater when they are aware they are receiving this stimulation.[22] Sometimes administering or prescribing a placebo merges into fake medicine.

The placebo effect has sometimes been defined as a physiological effect caused by the placebo, but Moerman and Jonas have pointed out that this seems illogical, as a placebo is an inert substance that does not directly cause anything. Instead they introduced the term "meaning response" for the meaning that the brain associates with the placebo, which causes a physiological placebo effect. They propose that the placebo, which may be unethical, could be avoided entirely if doctors comfort and encourage their patients' health.[19] Ernst and Resch also attempted to distinguish between the "true" and "perceived" placebo effect, as they argued that some of the effects attributed to the placebo effect could be due to other factors.[23]

The placebo effect has been controversial throughout history. Notable medical organizations have endorsed it,[6] but in 1903 Richard Cabot concluded that it should be avoided because it is deceptive. Newman points out the "placebo paradox", – it may be unethical to use a placebo, but also unethical "not to use something that heals". He suggests to solve this dilemma by appropriating the meaning response in medicine, that is make use of the placebo effect, as long as the "one administering… is honest, open, and believes in its potential healing power".[15]

Mechanism of the effect

Because the placebo response is simply the patient response that cannot be attributed to an investigational intervention, there are multiple possible components of a measured placebo effect. These components have varying relevance depending on study design and the types of observations.[24] While there is some evidence that placebo interventions can alter levels of hormones,[25] endocannabinoids[26] or endogenous opioids,[27] other prominent components include expectancy effects, regression to the mean,[21][28] and flawed research methodologies.

Expectancy and conditioning

The placebo effect is related to expectations

The placebo effect is related to the perceptions and expectations of the patient; if the substance is viewed as helpful, it can heal, but, if it is viewed as harmful, it can cause negative effects, which is known as the nocebo effect. In 1985, Irving Kirsch hypothesized that placebo effects are produced by the self-fulfilling effects of response expectancies, in which the belief that one will feel different leads a person to actually feel different.[29] According to this theory, the belief that one has received an active treatment can produce the subjective changes thought to be produced by the real treatment. Placebos can act similarly through classical conditioning, wherein a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus.[30] Both conditioning and expectations play a role in placebo effect,[31] and make different kinds of contribution. Conditioning has a longer-lasting effect,[32] and can affect earlier stages of information processing.[33] Those that think that a treatment will work display a stronger placebo effect than those that do not, as evidenced by a study of acupuncture.[34][35]

A placebo presented as a stimulant will have this effect on heart rhythm, and blood pressure, but, when administered as a depressant, the opposite effect.[36] Perceived ergogenic aids can increase endurance,[37] speed[38] and weight-lifting ability,[39] leading to the question of whether placebos should be allowed in sport competition.[40]

Because placebos are dependent upon perception and expectation, various factors that change the perception can increase the magnitude of the placebo response. For example, studies have found that the color and size of the placebo pill makes a difference, with "hot-colored" pills working better as stimulants while "cool-colored" pills work better as depressants. Capsules rather than tablets seem to be more effective, and size can make a difference.[41] One researcher has found that big pills increase the effect[42] while another has argued that the effect is dependent upon cultural background.[43]

Motivation may contribute to the placebo effect. The active goals of an individual changes their somatic experience by altering the detection and interpretation of expectation-congruent symptoms, and by changing the behavioral strategies a person pursues.[44][45] Motivation may link to the meaning through which people experience illness and treatment. Such meaning is derived from the culture in which they live and which informs them about the nature of illness and how it responds to treatment. Research into the placebo treatment of gastric and duodenal ulcers shows that this varies widely with society.[19] The placebo effect in treating gastric ulcers is low in Brazil, higher in northern Europe (Denmark, Netherlands), and extremely high in Germany. However, the placebo effect in treating hypertension is lower in Germany than elsewhere.[46]

Placebo effect and the brain

Functional imaging upon placebo analgesia shows that it links to the activation, and increased functional correlation between this activation, in the anterior cingulate, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, the brainstem periaqueductal gray matter,[47][48][49] and the spinal cord.[50][51][52][53]

The higher brain works by regulating subcortical processes. High placebo responses link with enhanced dopamine and mu-opioid activity in the circuitry for reward responses and motivated behavior of the nucleus accumbens, and, on the converse, anti-analgesic nocebos responses were associated with deactivation in this part of the brain of dopamine and opioid release.[48] (It has been known that placebo analgesia depends upon the release in the brain of endogenous opioids since 1978.[54]) Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray[48] on spinal nociceptive reflexes, while the expectations of anti-analgesic nocebos acts in the opposite way to block this.[50]

The brain is also involved in less-studied ways upon nonanalgesic placebo effects:

  • Parkinson's disease: Placebo relief is associated with the release of dopamine in the brain.[55]
  • Depression: Placebos reducing depression affect many of the same areas that are activated by antidepressants with the addition of the prefrontal cortex[56][57]
  • Caffeine: Placebo-caffeinated coffee causes an increase in bilateral dopamine release in the thalamus.[58]
  • Glucose: The expectation of an intravenous injection of glucose increases the release of dopamine in the basal ganglia of men (but not women).[59]
  • Methylphenidate: The expectation of intravenous injection of this drug in inexperienced drug users increased the release of dopamine in the ventral cingulate gyrus and nucleus accumbens, with this effect being largest in those with no prior experience of the drug.[60]

Functional imaging upon placebo analgesia has been summarized as showing that the placebo response is "mediated by "top-down" processes dependent on frontal cortical areas that generate and maintain cognitive expectancies. Dopaminergic reward pathways may underlie these expectancies".[61] "Diseases lacking major 'top-down' or cortically based regulation may be less prone to placebo-related improvement".[62]

Brain and body

Further information: neural top down control of physiology

The brain has control over the body processes affected by placebos.

In conditioning, a neutral stimulus saccharin is paired in a drink with an agent that produces an unconditioned response. For example, that agent might be cyclophosphamide, which causes immunosuppression. After learning this pairing, the taste of saccharin by itself is able to cause immunosuppression, as a new conditioned response via neural top-down control.[63] Such conditioning has been found to affect a diverse variety of not just basic physiological processes in the immune system but ones such as serum iron levels, oxidative DNA damage levels, and insulin secretion. Recent reviews have argued that the placebo effect is due to top-down control by the brain for immunity[64] and pain.[65] Pacheco-López and colleagues have raised the possibility of "neocortical-sympathetic-immune axis providing neuroanatomical substrates that might explain the link between placebo/conditioned and placebo/expectation responses."[64]: 441 

A recent fMRI study has shown that a placebo can reduce pain-related neural activity in the spinal cord, indicating that placebo effects can extend beyond the brain.[66]

Dopaminergic pathways have been implicated in the placebo response in pain and depression.[67]

Evolved health regulation

Evolutionary medicine identifies many symptoms such as fever, pain, and sickness behavior as evolved responses to protect or enhance the recovery from infection and injury. Fever, for example, is an evolved self-treatment that removes bacteria or viruses through raised body temperature. These evolved responses, however, also have a cost that depending upon circumstances can outweigh their benefit (due to this, for example, there is a reduction in fever during malnutrition or late pregnancy). According to the health management system theory proposed by Nicholas Humphrey, the brain has been selected to ensure that evolved responses are deployed only when the cost benefit is biologically advantageous. To do this, the brain factors in a variety of information sources, including the likelihood derived from beliefs that the body will get well without deploying its costly evolved responses. One such source of information is the knowledge the body is receiving care and treatment. The placebo effect in this perspective arises when false information about medications misleads the health management system about the likelihood of getting well so that it selects not to deploy an evolved self-treatment.[68]

Clinical utility

Clinical significance

Asbjørn Hróbjartsson and Peter Gøtzsche published a study in 2001[18] and a follow-up study in 2004[69] questioning the nature of the placebo effect. The studies were performed as two meta-analyses. They found that in studies with a binary outcome, meaning patients were classified as improved or not improved, the placebo group had no statistically significant improvement over the no-treatment group. Likewise, there was no significant placebo effect in studies in which objective outcomes (such as blood pressure) were measured by an independent observer. The placebo effect could be documented only in studies in which the outcomes (improvement or failure to improve) were reported by the subjects themselves. The authors concluded that the placebo effect does not have "powerful clinical effects," (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from reporting bias. Other researchers (Wampold et al.) re-analysed the same data from the 2001 meta-analysis and concluded that the placebo effects for objective symptom measures are comparable to placebo effects for subjective ones and that the placebo effect can exceed the effect of the active treatment by 20% for disorders amenable to the placebo effect,[70][71] a conclusion which Hróbjartsson & Gøtzsche described as "powerful spin".[72] Another group of researchers noted the dramatically different conclusions between these two sets of authors despite nearly identical meta-analytic results, and suggested that placebo effects are indeed significant but small in magnitude.[73]

Hróbjartsson and Gøtzsche's conclusion has been criticised on several grounds. Their meta-analysis covered studies into a highly mixed group of conditions. It has been reported that for measurements in peripheral organs the placebo effect seems to be more effective in achieving improvements in physical parameters (such as decreasing hypertension, improving FEV1 in asthma sufferers, or decreasing prostatic hyperplasia or anal fissure) than in improving biochemical parameters (such as cholesterol or cortisol) in various conditions such as venous leg ulcers, Crohn's disease, urinary tract infection, and chronic heart failure.[74] Placebos also do not work as strongly in clinical trials because the subjects do not know whether they might be getting a real treatment or a sham one. Where studies are made of placebos in which people think they are receiving actual treatment (rather than merely its possibility) the placebo effect has been observed.[75] Other writers have argued that the placebo effect can be reliably demonstrated under appropriate conditions.[76]

In another update by Hróbjartsson & Gøtzsche, published as a 2010 Cochrane systematic review which confirms and modifies their previous work, over 200 trials investigating 60 clinical conditions were included. Placebo interventions were again not found to have important clinical effects in general but may influence patient-reported outcomes in some situations, especially pain and nausea, although it was "difficult to distinguish patient-reported effects of placebo from response bias". The pooled relative risk they calculated for placebo was 0.93 (effect of only 7%) but significant. Effects were also found for phobia and asthma but were uncertain due to high risk of bias. In other conditions involving three or more trials, there was no statistically significant effect for smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, although confidence intervals were wide. Several clinical (physical placebos, patient-involved outcomes, falsely informing patients there was no placebo) and methodological (small sample size, explicit aim of studying the placebo effect) factors were associated with higher effects of placebo. Despite low effects in general and the risk of bias, the authors acknowledged that large effects of placebo interventions may occur in certain situations.[77]

In 2013 Jeremy Howick and colleagues used Hróbjartsson & Gøtzsche's data to compare the magnitude of placebo effects with the magnitude of treatment effects.[78] They found a statistically significant difference between placebo and treatment effect sizes in trials with binary outcomes but not in trials with subjective outcomes.

Negative effects

Similar to the placebo effect, inert substances have the potential to cause negative effects via the "nocebo effect" (Latin nocebo = "I will harm"). In this effect, giving an inert substance has negative consequences.[79]

Another negative consequence is that placebos can cause side-effects associated with real treatment.[80] One example of this is with those that have already taken an opiate, can then show respiratory depression when given it again in the form of a placebo.[81]

Withdrawal symptoms can also occur after placebo treatment. This was found, for example, after the discontinuation of the Women's Health Initiative study of hormone replacement therapy for menopause. Women had been on placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 4.8% of those on placebo compared to 21.3% of those on hormone replacement.[82]

It is also often ethically challenging in practice to use placebos as a form of treatment.[83]

Doctor-patient relationship

A study of Danish general practitioners found that 48% had prescribed a placebo at least 10 times in the past year.[11] The most frequently prescribed placebos were presented as antibiotics for viral infections, and vitamins for fatigue. Specialists and hospital-based physicians reported much lower rates of placebo use. A 2004 study in the British Medical Journal of physicians in Israel found that 60% used placebos in their medical practice, most commonly to "fend off" requests for unjustified medications or to calm a patient.[84] The accompanying editorial concluded, "We cannot afford to dispense with any treatment that works, even if we are not certain how it does."[85] Other researchers have argued that open provision of placebos for treating ADHD in children can be effective in maintaining ADHD children on lower stimulant doses in the short term.[86]

Critics of the practice responded that it is unethical to prescribe treatments that do not work, and that telling a patient (as opposed to a research test subject) that a placebo is a real medication is deceptive and harms the doctor-patient relationship in the long run. Critics also argued that using placebos can delay the proper diagnosis and treatment of serious medical conditions.[87] Legitimate doctors and pharmacists could open themselves up to charges of fraud or malpractice by using a placebo.

About 25% of physicians in both the Danish and Israeli studies used placebos as a diagnostic tool to determine if a patient's symptoms were real, or if the patient was malingering. Both the critics and defenders of the medical use of placebos agreed that this was unethical.[85] The British Medical Journal editorial said, "That a patient gets pain relief from a placebo does not imply that the pain is not real or organic in origin...the use of the placebo for 'diagnosis' of whether or not pain is real is misguided."

The placebo administration may prove to be a useful treatment in some specific cases where recommended drugs cannot be used. For example, burn patients who are experiencing respiratory problems cannot often be prescribed opioid (morphine) or opioid derivatives (pethidine), as these can cause further respiratory depression. In such cases placebo injections (normal saline, etc.) are of use in providing real pain relief to burn patients if those not in delirium are told they are being given a powerful dose of painkiller.

Referring specifically to homeopathy, the House of Commons of the United Kingdom Science and Technology Committee has stated:

In the Committee's view, homeopathy is a placebo treatment and the Government should have a policy on prescribing placebos. The Government is reluctant to address the appropriateness and ethics of prescribing placebos to patients, which usually relies on some degree of patient deception. Prescribing of placebos is not consistent with informed patient choice—which the Government claims is very important—as it means patients do not have all the information needed to make choice meaningful. Beyond ethical issues and the integrity of the doctor-patient relationship, prescribing pure placebos is bad medicine. Their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS.[16]

A survey in the United States of more than 10,000 physicians came to the result that while 24% of physicians would prescribe a treatment that is a placebo simply because the patient wanted treatment, 58% would not, and for the remaining 18%, it would depend on the circumstances.[88]

Changes over time

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.[89] 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.[90]

The individual

Who is affected

Placebos do not work for everyone.[91][92] Henry K. Beecher, in a paper in 1955,[17] suggested placebo effects occurred in about 35% of people. However, this paper has been criticized for failing to distinguish the placebo effect from other factors, and for thereby encouraging an inflated notion of the placebo effect.[93]

Individual differences

In the 1950s, there was considerable research to find whether there was a specific personality to those that responded to placebos. The findings could not be replicated[94] and it is now thought to have no effect.[95]

The desire for relief from pain, "goal motivation", and how far pain is expected to be relieved increases placebo analgesia.[44] Another factor increasing the effectiveness of placebos is the degree to which a person attends to their symptoms, "somatic focus".[45] Individual variation in response to analgesic placebos has been linked to regional neurochemical differences in the internal affective state of the individuals experiencing pain.[96]

Those with Alzheimer's disease lose the capacity to be influenced by placebos, and this is attributed to the loss of their prefrontal cortex dependent capacity to have expectations.[97]

Children seem to have greater response than adults to placebos.[98]

Genes

In social anxiety disorder (SAD) an inherited variant of the gene for tryptophan hydroxylase 2 (enzyme that synthesizes the neurotransmitter serotonin) is linked to reduced amygdala activity and greater susceptibility to the placebo effect.[99][100][101] The authors note "additional work is necessary to elucidate the generalizability of the findings".

In a 2012 study, variations on the COMT (catechol-O-methyltransferase) gene related to dopamine release are found to be critical in the placebo effect among the patients with irritable bowel syndrome participating in the trial, a research group in Harvard Medical School reported. Patients with a variation of met/met, for having two copies of the methionine allele were shown to be more likely to respond to the placebo treatment, while the variation of val/val, for their two copies of valine allele responded the least. The response of patients with one copy each of methionine and valine fell in the middle. Release of dopamine in patients with the met/met variations is thought to link to reward and 'confirmation bias' which enhance the sense that the treatment is working. The role of the COMT gene variations are expected to be more prominent in studies where patients report more subjective conditions such as pain and fatigue rather than objective physiological measurements.[102][103]

Symptoms and conditions

The placebo effect occurs more strongly in some conditions than others. Dylan Evans has suggested that placebos work most strongly upon conditions such as pain, swelling, stomach ulcers, depression, and anxiety that have been linked with activation of the acute-phase response.[104]

Pain

The placebo effect is believed to reduce pain—a phenomenon known as placebo analgesia—in two different ways. One way is by the placebo initiating the release of endorphins, which are natural pain killers produced by the brain.[105] The other way is the placebo changing the patient's perception of pain. "A person might reinterpret a sharp pain as uncomfortable tingling."[106]

One way in which the magnitude of placebo analgesia can be measured is by conducting "open/hidden" studies, in which some patients receive an analgesic and are informed that they will be receiving it (open), while others are administered the same drug without their knowledge (hidden). Such studies have found that analgesics are considerably more effective when the patient knows they are receiving them.[107]

When administered orally, placebos have clinically meaningful effects with regard to lower back pain.[108]

Depression

In 2008, a controversial meta-analysis led by psychologist Irving Kirsch, analyzing data from the FDA, concluded that 82% of the response to antidepressants was accounted for by placebos.[109] However, there are serious doubts about the used methods and the interpretation of the results, especially the use of 0.5 as cut-off point for the effect-size.[110] A complete reanalysis and recalculation based on the same FDA data discovered that the Kirsch study suffered from 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.[111]

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.[112] A 2009 meta-analysis reported that in 2005 68% of the effects of antidepressants was due to the placebo effect, which was more than double the placebo response rate in 1980.[113]

While some say that blanket consent, or the general consent to unspecified treatment given by patients beforehand, is ethical, others argue that patients should always obtain specific information about the name of the drug they are receiving, its side effects, and other treatment options.[114] Even though some patients do not want to be informed, health professionals are ethically bound to give proper information about the treatment given. There is such a debate over the use of placebos because while placebos are used for the good of many to test the effectiveness of drugs, some argue that it is unethical to ever deprive individual patients of effective drugs.[115]

Chronic fatigue syndrome

It was previously assumed that placebo response rates in patients with chronic fatigue syndrome (CFS) are unusually high, "at least 30% to 50%", because of the subjective reporting of symptoms and the fluctuating nature of the condition. According to a meta-analysis and contrary to conventional wisdom, the pooled response rate in the placebo group was 19.6%, even lower than in some other medical conditions. The authors offer possible explanations for this result: CFS is widely understood to be difficult to treat, which could reduce expectations of improvement. In context of evidence showing placebos do not have powerful clinical effects when compared to no treatment, a low rate of spontaneous remission in CFS could contribute to reduced improvement rates in the placebo group. Intervention type also contributed to the heterogeneity of the response. Low patient and provider expectations regarding psychological treatment may explain particularly low placebo responses to psychiatric treatments.[116]

List of medical conditions

The effect of placebo treatments (an inert pill unless otherwise noted) has been studied for the following medical conditions. Many of these citations concern research showing that active treatments are effective, but that placebo effects exist as well. Template:Multicol

Template:Multicol-break

Template:Multicol-break

Template:Multicol-break

Template:Multicol-end

Effects on research

History

Main article: Placebo in history
A quack treating a patient with Perkins Patent Tractors by James Gillray, 1801. John Haygarth used this remedy to illustrate the power of the placebo effect.

The word 'placebo', Latin for "I will please", dates back to a Latin translation of the Bible by St Jerome.[163] In 1811, Hooper’s Quincy’s Lexicon-Medicum defined placebo as "[any medicine] adapted more to please than to benefit the patient".[164][165]

John Haygarth was the first to investigate the efficacy of the placebo effect in the 18th-century.[166] He tested a popular medical treatment of his time, called "Perkins tractors", and concluded that the remedy was ineffectual by demonstrating that the results from a dummy remedy were just as useful as from the alleged "active" remedy.[167]

Émile Coué, a French pharmacist, working as an apothecary at Troyes between 1882 and 1910, also advocated the effectiveness of the "Placebo Effect". He became known for reassuring his clients by praising each remedy's efficiency and leaving a small positive notice with each given medication. His book Self-Mastery Through Conscious Autosuggestion was published in England (1920) and in the United States (1922).

Placebos remained widespread in medicine until the 20th century, and they were sometimes endorsed as necessary deceptions.[6] In 1903, Richard Cabot said that he was brought up to use placebos,[6] but he ultimately concluded by saying that "I have not yet found any case in which a lie does not do more harm than good".[15]

In modern times, T. C. Graves first defined the "placebo effect" in a published paper in The Lancet in 1920.[168] He spoke of "the placebo effects of drugs" being manifested in those cases where "a real psychotherapeutic effect appears to have been produced".[169] In 1961 Henry K. Beecher concluded [170] that surgeons he categorized as enthusiasts relieved their patients' chest pain and heart problems more than skeptic surgeons.[15] Beginning in the 1960s, the placebo effect became widely recognized and placebo-controlled trials became the norm in the approval of new medications.[171]

Placebo-controlled studies

Main article: Placebo-controlled studies

The placebo effect makes it more difficult to evaluate new treatments. Clinical trials control for this effect by including a group of subjects that receives a sham treatment. The subjects in such trials are blinded as to whether they receive the treatment or a placebo. If a person is given a placebo under one name, and they respond, they will respond in the same way on a later occasion to that placebo under that name but not if under another.[172] Clinical trials are often double-blinded so that the researchers also do not know which test subjects are receiving the active or placebo treatment. The placebo effect in such clinical trials is weaker than in normal therapy since the subjects are not sure whether the treatment they are receiving is active.[75]

Knowingly giving a person a placebo when there is an effective treatment available is a bioethically complex issue. While placebo-controlled trials might provide information about the effectiveness of a treatment, it denies some patients what could be the best available (if unproven) treatment. Informed consent is usually required for a study to be considered ethical, including the disclosure that some test subjects will receive placebo treatments.

The ethics of placebo-controlled studies have been debated in the revision process of the Declaration of Helsinki.[173] Of particular concern has been the difference between trials comparing inert placebos with experimental treatments, versus comparing the best available treatment with an experimental treatment; and differences between trials in the sponsor's developed countries versus the trial's targeted developing countries.[174]

Nocebo

Main article: Nocebo

In the opposite effect, a patient who disbelieves in a treatment may experience a worsening of symptoms. This effect, now called by analogy nocebo (Latin nocebo = "I shall harm") can be measured in the same way as the placebo effect, e.g., when members of a control group receiving an inert substance report a worsening of symptoms. The recipients of the inert substance may nullify the placebo effect intended by simply having a negative attitude towards the effectiveness of the substance prescribed, which often leads to a nocebo effect, which is not caused by the substance, but due to other factors, such as the patient's mentality towards their ability to get well, or even purely coincidental worsening of symptoms.[79]

Placebo ingredients

Placebos used in clinical trials have sometimes had unintended consequences. A report in the Annals of Internal Medicine that looked at details from 150 clinical trials found that certain placebos used in the trials affected the results. For example, one study on cholesterol-lowering drugs used olive oil and corn oil in the placebo pills. However, according to the report, this "may lead to an understatement of drug benefit: The monounsaturated and polyunsaturated fatty acids of these 'placebos,' and their antioxidant and anti-inflammatory effects, can reduce lipid levels and heart disease." Another example researchers reported in the study was a clinical trial of a new therapy for cancer patients suffering from anorexia. The placebo that was used included lactose. However, since cancer patients typically face a higher risk of lactose intolerance, the placebo pill might actually have caused unintended side-effects that made the experimental drug look better in comparison.[175]

See also

References

  1. ^ a b Lanotte M; Lopiano; Torre; Bergamasco; Colloca; Benedetti (November 2005). "Expectation enhances autonomic responses to stimulation of the human subthalamic limbic region". Brain, Behavior, and Immunity. 19 (6): 500–9. doi:10.1016/j.bbi.2005.06.004. PMID 16055306. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  2. ^ Gensini GF, Conti AA, Conti A; Conti; Conti (April 2005). "Past and present of what will please the lord: an updated history of the concept of placebo". Minerva Medica. 96 (2): 121–4. PMID 16172581.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Harper, Douglas. "placebo". Online Etymology Dictionary.
  4. ^ placeo. Charlton T. Lewis and Charles Short. A Latin Dictionary on Perseus Project.
  5. ^ Wechsler ME, Kelley JM, Boyd IO, Dutile S, Marigowda G, Kirsch I, Israel E, Kaptchuk TJ; Kelley; Boyd; Dutile; Marigowda; Kirsch; Israel; Kaptchuk (2011). "Active albuterol or placebo, sham acupuncture, or no intervention in asthma". New England Journal of Medicine. 365 (2): 119–126. doi:10.1056/NEJMoa1103319. PMC 3154208. PMID 21751905.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b c d de Craen AJ, Kaptchuk TJ, Tijssen JG, Kleijnen J; Kaptchuk; Tijssen; Kleijnen (October 1999). "Placebos and placebo effects in medicine: historical overview". J R Soc Med. 92 (10): 511–5. PMC 1297390. PMID 10692902.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Gottlieb, Scott (18 February 2014). "The FDA Wants You for Sham Surgery". Wall Street Journal. Retrieved 8 January 2015.
  8. ^ Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, Kowalczykowski M, Miller FG, Kirsch I, Lembo AJ; Friedlander; Kelley; Sanchez; Kokkotou; Singer; Kowalczykowski; Miller; Kirsch; Lembo (2010). Boutron (ed.). "Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome". PLoS ONE. 5 (12): e15591. Bibcode:2010PLoSO...515591K. doi:10.1371/journal.pone.0015591. PMC 3008733. PMID 21203519. {{cite journal}}: Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  9. ^ Benedetti, Fabrizio; Maggi, Giuliano; Lopiano, Leonardo; Lanotte, Michele; Rainero, Innocenzo; Vighetti, Sergio; Pollo, Antonella (June 2003). "Open versus hidden medical treatments: The patient's knowledge about a therapy affects the therapy outcome". Prevention & Treatment. 6 (1). doi:10.1037/1522-3736.6.1.61a. Retrieved 13 January 2015.
  10. ^ Neurobiological Mechanisms of the Placebo Effect, Fabrizio Benedetti, Helen S. Mayberg, Tor D. Wager, Christian S. Stohler, and Jon-Kar Zubieta, The Journal of Neuroscience, 9 November 2005, 25(45) [1]
  11. ^ a b Hróbjartsson A, Norup M; Norup (June 2003). "The use of placebo interventions in medical practice--a national questionnaire survey of Danish clinicians". Evaluation & the Health Professions. 26 (2): 153–65. doi:10.1177/0163278703026002002. PMID 12789709.
  12. ^ a b Eccles R (2002). "The powerful placebo in cough studies?". Pulm Pharmacol Ther. 15 (3): 251–2. doi:10.1006/pupt.2002.0364. PMID 12099783.
  13. ^ The neural correlates of placebo effects: a disruption account, Matthew D. Lieberman, Johanna M. Jarcho, Steve Berman, Bruce D. Naliboff, Brandall Y. Suyenobu, Mark Mandelkern, and Emeran A. Mayer [2]
  14. ^ The Placebo Phenomenon, Harvard magazine, 2013
  15. ^ a b c d David H. Newman (2008). Hippocrates' Shadow. Scribner. pp. 134–59. ISBN 1-4165-5153-0.
  16. ^ a b UK Parliamentary Committee Science and Technology Committee. "Evidence Check 2: Homeopathy". Archived from the original on 2012-02-24.
  17. ^ a b Beecher HK (1955). "The powerful placebo". Journal of the American Medical Association. 159 (17): 1602–1606. doi:10.1001/jama.1955.02960340022006. PMID 13271123.
  18. ^ a b c d Hróbjartsson A, Gøtzsche PC; Gøtzsche (2001). "Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment". New England Journal of Medicine. 344 (21): 1594–1602. doi:10.1056/NEJM200105243442106. PMID 11372012.
  19. ^ a b c Moerman DE, Jonas WB; Jonas (2002). "Deconstructing the placebo effect and finding the meaning response". Ann Intern Med. 136 (6): 471–6. doi:10.7326/0003-4819-136-6-200203190-00011. PMID 11900500.
  20. ^ Hróbjartsson A, Gøtzsche PC; Gøtzsche (20 January 2010). Hróbjartsson, Asbjørn (ed.). "Placebo interventions for all clinical conditions". Cochrane Database Syst Rev. 106 (1): CD003974. doi:10.1002/14651858.CD003974.pub3. PMID 20091554.
  21. ^ a b McDonald CJ, Mazzuca SA, McCabe GP; Mazzuca; McCabe Jr (1983). "How much of the placebo 'effect' is really statistical regression?". Stat Med. 2 (4): 417–27. doi:10.1002/sim.4780020401. PMID 6369471.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Colloca L, Lopiano L, Lanotte M, Benedetti F; Lopiano; Lanotte; Benedetti (2004). "Overt versus covert treatment for pain, anxiety, and Parkinson's disease". Lancet Neurol. 3 (11): 679–84. doi:10.1016/S1474-4422(04)00908-1. PMID 15488461.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ Ernst E, Resch KL; Resch (August 1995). "Concept of true and perceived placebo effects". BMJ. 311 (7004): 551–3. doi:10.1136/bmj.311.7004.551. PMC 2550609. PMID 7663213.
  24. ^ Kienle GS, Kiene H; Kiene (December 1997). "The powerful placebo effect: fact or fiction?". J Clin Epidemiol. 50 (12): 1311–8. doi:10.1016/s0895-4356(97)00203-5. PMID 9449934.
  25. ^ Kokkotou E, Conboy LA, Ziogas DC, Quilty MT, Kelley JM, Davis RB, Lembo AJ, Kaptchuk TJ; Conboy; Ziogas; Quilty; Kelley; Davis; Lembo; Kaptchuk (2010). "Serum correlates of the placebo effect in irritable bowel syndrome". Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. 22 (3): 285–e81. doi:10.1111/j.1365-2982.2009.01440.x. PMC 2852478. PMID 20028464.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Colloca, Luana (Aug 28, 2013). Placebo and Pain: From Bench to Bedside (1st ed.). Academic Press. pp. 11–12. ISBN 9780123979315.
  27. ^ Benedetti F, Mayberg HS, Wager TD, Stohler CS, Zubieta JK; Mayberg; Wager; Stohler; Zubieta (November 2005). "Neurobiological mechanisms of the placebo effect". J. Neurosci. 25 (45): 10390–402. doi:10.1523/JNEUROSCI.3458-05.2005. PMID 16280578.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Barnett AG, van der Pols JC, Dobson AJ; Van Der Pols; Dobson (February 2005). "Regression to the mean: what it is and how to deal with it". Int J Epidemiol. 34 (1): 215–20. doi:10.1093/ije/dyh299. PMID 15333621.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Kirsch I (1985). "Response expectancy as a determinant of experience and behavior". American Psychologist. 40 (11): 1189–1202. doi:10.1037/0003-066X.40.11.1189.
  30. ^ Voudouris NJ, Peck CL, Coleman G; Peck; Coleman (1989). "Conditioned response models of placebo phenomena: further support". Pain. 38 (1): 109–16. doi:10.1016/0304-3959(89)90080-8. PMID 2780058.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Stewart-Williams S, Podd J; Podd (2004). "The placebo effect: dissolving the expectancy versus conditioning debate". Psychol Bull. 130 (2): 324–40. doi:10.1037/0033-2909.130.2.324. PMID 14979775.
  32. ^ Klinger R, Soost S, Flor H, Worm M; Soost; Flor; Worm (2007). "Classical conditioning and expectancy in placebo hypoalgesia: a randomized controlled study in patients with atopic dermatitis and persons with healthy skin". Pain. 128:31-9 (1–2): 31–9. doi:10.1016/j.pain.2006.08.025. PMID 17030095.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Colloca L, Tinazzi M, Recchia S, Le Pera D, Fiaschi A, Benedetti F, Valeriani M; Tinazzi; Recchia; Le Pera; Fiaschi; Benedetti; Valeriani (2008). "Learning potentiates neurophysiological and behavioral placebo analgesic responses". Pain. 139 (2): 306–14. doi:10.1016/j.pain.2008.04.021. PMID 18538928.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ Linde K, Witt CM, Streng A, Weidenhammer W, Wagenpfeil S, Brinkhaus B, Willich SN, Melchart D; Witt; Streng; Weidenhammer; Wagenpfeil; Brinkhaus; Willich; Melchart (2007). "The effect of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain". Pain. 128 (3): 264–71. doi:10.1016/j.pain.2006.12.006. PMID 17257756.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Bausell RB, Lao L, Bergman S, Lee WL, Berman BM; Lao; Bergman; Lee; Berman (2005). "Is acupuncture analgesia an expectancy effect? Preliminary evidence based on participants' perceived assignments in two placebo-controlled trials". Eval Health Prof. 28 (1): 9–26. doi:10.1177/0163278704273081. PMID 15677384.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  36. ^ Kirsch I (1997). "Specifying non-specifics: Psychological mechanism of the placebo effect". In Harrington A (ed.). The Placebo Effect: An Interdisciplinary Exploration. Cambridge: Harvard University Press. pp. 166–86. ISBN 978-0-674-66986-4.
  37. ^ Beedie CJ, Coleman DA, Foad AJ (2007). "Positive and negative placebo effects resulting from the deceptive administration of an ergogenic aid". Int. J. Sport Nutr. Exerc. Metab. 17: 259–269.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ Clark K, Milliken R (21 August 2000). "Today, it's "May the best swimsuit win"". US News and World Report. p. 55. Archived from the original on May 2, 2013. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help), cited in: Moerman DE, Jonas WB; Jonas (19 March 2002). "Deconstructing the placebo effect and finding the meaning response". Ann Intern Med. 136 (6): 471–6. doi:10.7326/0003-4819-136-6-200203190-00011. PMID 11900500.
  39. ^ Pollo A, Carlino E, Benedetti F; Carlino; Benedetti (July 2008). "The top-down influence of ergogenic placebos on muscle work and fatigue". Eur. J. Neurosci. 28 (2): 379–88. doi:10.1111/j.1460-9568.2008.06344.x. PMID 18702709.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  40. ^ Benedetti F, Pollo A, Colloca L; Pollo; Colloca (2007). "Opioid-mediated placebo responses boost pain endurance and physical performance – is it doping in sport competitions". J. Neurosci. 27 (44): 11934–9. doi:10.1523/JNEUROSCI.3330-07.2007. PMID 17978033.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  41. ^ de Craen AJ, Roos PJ, Leonard de Vries A, Kleijnen J; Roos; Leonard De Vries; Kleijnen (1996). "Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness". BMJ. 313 (7072): 1624–6. doi:10.1136/bmj.313.7072.1624. PMC 2359128. PMID 8991013.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Buckalew LW, Ross S; Ross (1981). "Relationship of perceptual characteristics to efficacy of placebos". Psychol. Rep. 49 (3): 955–61. doi:10.2466/pr0.1981.49.3.955. PMID 7330154.
  43. ^ Dolinska B (1999). "Empirical investigation into placebo effectiveness" (PDF). Ir J Psych Med. 16 (2): 57–58.
  44. ^ a b Geers AL, Weiland PE, Kosbab K, Landry SJ, Helfer SG; Weiland; Kosbab; Landry; Helfer (2005). "Goal activation, expectations, and the placebo effect". J Pers Soc Psychol. 89 (2): 143–59. doi:10.1037/0022-3514.89.2.143. PMID 16162050.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. ^ a b Geers AL, Helfer SG, Weiland PE, Kosbab K; Helfer; Weiland; Kosbab (2006). "Expectations and placebo response: a laboratory investigation into the role of somatic focus". J Behav Med. 29 (2): 171–8. doi:10.1007/s10865-005-9040-5. PMID 16374671.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  46. ^ a b c Moerman DE (2000). "Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure". Med Anthropol Q. 14 (51–72): 51–72. doi:10.1525/maq.2000.14.1.51. PMID 10812563.
  47. ^ Oken BS (2008). "Placebo effects: clinical aspects and neurobiology". Brain. 131 (Pt 11): 2812–23. doi:10.1093/brain/awn116. PMC 2725026. PMID 18567924.
  48. ^ a b c Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK; Stohler; Egnatuk; Wang; Koeppe; Zubieta (2008). "Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses". Arch Gen Psychiatry. 65 (2): 220–31. doi:10.1001/archgenpsychiatry.2007.34. PMID 18250260.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ Lidstone SC, Stoessl AJ (2007). "Understanding the placebo effect: contributions from neuroimaging". Mol Imaging Biol. 9 (4): 176–85. doi:10.1007/s11307-007-0086-3. PMID 17334853.
  50. ^ a b Goffaux P, Redmond WJ, Rainville P, Marchand S; Redmond; Rainville; Marchand (2007). "Descending analgesia--when the spine echoes what the brain expects". Pain. 130 (1–2): 137–43. doi:10.1016/j.pain.2006.11.011. PMID 17215080.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  51. ^ Matre D, Casey KL, Knardahl S; Casey; Knardahl (2006). "Placebo-induced changes in spinal cord pain processing". J Neurosci. 26 (2): 559–63. doi:10.1523/JNEUROSCI.4218-05.2006. PMID 16407554.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  52. ^ Qiu YH, Wu XY, Xu H, Sackett D; Wu; Xu; Sackett (October 2009). "Neuroimaging study of placebo analgesia in humans". Neuroscience Bulletin. 25 (5): 277–82. doi:10.1007/s12264-009-0907-2. PMID 19784082.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  53. ^ Zubieta JK, Stohler CS; Stohler (March 2009). "Neurobiological Mechanisms of Placebo Responses". Ann N Y Acad Sci. 1156 (1): 198–210. Bibcode:2009NYASA1156..198Z. doi:10.1111/j.1749-6632.2009.04424.x. PMC 3073412. PMID 19338509.
  54. ^ Levine JD, Gordon NC, Fields HL; Gordon; Fields (1978). "The mechanism of placebo analgesia". Lancet. 2 (8091): 654–7. doi:10.1016/s0140-6736(78)92762-9. PMID 80579.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  55. ^ de la Fuente-Fernández R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ; Ruth; Sossi; Schulzer; Calne; Stoessl (2001). "Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease". Science. 293 (5532): 1164–6. doi:10.1126/science.1060937. PMID 11498597.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  56. ^ Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S, Jerabek PA; Silva; Brannan; Tekell; Mahurin; McGinnis; Jerabek (2002). "The functional neuroanatomy of the placebo effect". Am J Psychiatry. 159 (5): 728–37. doi:10.1176/appi.ajp.159.5.728. PMID 11986125.{{cite journal}}: CS1 maint: multiple names: authors list (link)[dead link‍]
  57. ^ Leuchter AF, Cook IA, Witte EA, Morgan M, Abrams M; Cook; Witte; Morgan; Abrams (2002). "Changes in brain function of depressed subjects during treatment with placebo". Am J Psychiatry. 159 (1): 122–9. doi:10.1176/appi.ajp.159.1.122. PMID 11772700.{{cite journal}}: CS1 maint: multiple names: authors list (link)[dead link‍]
  58. ^ Kaasinen V, Aalto S, Någren K, Rinne JO; Aalto; Någren; Rinne (2004). "Expectation of caffeine induces dopaminergic responses in humans". Eur J Neurosci. 19 (8): 2352–6. doi:10.1111/j.1460-9568.2004.03310.x. PMID 15090062.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  59. ^ Haltia LT, Rinne JO, Helin S, Parkkola R, Någren K, Kaasinen V; Rinne; Helin; Parkkola; Någren; Kaasinen (2008). "Effects of intravenous placebo with glucose expectation on human basal ganglia dopaminergic function". Synapse. 62 (9): 682–8. doi:10.1002/syn.20541. PMID 18566972.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  60. ^ Volkow ND, Wang GJ, Ma Y, Fowler JS, Wong C, Jayne M, Telang F, Swanson JM; Wang; Ma; Fowler; Wong; Jayne; Telang; Swanson (2006). "Effects of expectation on the brain metabolic responses to methylphenidate and to its placebo in non-drug abusing subjects". NeuroImage. 32 (4): 1782–92. doi:10.1016/j.neuroimage.2006.04.192. PMID 16757181.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  61. ^ Faria V, Fredrikson M, Furmark T; Fredrikson; Furmark (2008). "Imaging the placebo response: a neurofunctional review". Eur Neuropsychopharmacol. 18 (7): 473–85. doi:10.1016/j.euroneuro.2008.03.002. PMID 18495442.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  62. ^ Diederich NJ, Goetz CG; Goetz (2008). "The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies". Neurology. 71 (9): 677–84. doi:10.1212/01.wnl.0000324635.49971.3d. PMID 18725593.
  63. ^ Ader R, Cohen N; Cohen (1975). "Behaviorally conditioned immunosuppression". Psychosom Med. 37 (4): 333–40. doi:10.1097/00006842-197507000-00007. PMID 1162023.
  64. ^ a b Pacheco-López G, Engler H, Niemi MB, Schedlowski M; Engler; Niemi; Schedlowski (2006). "Expectations and associations that heal: Immunomodulatory placebo effects and its neurobiology". Brain Behav Immun. 20 (430–46): 430–46. doi:10.1016/j.bbi.2006.05.003. PMID 16887325.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  65. ^ Colloca L, Benedetti F; Benedetti (2005). "Placebos and painkillers: is mind as real as matter?". Nat Rev Neurosci. 6 (7): 545–52. doi:10.1038/nrn1705. PMID 15995725.
  66. ^ Eippert F, Finsterbusch J, Bingel U, Büchel C; Finsterbusch; Bingel; Büchel (2009). "Direct evidence for spinal cord involvement in placebo analgesia". Science. 326 (5951): 404. Bibcode:2009Sci...326..404E. doi:10.1126/science.1180142. PMID 19833962.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  67. ^ Murray, D; Stoessl, AJ (December 2013). "Mechanisms and therapeutic implications of the placebo effect in neurological and psychiatric conditions". Pharmacology & therapeutics. 140 (3): 306–18. doi:10.1016/j.pharmthera.2013.07.009. PMID 23880289.
  68. ^ Humphrey N (2002). "Great Expectations: The Evolutionary Psychology of Faith-Healing and the Placebo Effect". The Mind Made Flesh: Essays from the Frontiers of Psychology and Evolution (PDF). Oxford University Press. pp. 255–85. ISBN 978-0-19-280227-9.
  69. ^ Hróbjartsson A, Gøtzsche PC; Gøtzsche (2004). "Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment". J. Intern. Med. 256 (2): 91–100. doi:10.1111/j.1365-2796.2004.01355.x. PMID 15257721.
  70. ^ Wampold BE, Minami T, Tierney SC, Baskin TW, Bhati KS; Minami; Tierney; Baskin; Bhati (2005). "The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials". J Clin Psychol. 61 (7): 835–54. doi:10.1002/jclp.20129. PMID 15827993.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  71. ^ Wampold BE, Imel ZE, Minami T; Imel; Minami (2007). "The placebo effect: "relatively large" and "robust" enough to survive another assault". J Clin Psychol. 63 (4): 401–3. doi:10.1002/jclp.20350. PMID 17279522.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  72. ^ Hróbjartsson A, Gøtzsche PC; Gøtzsche (2007). "Powerful spin in the conclusion of Wampold et al.'s re-analysis of placebo versus no-treatment trials despite similar results as in original review". J Clin Psychol. 63 (4): 373–7. doi:10.1002/jclp.20357. PMID 17279532.
  73. ^ Hunsley J, Westmacott R; Westmacott (2007). "Interpreting the magnitude of the placebo effect: mountain or Molehill?". J Clin Psychol. 63 (4): 391–9. doi:10.1002/jclp.20352. PMID 17279525.
  74. ^ Meissner K, Distel H, Mitzdorf U; Distel; Mitzdorf (2007). "Evidence for placebo effects on physical but not on biochemical outcome parameters: a review of clinical trials". BMC Med. 5 (1): 3. doi:10.1186/1741-7015-5-3. PMC 1847831. PMID 17371590. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  75. ^ a b Vase L, Riley JL, Price DD; Riley Jl; Price (2003). "A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia". Pain. 99 (3): 714–5. doi:10.1016/S0304-3959(02)00205-1. PMID 12406519.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  76. ^ Barfod TS (2005). "Placebos in medicine: Placebo use is well known, placebo effect is not". BMJ. 330 (7481): 45. doi:10.1136/bmj.330.7481.45. PMC 539859. PMID 15626818.
  77. ^ Hróbjartsson A, Gøtzsche PC; Gøtzsche (January 2010). Hróbjartsson, Asbjørn (ed.). "Placebo interventions for all clinical conditions". Cochrane Database of Systematic Reviews (1): CD003974. doi:10.1002/14651858.CD003974.pub3. PMID 20091554.
  78. ^ Howick J, Friedemann C, Tsakok M, Watson R, Tsakok T, Thomas J, Perera R, Fleming S, Heneghan C; Friedemann; Tsakok; Watson; Tsakok; Thomas; Perera; Fleming; Heneghan (May 2013). "Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis". PLOS ONE. 5. 8 (5): e62599. Bibcode:2013PLoSO...862599H. doi:10.1371/journal.pone.0062599. PMC 3655171. PMID 23690944. Retrieved 28 June 2013.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  79. ^ a b "The Nocebo Effect". Priory.com. 10 February 2007. Retrieved 2009-07-08.
  80. ^ Shapiro AK, Chassan J, Morris LA, Frick R (1974). "Placebo induced side effects". Journal of Operational Psychiatry. 6: 43–6.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  81. ^ Benedetti F, Amanzio M, Baldi S, Casadio C, Cavallo A, Mancuso M, Ruffini E, Oliaro A, Maggi G; Amanzio; Baldi; Casadio; Cavallo; Mancuso; Ruffini; Oliaro; Maggi (1998). "The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression". Pain. 75 (2–3): 313–9. doi:10.1016/S0304-3959(98)00010-4. PMID 9583767.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  82. ^ Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S, Manson JE, Barnabei VM, Lane DS, Brzyski RG, Rosal MC, Wylie-Rosett J, Hays J; Barad; Cochrane; Larson; Gass; Wassertheil-Smoller; Manson; Barnabei; Lane; Brzyski; Rosal; Wylie-Rosett; Hays (2005). "Symptom experience after discontinuing use of estrogen plus progestin". JAMA. 294 (2): 183–93. doi:10.1001/jama.294.2.183. PMID 16014592.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  83. ^ Chua, Shunjie (2015). "The Ethics of Prescription of Placebos to Patients with Major Depressive Disorder". Chinese Medical Journal. 128: 1555. doi:10.4103/0366-6999.157699. Retrieved 28 May 2015.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  84. ^ Nitzan U, Lichtenberg P; Lichtenberg (October 23, 2004). "Questionnaire survey on use of placebo". BMJ. 329 (7472): 944–6. doi:10.1136/bmj.38236.646678.55. PMC 524103. PMID 15377572.
  85. ^ a b Spiegel D (October 23, 2004). "Placebos in practice: Doctors use them, they work in some conditions, but we don't know how they work". BMJ. 329 (7472): 927–8. doi:10.1136/bmj.329.7472.927. PMC 524090. PMID 15499085.
  86. ^ Sandler AD, Bodfish JW; Bodfish (2008). "Open-label use of placebos in the treatment of ADHD: a pilot study". Child Care Health Dev. 34 (1): 104–10. doi:10.1111/j.1365-2214.2007.00797.x. PMID 18171451.
  87. ^ Altunç U, Pittler MH, Ernst E; Pittler; Ernst (2007). "Homeopathy for childhood and adolescence ailments: Systematic review of randomized clinical trials". Mayo Clinic proceedings. Mayo Clinic. 82 (1): 69–75. doi:10.4065/82.1.69. PMID 17285788.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  88. ^ Doctors Struggle With Tougher-Than-Ever Dilemmas: Other Ethical Issues Author: Leslie Kane. 11/11/2010
  89. ^ Rutherford, Bret R.; Pott, Emily; Tandler, Jane M.; Wall, Melanie M.; Roose, Steven P.; Lieberman, Jeffrey A. (8 October 2014). "Placebo Response in Antipsychotic Clinical Trials". JAMA Psychiatry. 71 (12): 1409–21. doi:10.1001/jamapsychiatry.2014.1319. PMID 25321611.
  90. ^ Tuttle, AH; Tohyama, S; Ramsay, T; Kimmelman, J; Schweinhardt, P; Bennett, GJ; Mogil, JS (22 August 2015). "Increasing placebo responses over time in U.S. clinical trials of neuropathic pain". Pain. 156: 2616–26. doi:10.1097/j.pain.0000000000000333. PMID 26307858. {{cite journal}}: Unknown parameter |lay-url= ignored (help)
  91. ^ Benedetti F (1996). "The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia". Pain. 64 (3): 535–43. doi:10.1016/0304-3959(95)00179-4. PMID 8783319.
  92. ^ Levine JD, Gordon NC, Bornstein JC, Fields HL; Gordon; Bornstein; Fields (1979). "Role of pain in placebo analgesia". Proc Natl Acad Sci U S A. 76 (7): 3528–31. Bibcode:1979PNAS...76.3528L. doi:10.1073/pnas.76.7.3528. PMC 383861. PMID 291020.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  93. ^ Finniss, Damien G; Kaptchuk, Ted J; Miller, Franklin; Benedetti, Fabrizio (February 2010). "Biological, clinical, and ethical advances of placebo effects". The Lancet. 375 (9715): 686–695. doi:10.1016/S0140-6736(09)61706-2. PMC 2832199. PMID 20171404.
  94. ^ Doongaji DR, Vahia VN, Bharucha MP; Vahia; Bharucha (1978). "On placebos, placebo responses and placebo responders. (A review of psychological, psychopharmacological and psychophysiological factors)". Journal of Postgraduate Medicine. 24 (2): 91–7. PMID 364041.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  95. ^ a b Hoffman GA, Harrington A, Fields HL; Harrington; Fields (2005). "Pain and the placebo: what we have learned". Perspect Biol Med. 48 (2): 248–65. doi:10.1353/pbm.2005.0054. PMID 15834197.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  96. ^ Zubieta JK, Yau WY, Scott DJ, Stohler CS; Yau; Scott; Stohler (2006). "Belief or Need? Accounting for individual variations in the neurochemistry of the placebo effect". Brain Behav Immun. 20 (1): 15–26. doi:10.1016/j.bbi.2005.08.006. PMID 16242910.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  97. ^ Benedetti F, Arduino C, Costa S, Vighetti S, Tarenzi L, Rainero I, Asteggiano G; Arduino; Costa; Vighetti; Tarenzi; Rainero; Asteggiano (2006). "Loss of expectation-related mechanisms in Alzheimer's disease makes analgesic therapies less effective". Pain. 121 (1–2): 133–44. doi:10.1016/j.pain.2005.12.016. PMID 16473462.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  98. ^ Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P; Cucherat; Arzimanoglou; Ryvlin (August 12, 2008). Klassen, Terry (ed.). "Greater Response to Placebo in Children Than in Adults: A Systematic Review and Meta-Analysis in Drug-Resistant Partial Epilepsy". PLoS Med. 5 (8): e166. doi:10.1371/journal.pmed.0050166. PMC 2504483. PMID 18700812.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  99. ^ Furmark T, Appel L, Henningsson S, Ahs F, Faria V, Linnman C, Pissiota A, Frans O, Bani M, Bettica P, Pich EM, Jacobsson E, Wahlstedt K, Oreland L, Långström B, Eriksson E, Fredrikson M; Appel; Henningsson; Ahs; Faria; Linnman; Pissiota; Frans; Bani; Bettica; Pich; Jacobsson; Wahlstedt; Oreland; Långström; Eriksson; Fredrikson (December 2008). "A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety". J. Neurosci. 28 (49): 13066–74. doi:10.1523/JNEUROSCI.2534-08.2008. PMID 19052197.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  100. ^ "The Placebo Effect: Not All in Your Head", ScienceNOW Daily News, 2 December 2008 Archived 2009-01-23 at the Wayback Machine
  101. ^ "First 'placebo gene' discovered", New Scientist, 03 December 2008
  102. ^ Tirrell, Meg (24 October 2012). "Genetics May Help Explain Placebo Effect, Researchers Say". Bloomberg L.P. Retrieved 1 November 2012.
  103. ^ Hall KT, Lembo AJ, Kirsch I, Ziogas DC, Douaiher J, Jensen KB, Conboy LA, Kelley JM, Kokkotou E, Kaptchuk TJ; Lembo; Kirsch; Ziogas; Douaiher; Jensen; Conboy; Kelley; Kokkotou; Kaptchuk (2012). "Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome". PLoS ONE. 7 (10): e48135. Bibcode:2012PLoSO...748135H. doi:10.1371/journal.pone.0048135. PMC 3479140. PMID 23110189.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  104. ^ Evans, Dylan (2003). Placebo: the belief effect. London: HarperCollins. ISBN 0-00-712612-3.
  105. ^ Cousins, Norman (1989). Head First. New York: E. P. Dutton. pp. 229–231.
  106. ^ Placebo Effect. Cancer.org. Retrieved on 2013-08-25.
  107. ^ Price, DD; Finniss, DG; Benedetti, F (2008). "A comprehensive review of the placebo effect: recent advances and current thought". Annual Review of Psychology. 59 (1): 565–90. doi:10.1146/annurev.psych.59.113006.095941. PMID 17550344.
  108. ^ Puhl, AA; Reinhart, CJ; Rok, ER; Injeyan, HS (2011). "An examination of the observed placebo effect associated with the treatment of low back pain - a systematic review". Pain Research & Management. 16 (1): 45–52. PMID 21369541.
  109. ^ Kirsch I., Deacon B., Huedo-Medina T., Scoboria A., Moore T., Johnson B. (2008). "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration". PLoS Med. 5 (2): e45. doi:10.1371/journal.pmed.0050045. PMC 2253608. PMID 18303940.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  110. ^ Turner, E. H; Rosenthal, R. (2008). "Efficacy of antidepressants". BMJ. 336 (7643): 516–517. doi:10.1136/bmj.39510.531597.80. ISSN 0959-8138. PMC 2265347. PMID 18319297.
  111. ^ Fountoulakis, Konstantinos N.; Möller, Hans-Jürgen (2010). "Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data". The International Journal of Neuropsychopharmacology. 14 (03): 405–412. doi:10.1017/S1461145710000957. ISSN 1461-1457. PMID 20800012.
  112. ^ Khan A, Redding N, Brown WA (2008). "The persistence of the placebo response in antidepressant clinical trials". Journal of Psychiatric Research. 42 (10): 791–796. doi:10.1016/j.jpsychires.2007.10.004. PMID 18036616.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  113. ^ Rief, Winfried; Nestoriuc, Yvonne; Weiss, Sarah; Welzel, Eva; Barsky, Arthur J.; Hofmann, Stefan G. (November 2009). "Meta-analysis of the placebo response in antidepressant trials". Journal of Affective Disorders. 118 (1–3): 1–8. doi:10.1016/j.jad.2009.01.029. PMID 19246102.
  114. ^ Asai A., Kadooka Y. (2013). "Reexamination of the ethics of placebo use in clinical practice". Bioethics. 27 (4): 186–193. doi:10.1111/j.1467-8519.2011.01943.x.
  115. ^ Michels (2000). "The Placebo Problem Remains". Arch Gen Psychiatry. 57 (4): 321–322. doi:10.1001/archpsyc.57.4.321.
  116. ^ Cho HJ, Hotopf M, Wessely S; Hotopf; Wessely (2005). "The placebo response in the treatment of chronic fatigue syndrome: A systematic review and meta-analysis" (PDF). Psychosom Med. 67 (2): 301–13. doi:10.1097/01.psy.0000156969.76986.e0. PMID 15784798. Retrieved 2008-12-12.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  117. ^ Schweizer E, Rickels K; Rickels (1997). "Placebo response in generalized anxiety: its effect on the outcome of clinical trials". J Clin Psychiatry. 58 (Suppl 11): 30–8. PMID 9363046.
  118. ^ Piercy MA, Sramek JJ, Kurtz NM, Cutler NR; Sramek; Kurtz; Cutler (1996). "Placebo response in anxiety disorders". Ann Pharmacother. 30 (9): 1013–9. PMID 8876864.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  119. ^ Kemeny ME, Rosenwasser LJ, Panettieri RA, Rose RM, Berg-Smith SM, Kline JN; Rosenwasser; Panettieri; Rose; Berg-Smith; Kline (2007). "Placebo response in asthma: a robust and objective phenomenon". J Allergy Clin Immunol. 119 (6): 1375–81. doi:10.1016/j.jaci.2007.03.016. PMID 17451796.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  120. ^ Kaptchuk TJ, Kelley JM, Deykin A, Wayne PM, Lasagna LC, Epstein IO, Kirsch I, Wechsler ME; Kelley; Deykin; Wayne; Lasagna; Epstein; Kirsch; Wechsler (2008). "Do "placebo responders" exist?". Contemp Clin Trials. 29 (4): 587–95. doi:10.1016/j.cct.2008.02.002. PMID 18378192.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  121. ^ Sandler A (2005). "Placebo effects in developmental disabilities: implications for research and practice". Ment Retard Dev Disabil Res Rev. 11 (2): 164–70. doi:10.1002/mrdd.20065. PMID 15977316.
  122. ^ Sandler AD, Sutton KA, DeWeese J, Girardi MA, Sheppard V, Bodfish JW; Sutton; Deweese; Girardi; Sheppard; Bodfish (1999). "Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder" (PDF). N Engl J Med. 341 (24): 1801–6. doi:10.1056/NEJM199912093412404. PMID 10588965.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  123. ^ Madersbacher S, Marszalek M, Lackner J, Berger P, Schatzl G; Marszalek; Lackner; Berger; Schatzl (2007). "The long-term outcome of medical therapy for BPH". Eur Urol. 51 (6): 1522–33. doi:10.1016/j.eururo.2007.03.034. PMID 17416456.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  124. ^ Bulik CM, Brownley KA, Shapiro JR; Brownley; Shapiro (2007). "Diagnosis and management of binge eating disorder". World Psychiatry. 6 (3): 142–8. PMC 2174583. PMID 18188431.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  125. ^ Sysko R, Walsh BT; Walsh (2007). "A systematic review of placebo response in studies of bipolar mania". J Clin Psychiatry. 68 (8): 1213–7. doi:10.4088/JCP.v68n0807. PMID 17854245.
  126. ^ Kuten-Shorrer, M; Kelley, JM; Sonis, ST; Treister, NS (April 2014). "Placebo effect in burning mouth syndrome: a systematic review". Oral diseases. 20 (3): e1–6. doi:10.1111/odi.12192. PMID 24164777.
  127. ^ Su C, Lichtenstein GR, Krok K, Brensinger CM, Lewis JD; Lichtenstein; Krok; Brensinger; Lewis (2004). "A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease". Gastroenterology. 126 (5): 1257–69. doi:10.1053/j.gastro.2004.01.024. PMID 15131785.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  128. ^ Kirsch, I. Sapirstein, G. (1998) Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention & Treatment. 1, ArtID 2a abstract
  129. ^ Walsh, BT; Seidman, SN; Sysko, R; Gould, M (10 April 2002). "Placebo response in studies of major depression: variable, substantial, and growing". JAMA. 287 (14): 1840–7. doi:10.1001/jama.287.14.1840. PMID 11939870.
  130. ^ Andrews G (2001). "Placebo response in depression: bane of research, boon to therapy". Br J Psychiatry. 178 (3): 192–4. doi:10.1192/bjp.178.3.192. PMID 11230026.
  131. ^ Moncrieff J, Wessely S, Hardy R; Wessely; Hardy (2004). Moncrieff, Joanna (ed.). "Active placebos versus antidepressants for depression". Cochrane Database Syst Rev (1): CD003012. doi:10.1002/14651858.CD003012.pub2. PMID 14974002. CD003012.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  132. ^ Mearin F, Balboa A, Zárate N, Cucala M, Malagelada JR; Balboa; Zárate; Cucala; Malagelada (1999). "Placebo in functional dyspepsia: symptomatic, gastrointestinal motor, and gastric sensorial responses". Am J Gastroenterol. 94 (1): 116–25. doi:10.1111/j.1572-0241.1999.00781.x. PMID 9934741.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  133. ^ Niklson I, Edrich P, Verdru P; Edrich; Verdru (2006). "Identifying baseline characteristics of placebo responders versus nonresponders in randomized double-blind trials of refractory partial-onset seizures". Epileptic Disord. 8 (1): 37–44. PMID 16567324.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  134. ^ Kriston L, Harms A, Berner MM; Harms; Berner (2006). "A meta-regression analysis of treatment effect modifiers in trials with flexible-dose oral sildenafil for erectile dysfunction in broad-spectrum populations". Int J Impot Res. 18 (6): 559–65. doi:10.1038/sj.ijir.3901479. PMID 16688210.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  135. ^ Moerman, Daniel E. (2002). Meaning, Medicine and the Placebo Effect. Cambridge University Press. ISBN 978-0521000871. ISBN 0-521-80630-5 (10).
  136. ^ Diener HC, Schorn CF, Bingel U, Dodick DW; Schorn; Bingel; Dodick (2008). "The importance of placebo in headache research". Cephalagia. 28 (10): 1003–11. doi:10.1111/j.1468-2982.2008.01660.x. PMID 18727647.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  137. ^ Archer TP, Leier CV; Leier (1992). "Placebo treatment in congestive heart failure". Cardiology. 81 (2–3): 125–33. doi:10.1159/000175787. PMID 1286471.
  138. ^ Curie, A; Yang, K; Kirsch, I; Gollub, RL; des Portes, V; Kaptchuk, TJ; Jensen, KB (2015). "Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis". PLOS ONE. 10 (7): e0133316. doi:10.1371/journal.pone.0133316. PMID 26226597.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  139. ^ van Laarhoven, AI; van der Sman-Mauriks, IM; Donders, AR; Pronk, MC; van de Kerkhof, PC; Evers, AW (1 December 2014). "Placebo Effects on Itch: A Meta-Analysis of Clinical Trials of Patients with Dermatological Conditions". J Invest Dermatol. doi:10.1038/jid.2014.522. PMID 25609025.
  140. ^ Patel SM, Stason WB, Legedza A, Ock SM, Kaptchuk TJ, Conboy L, Canenguez K, Park JK, Kelly E, Jacobson E, Kerr CE, Lembo AJ; Stason; Legedza; Ock; Kaptchuk; Conboy; Canenguez; Park; Kelly; Jacobson; Kerr; Lembo (2005). "The placebo effect in irritable bowel syndrome trials: a meta-analysis". Neurogastroenterol Motil. 17 (3): 332–40. doi:10.1111/j.1365-2982.2005.00650.x. PMID 15916620.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  141. ^ Pitz M, Cheang M, Bernstein CN; Cheang; Bernstein (2005). "Defining the predictors of the placebo response in irritable bowel syndrome". Clin Gastroenterol Hepatol. 3 (237–47): 237–47. doi:10.1016/S1542-3565(04)00626-3. PMID 15765443.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  142. ^ van Leeuwen, JH; Castro, R; Busse, M; Bemelmans, BL (September 2006). "The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms". European Urology. 50 (3): 440–52, discussion 453. doi:10.1016/j.eururo.2006.05.014. PMID 16753253.
  143. ^ Macedo A, Baños JE, Farré M; Baños; Farré (2008). "Placebo response in the prophylaxis of migraine: a meta-analysis". Eur J Pain. 12 (1): 68–75. doi:10.1016/j.ejpain.2007.03.002. PMID 17451980.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  144. ^ Meissner, K; Fässler, M; Rücker, G; Kleijnen, J; Hróbjartsson, A; Schneider, A; Antes, G; Linde, K (25 November 2013). "Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis". JAMA internal medicine. 173 (21): 1941–51. doi:10.1001/jamainternmed.2013.10391. PMID 24126676.
  145. ^ La Mantia L, Eoli M, Salmaggi A, Milanese C; Eoli; Salmaggi; Milanese (1996). "Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature". The Italian Journal of Neurological Sciences. 17 (2): 135–9. doi:10.1007/BF02000844. PMID 8797067.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  146. ^ Wolf S (1950). "Effects of suggestion and conditioning on the action of chemical agents in human subjects—the pharmacology of placebos". J Clin Invest. 29 (1): 100–9. doi:10.1172/JCI102225. PMC 439730. PMID 15399519.
  147. ^ Zhang Z, Wang Y, Wang Y, Xu F; Wang; Wang; Xu (2008). "Antiemetic placebo: reduce adverse drug interactions between chemotherapeutic agents and antiemetic drugs in cancer patients". Med Hypotheses. 70 (3): 551–5. doi:10.1016/j.mehy.2007.06.029. PMID 17703892.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  148. ^ Shiao SY, Dune LS; Dune (2006). "Metaanalyses of acustimulations: effects on nausea and vomiting in postoperative adult patients". Explore (NY). 2 (3): 202–15. doi:10.1016/j.explore.2006.02.005. PMID 16781643.
  149. ^ Zhang, W; Robertson, J; Jones, A C; Dieppe, P A; Doherty, M (1 December 2008). "The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials". Annals of the Rheumatic Diseases. 67 (12): 1716–1723. doi:10.1136/ard.2008.092015. PMID 18541604.
  150. ^ Bannuru, RR; McAlindon, TE; Sullivan, MC; Wong, JB; Kent, DM; Schmid, CH (28 July 2015). "Effectiveness and Implications of Alternative Placebo Treatments: A Systematic Review and Network Meta-Analysis of Osteoarthritis Trials". Annals of Internal Medicine. 163: 365–72. doi:10.7326/M15-0623. PMID 26215539.
  151. ^ Lee, S; Malhotra, B; Creanga, D; Carlsson, M; Glue, P (22 July 2009). "A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder". BMC medical research methodology. 9: 55. doi:10.1186/1471-2288-9-55. PMID 19624824.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  152. ^ Mangera, A; Chapple, CR; Kopp, ZS; Plested, M (5 July 2011). "The placebo effect in overactive bladder syndrome". Nat Rev Urol. 8 (9): 495–503. doi:10.1038/nrurol.2011.99. PMID 21727941.
  153. ^ Baker B, Khaykin Y, Devins G, Dorian P, Shapiro C, Newman D; Khaykin; Devins; Dorian; Shapiro; Newman (2003). "Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect". Can J Psychiatry. 48 (6): 381–7. PMID 12894612.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  154. ^ de la Fuente-Fernández R, Stoessl AJ; Stoessl (2002). "The placebo effect in Parkinson's disease". Trends Neurosci. 25 (6): 302–6. doi:10.1016/S0166-2236(02)02181-1. PMID 12086748.
  155. ^ Goetz CG, Wuu J, McDermott MP, Adler CH, Fahn S, Freed CR, Hauser RA, Olanow WC, Shoulson I, Tandon PK, Leurgans S; Wuu; McDermott; Adler; Fahn; Freed; Hauser; Olanow; Shoulson; Tandon; Parkinson Study; Leurgans (2008). "Placebo response in Parkinson's disease: comparisons among 11 trials covering medical and surgical interventions". Mov Disord. 23 (5): 690–9. doi:10.1002/mds.21894. PMID 18228568.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  156. ^ Brockbank J, Gladman D; Gladman (2002). "Diagnosis and management of psoriatic arthritis". Drugs. 62 (17): 2447–57. doi:10.2165/00003495-200262170-00004. PMID 12421102.
  157. ^ Pace F, Maconi G, Molteni P, Minguzzi M, Bianchi Porro G; MacOni; Molteni; Minguzzi; Bianchi Porro (1995). "Meta-analysis of the effect of placebo on the outcome of medically treated reflux esophagitis". Scand J Gastroenterol. 30 (2): 101–5. doi:10.3109/00365529509093245. PMID 7732329.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  158. ^ Fulda S, Wetter TC; Wetter (2008). "Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies". Brain. 131 (Pt 4): 902–17. doi:10.1093/brain/awm244. PMID 17932100.
  159. ^ Pollo A, Benedetti F; Benedetti (2008). "Placebo response: relevance to the rheumatic diseases". Rheum Dis Clin North Am. 34 (2): 331–49. doi:10.1016/j.rdc.2008.04.002. PMID 18638680.
  160. ^ Bradford A, Meston C; Meston (2007). "Correlates of Placebo Response in the Treatment of Sexual Dysfunction in Women: A Preliminary Report". J Sex Med. 4 (5): 1345–51. doi:10.1111/j.1743-6109.2007.00578.x. PMC 2859204. PMID 17666035.
  161. ^ Oosterbaan DB, van Balkom AJ, Spinhoven P, van Dyck R; Van Balkom; Spinhoven; Van Dyck (2001). "The placebo response in social phobia". J Psychopharmacol. 15 (3): 199–203. doi:10.1177/026988110101500314. PMID 11565629.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  162. ^ Ilnyckyj A, Shanahan F, Anton PA, Cheang M, Bernstein CN; Shanahan; Anton; Cheang; Bernstein (1997). "Quantification of the placebo response in ulcerative colitis". Gastroenterology. 112 (6): 1854–8. doi:10.1053/gast.1997.v112.pm9178676. PMID 9178676.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  163. ^ Jacobs B (2000). "Biblical origins of placebo". J R Soc Med. 93 (4): 213–4. PMC 1297986. PMID 10844895.
  164. ^ Shapiro AK (1968). "Semantics of the placebo". Psychiatr Q. 42 (4): 653–95. doi:10.1007/BF01564309. PMID 4891851.
  165. ^ Kaptchuk TJ (1998). "Powerful placebo: the dark side of the randomised controlled trial". Lancet. 351 (9117): 1722–5. doi:10.1016/S0140-6736(97)10111-8. PMID 9734904.
  166. ^ Booth C (2005). "The rod of Aesculapios: John Haygarth (1740-1827) and Perkins' metallic tractors". Journal of medical biography. 13 (3): 155–161. doi:10.1258/j.jmb.2005.04-01. PMID 16059528.
  167. ^ Haygarth, J., Of the Imagination, as a Cause and as a Cure of Disorders of the Body; Exemplified by Fictitious Tractors, and Epidemical Convulsions , Crutwell, (Bath), 1800.
  168. ^ T. C. Graves (1920). "Commentary on a case of Hystero-epilepsy with delayed puberty". The Lancet. 196 (5075): 1135. doi:10.1016/S0140-6736(01)00108-8. Retrieved January 2, 2014.
  169. ^ Michael D. Yapko (2012). Trancework: An Introduction to the Practice of Clinical Hypnosis. Routledge. p. 123. ISBN 9780415884945.
  170. ^ Beecher HK (July 1961). "Surgery as placebo. A quantitative study of bias". J Am Med Assoc. 176 (13): 1102–7. doi:10.1001/jama.1961.63040260007008. PMID 13688614.
  171. ^ Kaptchuk TJ (1998). "Intentional ignorance: a history of blind assessment and placebo controls in medicine". Bulletin of the History of Medicine. 72 (3): 389–433. doi:10.1353/bhm.1998.0159. PMID 9780448.
  172. ^ Whalley B, Hyland ME, Kirsch I; Hyland; Kirsch (2008). "Consistency of the placebo effect". Journal of Psychosomatic Research. 64 (5): 537–41. doi:10.1016/j.jpsychores.2007.11.007. PMID 18440407.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  173. ^ Howick J (25 Aug 2009). "Questioning the Methodologic Superiority of 'Placebo' over 'Active' Controlled Trials". Am J Bioeth. 9 (9): 34–48. doi:10.1080/15265160903090041. PMID 19998192.
  174. ^ Kottow M (21 July 2010). "The improper use of research placebos". Journal of Evaluation in Clinical Practice. 16 (6): 1041–4. doi:10.1111/j.1365-2753.2009.01246.x. PMID 20663001.
  175. ^ Golomb BA, Erickson LC, Koperski S, Sack D, Enkin M, Howick J; Erickson; Koperski; Sack; Enkin; Howick (2010). "What's in placebos: who knows? Analysis of randomized, controlled trials". Ann Intern Med. 153 (8): 532–5. doi:10.1059/0003-4819-153-8-201010190-00010. PMID 20956710. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: multiple names: authors list (link)
Look up placebo in Wiktionary, the free dictionary.
Wikiquote has quotations related to Placebo effect.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Placebo&oldid=708302132"