|
A placebo
is a sham medical intervention. In one common placebo procedure, a patient is given an inert sugar pill
, told that it may improve his/her condition, but not told that it is in fact inert. Such an intervention may cause the patient to believe the treatment will change his/her condition; and this belief does indeed sometimes have a therapeutic effect, causing the patient's condition to improve. This phenomenon is known as the placebo effect
.
Placebos are widely used in medicine, and the placebo effect is a pervasive phenomenon; [1] in fact, it is part of the response to any active medication.[ However, the deceptive nature of the placebo creates tension between the Hippocratic Oath and the honesty of the doctor-patient relationship.][ The placebo effect points to the importance of perception and the brain's role in physical health.
]
Since the publication of Henry K. Beecher's The Powerful Placebo
in 1955 the phenomenon has been considered to have clinically important effects.[ 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.][ The article received a flurry of criticism,][ but the authors later published a Cochrane review with similar conclusions. [2] Most studies have attributed the difference from baseline till 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.][
]
|
PLACEBO TICKETS
|
Definitions, effects, and ethics
A placebo has been defined as "a substance or procedure ... that is objectively without specific activity for the condition being treated". [ Under this definition, a wide variety of things can be placebos and exhibit a placebo effect. Pharmacological substances administered through any means can act as placebos, including pills, creams, inhalants, and injections. Medical devices such as ultrasound can act as placebos. [3] [4] Sham surgery, [5] [6] [7] sham electrodes implanted in the brain,] and sham acupuncture, either with sham needles or on fake acupuncture points, have all exhibited placebo effects. [8] Bedding not treated to reduce allergies has been used as a placebo to control for treated bedding. [9] The physician has even been called a placebo; [10]pp. 33–34 a study found that patient recovery can be increased by words that suggest the patient “would be better in a few days”, and if the patient is given treatment, that “the treatment would certainly make him better” rather than negative words such as “"I am not sure that the treatment I am going to give you will have an effect". [11] 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 (in the latter case no more so than saline) 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. [12]
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 which does not directly cause anything. [13] Instead they introduced the word "meaning response" for the meaning 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.][ 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. [14]
]
The placebo effect has been controversial throughout history. Notable medical organizations have endorsed it,[ 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]
]
History
The word placebo, Latin for "I shall please", dates back to a Latin translation of the Bible by Jerome. [16] It was first used in a medicinal context in the 18th century. In 1785 it was defined as a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit the patient", sometimes with a derogative implication [17] but not with the implication of no effect. [18] Placebos were widespread in medicine until the 20th century, and they were sometimes endorsed as necessary deceptions. [19] In 1903 Richard Cabot said that he was brought up to use placebos,[ 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".][ In 1961 Henry Beecher found [20] that patients of surgeons he categorized as enthusiasts relieved their patients' chest pain and heart problems more than skeptic surgeons.][ In 1961 Walter Kennedy introduced the word nocebo.][
]
Mechanism of the effect
When an inert substance makes a patient better, that effect is called the placebo effect. The phenomenon is related to the perception and expectation which the patient has; 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. Placebo effects are a scientific mystery. [21] Their basic mechanism has been investigated since 1978, when it was found that the opioid antagonist naloxone could block placebo painkillers, suggesting that endogenous opioids are involved. [22]
Expectancy and conditioning
Placebos exert an "expectancy" effect whereby an inert substance which is believed to be a drug has effects similar to the actual drug. Placebos can act similarly through classical conditioning, where a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus. [23] Both conditioning and expectations play a role in placebo effect, [24] and make different kinds of contribution. Conditioning has a longer lasting effect, [25] and can effect earlier stages of information processing. [26] A conditioned pain reduction can be totally removed when its existence is explained. [27] The expectancy effect can be enhanced through factors such as the enthusiasm of the doctor, differences in size and color of placebo pills, or the use of other inventions such as injections. In one study, the response to a placebo increased from 44% to 62% when the doctor gave them with "warmth, attention, and confidence". [28] Expectancy effects have been found to occur with a range of substances. Those who think a treatment will work display a stronger placebo effect than those who do not, as evidenced by a study of acupuncture. [29] [30]
Because the placebo effect is based upon expectations and conditioning, the effect disappears if the patient is told that their expectations are unrealistic, or that the placebo intervention is ineffective. A conditioned pain reduction can be totally removed when its existence is explained. It has also been reported of subjects given placebos in a trial of anti-depressants, that “Once the trial was over and the patients who had been given placebos were told as much, they quickly deteriorated.” [31]
A placebo described as a muscle relaxant will cause muscle relaxation and if described as the opposite, muscle tension. [32] 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. [33] The consumption of caffeine has been reported to cause similar effects even when decaffeinated coffee is consumed, although a 2003 study found only limited support for this. [34] Alcohol placebos can cause intoxication [35] and sensimotor impairment. [36] Perceived ergogenic substances can increase endurance [37] and weight-lifting ability, [38] leading to the question of whether placebos should be allowed in sport competition. [39] Placebos can help smokers quit. [40] Perceived allergens which are not truly allergenic can cause allergies. [41] Inventions such as psychotherapy can have placebo effects.pp 164–173 Swimsuits have even been thought to increase swimmer speed. [42] The effect has been observed in the transplantation of human embryonic neurons into the brains of those with advanced Parkinson's disease. [43]
Because placebos are dependent upon perception and expectation, various factors which 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. [44] One researcher has found that big pills increase the effect [45] while another has argued that the effect is dependent upon cultural background. [46] More pills, [47] branding, [48] past experience, [49] and high price [50] increase the effect of placebo pills. Injection [51] and acupuncture have larger effect than pills. Proper adherence to placebos have been found to decrease mortality. [52]
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. [53] [54] 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 upon the placebo treatment of gastric and duodenal ulcers shows that this varies widely with society: those in Germany having a high rate placebo effect while those in Brazil a low one. Placebo effects in treating gastric ulcers is low in Brazil, higher in northern Europe (Denmark, Netherlands) and extremely high in Germany. But the placebo effect for hypertension is lower in Germany than elsewhere [55] Social observation can induce a placebo effect such when a person sees another having reduced pain following what they believe is a pain reducing procedure. [56]
The placebo effect can work selectively. If an analgesic placebo cream is applied on one hand, it will reduce pain only in that hand and not elsewhere on the body [57] 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. [58]
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, [59] [60] [61] and the spinal cord. [62] [63] These changes can act upon the brain’s early stages of information processing: research using evoked brain potentials upon painful laser pulses, for example, finds placebo effects upon the N2–P2, a biphasic negative–positive complex response, the N2 peak of which is at about 230 ms, and the P2 one at about 380 ms. They occur not only during placebo analgesia but after receiving the analgesic placebo (the areas are different here, and involve the medial prefrontal cortex, posterior parietal cortex and inferior parietal lobule). [64]
Different areas in the higher brain have different functions. The prefrontal involvement could be related to recalling the placebo and maintaining its cognitive presence in a “self-reinforcing feedback loop” (during pain an individual recalls having taken the placebo and reduced pain reinforces its status as an analgesic). [65] The rostral anterior cingulate cortex and its subcortical connectivity could be related to the expectation of potential pain stimuli [66] [67]
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 conversely, anti-analgesic nocebos responses were associated with deactivation in this part of the brain of dopamine and opioid release. (It has been known that placebo analgesia depends upon the release in the brain of endogenous opioids since 1978. [68]) Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray on spinal nociceptive reflexes, while the expectations of anti-analgesic nocebos acts in the opposite way to block this.
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. [69]
- Depression: Placebos reducing depression affect many of the same areas that are activated by antidepressants with the addition of the prefrontal cortex [70] [71]
- Caffeine: placebo caffeinated coffee causes an increase in bilateral dopamine release in the thalamus. [72]
- Glucose: the expectation of an intravenous injection of glucose increases the release of dopamine in the basal ganglia of men (but not women). [73]
- 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. [74]
Present 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”. [75] And “Diseases lacking major “top-down” or cortically based regulation may be less
prone to placebo-related improvement”. [76]
Brain and body
The brain has control over the body processes affected by placebos. Pain, motor fatigue and fever are directly organized by the brain. Other processes usually regulated by the body such as the immune system are also controlled indirectly through the sympathetic and parasympathetic nervous system.
Research upon conditioning in animals shows the brain can learn control over them. 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 that causes immunosuppression. After learning this pairing, the taste of saccharin by itself through neural top down control created immunosuppression, as a new conditioned response. [77] Such conditioning has been found to effect a diverse variety of basic physiological processes not just in the immune system but ones such as serum iron levels, oxidative DNA damage levels, and insulin secretion. This work was originally done on rats, however, the same conditioning of basic physiological processes can also occur in humans. Recent reviews have argued the placebo effect is due to top down control by the brain for immunity [78] and pain. [79] 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.”pp 441
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. [80]
Clinical utility
Duration
Placebo effects can last for a long time: over 8 weeks for panic disorder, [81]
6 months for angina pectoris, [82] and two and half years for rheumatoid arthritis. [83] Placebo effects after verbal suggestion for mild pain can be robust and still exist after being repeated 10 times even if they have no actual pharmacological pain killing action
Clinical significance
Hróbjartsson and Peter Gøtzsche published a study in 2001 [84] and a follow-up study in 2004 [85] questioning the nature of the placebo effect. The studies were performed as two meta-analyses involving all published 156 clinical trials in which an experimental drug or treatment protocol was compared to a placebo group and an untreated group, and specifically asked whether the placebo group improved compared to the untreated group. Hróbjartsson and Gøtzsche 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. Similarly, 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 only be documented 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 have argued 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 ameneable to the placebo effect. [86] [87]
Hróbjartsson and Gøtzsche's conclusion has been criticised on several grounds. Their meta-analysis covered studies into a highly mixed group of conditions: the placebo effect does occur with peripheral disease processes (such as Hypertension, asthma, prostatic hyperplasia, anal fissure, bronchitis) though not for processes reflecting physical disease (such as venous leg ulcers, Crohn’s disease, urinary tract infection chronic heart failure. [88] 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. [89] Other writers have argued that the placebo effect can be reliably demonstrated under appropriate conditions. [90]
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. [91]
Another negative consequence is that placebos can cause side-effects associated with real treatment. [92] 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. [93]
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 40.5% of those on placebo compared to 63.3% of those on hormone replacement. [94]
Doctor-patient relationship
A study of Danish general practitioners found that 48% had prescribed a placebo at least 10 times in the past year. The most frequently prescribed placebos were 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. [95] The accompanying editorial concluded, "We cannot afford to dispense with any treatment that works, even if we are not certain how it does." [96] Other researches 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. [97]
Critics of the practice responded that it is unethical to prescribe treatments that don't work, and that telling a patient 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.
The following impracticalities exist with placebos (see the BMJ posted responses to Spiegel's editorial .
- Roughly only 30% of the population seems susceptible to placebo effects, and it is not possible to determine ahead of time whether a placebo will work or not.
- All placebo effects eventually wear off, thus making the placebo effect impractical for long term or chronic medical matters.
- Patients rightfully want immediate relief or improvement from their illness or symptoms. A non-placebo can often provide that, while a placebo might not.
- Legitimate doctors and pharmacists could open themselves up to charges of fraud since sugar pills would cost pennies or cents for a bottle, but the price for a "real" medication would have to be charged to avoid making the patient suspicious.
- Unscrupulous medical practitioners could swindle patients with fake surgeries and sugar pills, then later claim that they only meant to help their patients by using "placebos".
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. 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 can not 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.
The individual
Who is affected
Placebos do not work upon everyone. [98] [99] Henry K. Beecher, in a paper in 1955 [100] suggested placebo effects occurred to about 35% of people. However, the response rate is wide from 0% up to nearly everyone. In a dental postoperative pain model, analgesia occurred in 39%. Research upon ischemic arm pain, placebo analgesia was found in 27%. The analgesia for cutaneous heating of left hand skin was 56%. [101]
Though not everyone responds to a placebo, neither does everyone respond to an active drug, the percentage of patients who reported relief following placebo (39%) is similar to the percentage following 4 mg
(36%) and 6 mg (50%) of hidden morphine. [102]
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 [103] and it now thought to have no effect. [104]
The desire for relief from pain, “goal motivation”, and how far pain is expected to be relieved increases placebo analgesia. Another factor increasing the effectiveness of placebos is the degree to which a person attends to their symptoms, “somatic focus”. Individual variation in response to analgesic placebos has been linked to regional neurochemical differences in the internal affective state of the individuals experiencing pain. [105]
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. [106]
Children seem to have greater response than adults to placebos. [107]
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. [108] [109] [110]
The authors note "additional work is necessary to elucidate the generalizability of the findings".
Symptoms and conditions
The placebo effect occurs more strongly in some conditions than others. One study found placebo effects are most likely to be found with the peripheral aspects of disease processes (such as hypertension, asthma, prostatic hyperplasia, anal fissure, bronchitis) rather than processes that reflect physical disease (such as venous leg ulcers, Crohn’s disease, urinary tract infection, and chronic heart failure.) Dylan Evans has suggested another factor 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. [111]
There has been research upon the placebo effect in a number of conditions.
Pain
Placebo analgesia is more likely to work the more severe the pain [112] It can be effective: one study found for postoperative pain following the extraction of the third molar, that a saline injected while telling the patient it was a powerful painkiller was as potent as a 6–8 mg dose of morphine.
Most research reports average reduction for a group of people, and this is lower (some people do not respond).
In one study using injection of capsaicin below the skin found that this reduced group average pain compared to no placebo by ~46% to ~57%. Another measure is the ability to endure pain. In one study, placebos increased this on average by about 3.5 minutes in the context of just under 14 minutes without it. [113] The average strength of placebos upon pain on a visual analog scale is 2 out of 10 units [114] Individuals that respond to placebos show greater effects and can be 5 out of 10 units.
Depression
A meta-analysis in 1998 found that 75% of the effectiveness of anti-depressant medication is due to the placebo-effect rather than the treatment itself. [115] A meta-analysis in 2008 found that 79% of depressed patients receiving placebo remained well compared to 93% of those receiving antidepressants for the effect of placebos (for 12 weeks after an initial 6–8 weeks of successful therapy). [116] Another meta-analysis in 2002 found a 30% reduction in suicide and attempted suicide in the placebo groups compared to a 40% reduction in the treated groups. [117]
A 2002 article in The Washington Post titled "Against Depression, a Sugar Pill Is Hard to Beat" summarized research as follows, "in the majority of trials conducted by drug companies in recent decades, sugar pills have done as well as -- or better than -- antidepressants. Companies have had to conduct numerous trials to get two that show a positive result, which is the Food and Drug Administration's minimum for approval. the makers of Prozac had to run five trials to obtain two that were positive, and the makers of Paxil and Zoloft had to run even more”.
Gastric and duodenal ulcers
A meta-study of 31 placebo-controlled trials of the gastric acid secretion inhibitor drug Cimetidine in the treatment of gastric or duodenal ulcers found that placebo treatments, in many cases, were as effective as active drugs: of the 1692 patients treated in the 31 trials, 76% of the 916 treated with the drug were "healed", and 48% of the 776 treated with placebo were "healed". [118] (It is now known gastic secretion is irrelevant since most ulcers are due to the bacterium Helicobacter pylori).) These results were confirmed by the direct post-treatment endoscopy. It was also found that German placebos were "stronger" than others; and that, overall, different physicians evoked quite different placebo responses in the same clinical trial (p. 15). Moreover, that in many of these trials the gap between the active drugs and the placebo controls was "not because [the trials' constituents] had high drug effectiveness, but because they had low placebo effectiveness" (p. 13).
In some trials, placebos were effective in 90% of the cases, whilst in others the placebos were only effective in 10% of the cases. It was argued that "what is demonstrated in [these] studies is not enhanced healing in drug groups, but reduced healing in placebo groups" (p. 14). It was also noted the results of two studies (one conducted in Germany, the other in Denmark), which examined "ulcer relapse in healed patients" showed that the rate of relapse amongst those "healed" by the active drug treatment was five times
that of those "healed" by the placebo treatment (pp. 14–15).
List of medical conditions
The placebo is an inert pill unless otherwise stated
- ADHD:adult, [119] child
- Amalgam fillings: attributed symptoms (inert "chelation" therapy) [120]
- Anxiety disorders [121] [122]
- Asthma (water aerosol inhalant) [123]
- Asthma [124] [125]table 1
- Autism: language and behavior problems [126] [127]
- Benign prostatic enlargement [128]
- Binge eating disorder [129]
- Bipolar mania [130]
- Cough [131]
- Crohn's disease [132]
- Depression (Light treatment; low red light placebo) [133]
- Depression
[134] [135] [136]
- Dyspepsia and gastric motility [137]
|
- Epilepsy [138]
- Erectile dysfunction [139]
- Food allergy: ability to eat ill-making foods
p. 54
- Gastric and duodenal ulcers
[140]
- Headache [141]
- Heart failure, congestive [142]
- Herpes simplex [143]
- Hypertension: mild and moderate
[144]
- Irritable bowel syndrome [145] [146]
- Migraine prophylaxis [147]
- Multiple sclerosis [148]
- Nausea: gastric activity [149]
- Nausea: chemotherapy [150]
- Nausea and vomiting: postoperative (sham acupuncture) [151]
|
- Pain
[152]
- Panic disorders [153]
- Parkinson’s disease [154] [155]
- Pathological gambling [156]
- Premenstrual dysphoric disorder. [157]
- Psoriatic arthritis [158]
- Reflux esophagitis [159]
- Restless leg syndrome [160]
- Rheumatic diseases [161]
- Sexual dysfunction: women [162]
- Social phobia [163]
- Third molar extraction swelling (sham ultra-sound)
- Ulcerative colitis [164]
- Vulvar vestibulitis [165]
|
Placebo-controlled studies
The placebo effect makes it more difficult to evaluate new treatments. Apparent benefits of a new treatment (usually a drug but not necessarily so) may not derive from the treatment but from the placebo effect. This is particularly likely given that new therapies seem to have greater placebo effects. 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. Often clinical trials are double blinded so that the researchers also do not know which 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.
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 violates the rights of that person to receive the best available treatment. This issue is covered by the Declaration of Helsinki.
Nocebo
In the opposite effect, a patient who disbelieves in a treatment may experience a worsening of symptoms. This effect, now called by analogy the "nocebo effect" (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 his or her ability to get well, or even purely coincidental worsening of symptoms.
See also
}}|placebo}}
in Wiktionary, the free dictionary.
}}
- Adverse effect (medicine)
- Autosuggestion
- Belief
- Charm
- Confounding factor
- Culture-specific syndrome
- Efficacy
- Expectation
- Hawthorne effect
- Homeopathy
- Hypnotic susceptibility
- Iatrogenesis
- Intention
- Medication
- Nocebo
- Observer-expectancy effect
- Optimism
- Pessimism
- Pharmacology
- Post hoc ergo propter hoc
- Psychiatry
- Psychosomatic illness
- Pygmalion effect
- Self-fulfilling prophecy
- Simulation
- Subject-expectancy effect
- Therapeutic effect
- Thomas theorem
- Unintended consequence
References
- Hróbjartsson A, Norup M. 2003 The use of placebo interventions in medical practice--a national questionnaire survey of Danish clinicians. Eval Health Prof. Jun;26(2):153-65. {{PMID|12789709}}
- Placebo interventions for all clinical conditions
- Ho KH, Hashish I, Salmon P, Freeman R, Harvey W. (1988) Reduction of post-operative swelling by a placebo effect. J Psychosom Res. 32:197-205. {{PMID|3404502}}
- Hashish I, Harvey W, Harris M. (1986) Anti-inflammatory effects of ultrasound therapy: evidence for a major placebo effect. Br J Rheumatol. 25:77-81.{{PMID|2417648}}
- Cobb LA, Thomas GI, Dillard DH, Merendino KA, Bruce RA. (1959) An evaluation of internal-mammary-artery ligation by a double-blind technic. N Engl J Med. 260:1115-8. {{PMID|13657350}}
- Benson H, McCallie DP Jr. (1979) Angina pectoris and the placebo effect. N Engl J Med. 300:1424-9. {{PMID|35750}}
- Moseley JB, O'Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, Hollingsworth JC, Ashton CM, Wray NP. (2002) A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 347:81-8. {{PMID|12110735}}
- Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH. (2006) Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ. 332:391-7. {{PMID|16452103}}
- Holm L, Bengtsson A, van Hage-Hamsten M, Ohman S, Scheynius A. (2001) Effectiveness of occlusive bedding in the treatment of atopic dermatitis--a placebo-controlled trial of 12 months' duration. Allergy. 56:152-8. {{PMID|11167376}}
- Margo CE. (1999) The placebo effect. Surv Ophthalmol. 44:31-44. {{PMID|10466586}}
- Thomas KB. (1987) General practice consultations: is there any point in being positive? Br Med J (Clin Res Ed). 294:1200-2. {{PMID|3109581}}
- Colloca L, Lopiano L, Lanotte M, Benedetti F. (2004) Overt versus covert treatment for pain, anxiety, and Parkinson's disease. Lancet Neurol. 3:679-84.{{PMID|15488461}}
- Moerman DE, Jonas WB. (2002) Deconstructing the placebo effect and finding the meaning response. Ann Intern Med. 136:471-6. {{PMID|11900500}}
- Concept of true and perceived placebo effects
- Hippocrates' Shadow
- Jacobs B. (2000) Biblical origins of placebo. J R Soc Med. 93(4):213-4. {{PMID|10844895}}
- Shapiro AK. (1968) Semantics of the placebo. Psychiatr Q. 42:653-95. {{PMID|4891851}}
- Kaptchuk TJ. (1998) Powerful placebo: the dark side of the randomised controlled trial. Lancet. 351(9117):1722-5.{{PMID|9734904}}
- Placebos and placebo effects in medicine: historical overview
- Surgery as placebo. A quantitative study of bias
- Eccles R, Eccles, K.S.J. Placebo effect (2007) Encyclopedia of life sciences . John Wiley & Sons {{doi|10.1038/npg.els.0004114}} ISBN 978-0470066515
- Neurobiological mechanisms of the placebo effect
- Voudouris NJ, Peck CL, Coleman G. (1989) Conditioned response models of placebo phenomena: further support. Pain. 38:109-16.{{PMID|2780058}}
- Stewart-Williams S, Podd J. (2004) The placebo effect: dissolving the expectancy versus conditioning debate. Psychol Bull. 130:324-40. {{PMID|14979775}}
- Klinger R, Soost S, Flor H, Worm M. (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.{{PMID|17030095}}
- Colloca L, Tinazzi M, Recchia S, Le Pera D, Fiaschi A, Benedetti F, Valeriani M. (2008) Pain. Learning potentiates neurophysiological and behavioral placebo analgesic responses 139:306-14. {{PMID|18538928}}
- Montgomery GH, Kirsch I. (1997) Classical conditioning and the placebo effect. Pain. 72:107-13. {{PMID|9272794}}
- Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, Kirsch I, Schyner RN, Nam BH, Nguyen LT, Park M, Rivers AL, McManus C, Kokkotou E, Drossman DA, Goldman P, Lembo AJ. (2008) Components of placebo effect: randomized controlled trial in patients with irritable bowel syndrome. BMJ. 336(7651):999-1003. {{PMID|18390493}}
- Linde K, Witt CM, Streng A, Weidenhammer W, Wagenpfeil S, Brinkhaus B, Willich SN, Melchart D. (2007) The effect of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain. Pain. 128:264-71. {{PMID|17257756}}
- Bausell RB, Lao L, Bergman S, Lee WL, Berman BM. (2005) Is acupuncture analgesia an expectancy effect? Preliminary evidence based on participants' perceived assignments in two placebo-controlled trials. Eval Health Prof. 28:9-26. {{PMID|15677384}}
- Against Depression, a Sugar Pill Is Hard to Beat, The Washington Post, May 7, 2002
- Flaten MA, Simonsen T, Olsen H. (1999) Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom Med. 61:250-5.{{PMID|10204979}}
- 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 166–186. ISBN 978-0674669864
- Flaten MA, Aasli O, Blumenthal TD. (2003) Expectations and placebo responses to caffeine-associated stimuli. Psychopharmacology 169:198-204. {{PMID|12759808}}
- O'Boyle DJ, Binns AS, Sumner JJ. (1994) On the efficacy of alcohol placebos in inducing feelings of intoxication. Psychopharmacology (Berl). 115:229-36. {{PMID|7862899}}
- Fillmore MT, Mulvihill LE, Vogel-Sprott M. (1994) The expected drug and its expected effect interact to determine placebo responses to alcohol and caffeine. Psychopharmacology 115:383-8. {{PMID|7871080}}
- Beedie, C.J., Coleman, D.A. & Foad, A.J. (2007) Positive and negative placebo effects resulting from the deceptive administration of an ergogenic aid. Int. J. Sport Nutr. Exerc. Metab., 17, 259–269
- The top-down influence of ergogenic placebos on muscle work and fatigue
- Benedetti, F., Pollo, A. & Colloca, L. (2007) Opioid-mediated placebo responses boost pain endurance and physical performance – is it doping in sport competitions? J. Neurosci., 27, 11934–11939.
- Dar R, Stronguin F, Etter JF. (2005) Assigned versus perceived placebo effects in nicotine replacement therapy for smoking reduction in Swiss smokers. J Consult Clin Psychol. 73:350-3.{{PMID|15796644}}
- Ikemi, Y., Nakagawa. S. (1962) A psychosomatic study of contagious der matitis. Kyoshu Journal of Medical Science, 13: 335-350
- Clark K, Milliken R. “Today, it’s “May the best swimsuit win.”” US News and World Report. 21 August 2000:55. Cited by: Moerman DE, Jonas WB. (2002) Deconstructing the placebo effect and finding the meaning response. Ann Intern Med. 136:471-6. {{PMID|11900500}}
- McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, Ellgring JH, Fahn S, Greene P, Dillon S, Winfield H, Bjugstad KB, Freed CR. (2004) Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry. 61:412-20. {{PMID|15066900}}
- de Craen AJ, Roos PJ, Leonard de Vries A, Kleijnen J. (1996) Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness. BMJ. 313:1624-6. {{PMID|8991013}}
- Buckalew LW, Ross S. (1981) Relationship of perceptual characteristics to efficacy of placebos. Psychol Rep. 49:955-61. {{PMID|7330154}}
- Empirical investigation into placebo effectiveness
- Blackwell B, Bloomfield SS, Buncher CR. (1972) Demonstration to medical students of placebo responses and non-drug factors. Lancet. 1(7763):1279-82. {{PMID|4113531}}
- Branthwaite A, Cooper P. (1981) Analgesic effects of branding in treatment of headaches. Br Med J (Clin Res Ed). 282:1576-8.{{PMID|6786566}}
- Colloca L, Benedetti F. (2006) How prior experience shapes placebo analgesia. Pain. 124:126-33. {{PMID|16701952}}
- Waber RL, Shiv B, Carmon Z, Ariely D. (2008) Commercial features of placebo and therapeutic efficacy. JAMA.;299(9):1016-7. {{PMID|18319411}}
- Grenfell RF, Briggs AH, Holland WC. (1961) A double-blind study of the treatment of hypertension. JAMA. 176:124-8. {{PMID|13708477}}
- Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, Johnson JA. (2006) A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 333(7557):15. {{PMID|16790458}}
- Geers AL, Weiland PE, Kosbab K, Landry SJ, Helfer SG. (2005) Goal activation, expectations, and the placebo effect. J Pers Soc Psychol. 89:143-59. {{PMID|16162050}}
- Geers AL, Helfer SG, Weiland PE, Kosbab K. (2006) Expectations and placebo response: a laboratory investigation into the role of somatic focus. J Behav Med. 29:171-8. {{PMID|16374671}}
- Moerman DE. (2000) Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure. Med Anthropol Q. 14:51-72.{{PMID|10812563}}
- Colloca L, Benedetti F. (2009). Placebo analgesia induced by social observational learning. Pain. 144(1-2):28-34. {{doi|10.1016/j.pain.2009.01.033}} PMID 19278785
- Benedetti F, Arduino C, Amanzio M. (1999) Somatotopic activation of opioid systems by target-directed expectations of analgesia. J Neurosci. 19:3639-48.{{PMID|10212322}}
- Whalley B, Hyland ME, Kirsch I. (2008) Consistency of the placebo effect. J Psychosom Res. 64(5):537-41. {{PMID|18440407}}
- Oken BS. (2008) Placebo effects: clinical aspects and neurobiology. Brain. 131:2812-23. {{PMID|18567924}}
- Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK. (2008) Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry. 65:220-31. {{PMID|18250260}}
- Lidstone SC, Stoessl AJ. (2007) Understanding the placebo effect: contributions from neuroimaging. Mol Imaging Biol. 9:176-85. {{PMID|17334853}}
- Goffaux P, Redmond WJ, Rainville P, Marchand S. (2007) Descending analgesia--when the spine echoes what the brain expects. Pain. 130:137-43. {{PMID|17215080}}
- Matre D, Casey KL, Knardahl S. (2006) Placebo-induced changes in spinal cord pain processing. J Neurosci. 26:559-63.{{PMID|16407554}}
- Nemoto H, Nemoto Y, Toda H, Mikuni M, Fukuyama H. (2007) Placebo analgesia: a PET study. Exp Brain Res. 179:655-64. {{PMID|17287994}}
- Craggs JG, Price DD, Verne GN, Perlstein WM, Robinson MM. (2007) Functional brain interactions that serve cognitive-affective processing during pain and placebo analgesia. Neuroimage. 38:720-9. {{PMID|17904390}}
- Bingel U, Lorenz J, Schoell E, Weiller C, Büchel C. (2006) Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network. Pain. 120:8-15. {{PMID|16364549}}
- Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, Kosslyn SM, Rose RM, Cohen JD. (2004) Placebo-induced changes in FMRI in the anticipation and experience of pain. Science. 303:1162-7. {{PMID|14976306}}
- Levine JD, Gordon NC, Fields HL. (1978) The mechanism of placebo analgesia. Lancet. 2(8091):654-7. {{PMID|80579 }}
- de la Fuente-Fernández R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ. (2001) Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science. 293:1164-6. {{PMID|11498597}}
- Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S, Jerabek PA. (2002) The functional neuroanatomy of the placebo effect. Am J Psychiatry. 159:728-37. {{PMID|11986125}}
- Leuchter AF, Cook IA, Witte EA, Morgan M, Abrams M. (2002) Changes in brain function of depressed subjects during treatment with placebo. Am J Psychiatry. 159:122-9. {{PMID|11772700}}
- Kaasinen V, Aalto S, Någren K, Rinne JO. (2004) Expectation of caffeine induces dopaminergic responses in humans. Eur J Neurosci. 19(8):2352-6. {{PMID|15090062}}
- Haltia LT, Rinne JO, Helin S, Parkkola R, Någren K, Kaasinen V. (2008) Effects of intravenous placebo with glucose expectation on human basal ganglia dopaminergic function. Synapse. 62(9):682-8. {{PMID|18566972}}
- Volkow ND, Wang GJ, Ma Y, Fowler JS, Wong C, Jayne M, Telang F, Swanson JM. (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.{{PMID|16757181}}
- Faria V, Fredrikson M, Furmark T. (2008) Imaging the placebo response: a neurofunctional review. Eur Neuropsychopharmacol. 18(7):473-85. {{PMID|18495442}}
- Diederich NJ, Goetz CG. (2008) The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies. Neurology. 71:677-84. {{PMID|18725593}}
- Ader, R. Cohen, N. (1975) "Behaviorally conditioned immunosuppression". Psychosom Med. 37: 333-340 {{PMID|1162023}}
- Pacheco-López G, Engler H, Niemi MB, Schedlowski M. (2006) Expectations and associations that heal: Immunomodulatory placebo effects and its neurobiology. Brain Behav Immun. 20:430-46. {{PMID|16887325}}
- Colloca L, Benedetti F. (2005) Placebos and painkillers: is mind as real as matter? Nat Rev Neurosci. 6:545-52. {{PMID|15995725}}
- Humphrey, Nicholas. (2002) "Great Expectations: The Evolutionary Psychology of Faith-Healing and the Placebo Effect", in ''The Mind Made Flesh: Essays from the Frontiers of Psychology and Evolution'', chapter 19, pages 255-85, Oxford University Press ISBN 978-0192802279
- Coryell W, Noyes R. (1988) Placebo response in panic disorder. Am J Psychiatry. 145:1138-40.{{PMID|3046384}}
- Boissel JP, Philippon AM, Gauthier E, Schbath J, Destors JM. (1986) Time course of long-term placebo therapy effects in angina pectoris. Eur Heart J. 7:1030-6. {{PMID|3104043}}
- Traut EF, Passarelli EW. (1957) Placebos in the treatment of rheumatoid arthritis and other rheumatic conditions. Ann Rheum Dis. 16:18-22. {{PMID|13412002}}
- Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment
- Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment
- Wampold BE, Minami T, Tierney SC, Baskin TW, Bhati KS. (2005) The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials. J Clin Psychol. 61:835-54.{{PMID|15827993}}
- Wampold BE, Imel ZE, Minami T. (2007) The placebo effect: "relatively large" and "robust" enough to survive another assault. J Clin Psychol. 63(4):401-3{{PMID|17279522}}
- Meissner K, Distel H, Mitzdorf U. (2007) Evidence for placebo effects on physical but not on biochemical outcome parameters: a review of clinical trials. BMC Med. 5:3. {{PMID|17371590}}
- Vase L, Riley JL 3rd, Price DD. (2003) Pain. 104:714-5 A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia.{{PMID|12406519}}
- Barfod TS. 2005. Placebos in medicine: placebo use is well known, placebo effect is not. ''BMJ.'' 330:45. {{PMID|15626818}}
- The Nocebo Effect
- Shapiro, A. K., Chassan, J., Morris, L. A., & Frick, R. (1974) Placebo induced side effects. Journal of Operational Psychiatry, 6:43–46. abstract
- Benedetti F, Amanzio M, Baldi S, Casadio C, Cavallo A, Mancuso M, Ruffini E, Oliaro A, Maggi G. (1998) The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression. Pain. 75:313-9. {{PMID|9583767}}
- 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. (2005) Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 294:183-93. {{PMID|16014592}}
- Nitzan U, Lichtenberg P. 2004 Questionnaire survey on use of placebo. BMJ. Oct 23;329(7472):944-6. {{PMID|15377572}}
- Spiegel D. Placebos in practice. 2004 BMJ. Oct 23;329(7472):927-8. {{PMID|15499085}}
- Sandler AD, Bodfish JW. (2008) Open-label use of placebos in the treatment of ADHD: a pilot study. Child Care Health Dev. 34:104-10. {{PMID|18171451}}
- Benedetti F. (1996) The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia. Pain. 64:535-43. {{PMID|8783319}}
- Levine JD, Gordon NC, Bornstein JC, Fields HL. (1979) http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=383861&blobtype=pdf of pain in placebo analgesia. Proc Natl Acad Sci U S A. 76:3528-31. {{PMID|291020}}
- Beecher HK. (1955) The powerful placebo. J Am Med Assoc. 159(17):1602-6. {{PMID|13271123}}
- Petrovic P, Kalso E, Petersson KM, Ingvar M. (2002) Placebo and opioid analgesia-- imaging a shared neuronal network. Science. 295:1737-40. {{PMID|11834781}} (see Supplementary Material)
- Levine JD, Gordon NC, Smith R, Fields HL. (1981) Analgesic responses to morphine and placebo in individuals with postoperative pain. Pain. 10:379-89. {{PMID|7279424}}
- Doongaji DR, Vahia VN, Bharucha MP. (1978) On placebos, placebo responses and placebo responders. (A review of psychological, psychopharmacological and psychophysiological factors). I. Psychological factors. J Postgrad Med. 24:91-7.{{PMID|364041}}
- Hoffman GA, Harrington A, Fields HL. (2005) Pain and the placebo: what we have learned. Perspect Biol Med. 48:248-65.{{PMID|15834197}}
- Zubieta JK, Yau WY, Scott DJ, Stohler CS. (2006) Belief or Need? Accounting for individual variations in the neurochemistry of the placebo effect. Brain Behav Immun. 20:15-26.{{PMID|16242910}}>
- Benedetti F, Arduino C, Costa S, Vighetti S, Tarenzi L, Rainero I, Asteggiano G. (2006) of expectation-related mechanisms in Alzheimer's disease makes analgesic therapies less effective. Pain. 121:133-44.{{PMID|16473462}}
- Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P. (2008) Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med. Aug 12;5(8):e166. {{PMID|18700812}}
- A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety
- "The Placebo Effect: Not All in Your Head", ScienceNOW Daily News, 2 December 2008
- "First 'placebo gene' discovered", ''New Scientist'', 03 December 2008
- Evens, D. (2003) Placebo: The belief effect. HarperCollins ISBN 978-0007126125
- Levine JD, Gordon NC, Bornstein JC, Fields HL. (1979) Role of pain in placebo analgesia. Proc Natl Acad Sci U S A. 76:3528-31.{{PMID|291020}}
- Amanzio M, Benedetti F. (1999) Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci. 19:484-94. {{PMID|9870976}}
- Levine JD, Gordon NC. (1984) Influence of the method of drug administration on analgesic response. Nature. 312(5996):755-6. {{PMID|6514008}}
- Kirsch, I. Sapirstein, G. (1998) Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention & Treatment. 1, ArtID 2a abstract
- Khan A et al. (2008). The persistence of the placebo response in antidepressant clinical trials. ''Journal of Psychiatric Research '''42'''(10):791-796.
- Khan A, Warner HA, and Brown WA. 2000. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database. ''Arch Gen Psychiatry'' 57:311–317. {{PMID|10768687}}
- Meaning, Medicine and the Placebo Effect
- Levin FR, Evans SM, Brooks DJ, Kalbag AS, Garawi F, Nunes EV. (2006) Treatment of methadone-maintained patients with adult ADHD: double-blind comparison of methylphenidate, bupropion and placebo. Drug Alcohol Depend. 81:137-48. {{PMID|16102908}}
- Grandjean P, Guldager B, Larsen IB, Jørgensen PJ, Holmstrup P. (1997) Placebo response in environmental disease. Chelation therapy of patients with symptoms attributed to amalgam fillings. J Occup Environ Med. 39:707-14. {{PMID|9273873}}
- Schweizer E, Rickels K. (1997) Placebo response in generalized anxiety: its effect on the outcome of clinical trials. J Clin Psychiatry. 58 Suppl 11:30-8. {{PMID|9363046}}
- Piercy MA, Sramek JJ, Kurtz NM, Cutler NR. (1996) Placebo response in anxiety disorders. Ann Pharmacother. 30:1013-9. {{PMID|8876864}}
- Butler C, Steptoe A. (1986) Placebo responses: an experimental study of psychophysiological processes in asthmatic volunteers. Br J Clin Psychol. 25:173-83. {{PMID|3768575}}
- Kemeny ME, Rosenwasser LJ, Panettieri RA, Rose RM, Berg-Smith SM, Kline JN. (2007) Placebo response in asthma: a robust and objective phenomenon. J Allergy Clin Immunol. 119:1375-81. {{PMID|17451796}}
- Kaptchuk TJ, Kelley JM, Deykin A, Wayne PM, Lasagna LC, Epstein IO, Kirsch I, Wechsler ME. (2008) Do "placebo responders" exist? Contemp Clin Trials. 29:587-95. {{PMID|18378192}}
- Sandler A. (2005) Placebo effects in developmental disabilities: implications for research and practice. Ment Retard Dev Disabil Res Rev.;11:164-70. {{PMID|15977316}}
- Sandler AD, Sutton KA, DeWeese J, Girardi MA, Sheppard V, Bodfish JW. (1999) Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. N Engl J Med. 341:1801-6.{{PMID|10588965}}
- Madersbacher S, Marszalek M, Lackner J, Berger P, Schatzl G. (2007) The long-term outcome of medical therapy for BPH.Eur Urol. 51:1522-33. {{PMID|17416456}}
- Bulik CM, Brownley KA, Shapiro JR. (2007) Diagnosis and management of binge eating disorder. World Psychiatry. 6:142-8. {{PMID|18188431}}
- Sysko R, Walsh BT. (2007) A systematic review of placebo response in studies of bipolar mania. J Clin Psychiatry. 68:1213-7. {{PMID|17854245}}
- Eccles R. (2002) The powerful placebo in cough studies? Pulm Pharmacol Ther. 15:251-2. {{PMID|12099783}}
- Su C, Lichtenstein GR, Krok K, Brensinger CM, Lewis JD. (2004) A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease. Gastroenterology. 126:1257-69. {{PMID|15131785}}
- Loving RT, Kripke DF, Elliott JA, Knickerbocker NC, Grandner MA. (2005) Bright light treatment of depression for older adults (ISRCTN55452501). BMC Psychiatry. 5:41. {{PMID|16283925}}
- Egbert LD, Battit GE, Welch CE, Bartlett MK. (1964) Reduction of postoperative pain by encouragement and instruction of patients. A study of doctor-patient rapport. N Engl J Med. 270:825-7.{{PMID|14108087}}
- Andrews G. (2001) Placebo response in depression: bane of research, boon to therapy. Br J Psychiatry. 178:192-4. {{PMID|11230026}}
- Moncrieff J, Wessely S, Hardy R. (2004) Active placebos versus antidepressants for depression. Cochrane Database Syst Rev. (1):CD003012. {{PMID|14974002}}
- Mearin F, Balboa A, Zárate N, Cucala M, Malagelada JR. (1999) Placebo in functional dyspepsia: symptomatic, gastrointestinal motor, and gastric sensorial responses. Am J Gastroenterol. 94:116-25. {{PMID|9934741}}
- Niklson I, Edrich P, Verdru P. (2006) Identifying baseline characteristics of placebo responders versus nonresponders in randomized double-blind trials of refractory partial-onset seizures. Epileptic Disord. 8:37-44. {{PMID|16567324}}
- Kriston L, Harms A, Berner MM. (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. 18:559-65. {{PMID|16688210}}
- Moerman D. E. (2000) Cultural Variations in the Placebo Effect: Ulcers, Anxiety, and Blood Pressure Medical Anthropology Quarterly, 14: 51-72
- Diener HC, Schorn CF, Bingel U, Dodick DW. (2008) The importance of placebo in headache research. Cephalalgia. 28:1003-11.{{PMID|18727647}}
- Archer TP, Leier CV. (1992) Placebo treatment in congestive heart failure. Cardiology.;81:125-33. {{PMID|1286471}}
- Marks R, Koutts J. (1975) Topical treatment of recurrent herpes simplex with cytosine arabinoside. Med J Aust. Apr 12;01(15):479-80.{{PMID|1097864}}>
- Asmar R, Safar M, Queneau P. (2001) Evaluation of the placebo effect and reproducibility of blood pressure measurement in hypertension. Am J Hypertens. 14:546-52. {{PMID|11411734}}
- Patel SM, Stason WB, Legedza A, Ock SM, Kaptchuk TJ, Conboy L, Canenguez K, Park JK, Kelly E, Jacobson E, Kerr CE, Lembo AJ. (2005) The placebo effect in irritable bowel syndrome trials: a meta-analysis. Neurogastroenterol Motil. 17:332-40. {{PMID|15916620}}
- Pitz M, Cheang M, Bernstein CN. (2005) Defining the predictors of the placebo response in irritable bowel syndrome. Clin Gastroenterol Hepatol. 3:237-47. {{PMID|15765443}}
- Macedo A, Baños JE, Farré M. (2008) Placebo response in the prophylaxis of migraine: a meta-analysis. Eur J Pain. 12:68-75. {{PMID|17451980}}
- La Mantia L, Eoli M, Salmaggi A, Milanese C. (1996) Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature. Ital J Neurol Sci. 17:135-9. {{PMID|8797067}}
- Wolf S. (1950) Effects of suggestion and conditioning on the action of chemical agents in human subjects; the pharmacology of placebos. J Clin Invest. 29:100-9. {{PMID|15399519}}
- Zhang Z, Wang Y, Wang Y, Xu F. (2008) Antiemetic placebo: reduce adverse drug interactions between chemotherapeutic agents and antiemetic drugs in cancer patients. Med Hypotheses.;70:551-5. {{PMID|17703892}}
- Shiao SY, Dune LS. (2006) Metaanalyses of acustimulations: effects on nausea and vomiting in postoperative adult patients. Explore (NY). 2:202-15. {{PMID|16781643}}
- Beecher HK, Keats AS, Mosteller F, Lasagna L. (1953) The effectiveness of oral analgesics (morphine, codeine, acetylsalicylic acid) and the problem of placebo "reactors" and "non-reactors". J Pharmacol Exp Ther. 109:393-400.{{PMID|13109703}}
- Baker B, Khaykin Y, Devins G, Dorian P, Shapiro C, Newman D. (2003) Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect. Can J Psychiatry. 48:381-7. {{PMID|12894612}}
- de la Fuente-Fernández R, Stoessl AJ. (2002) The placebo effect in Parkinson's disease. Trends Neurosci. 25:302-6. {{PMID|12086748}}
- Goetz CG, Wuu J, McDermott MP, Adler CH, Fahn S, Freed CR, Hauser RA, Olanow WC, Shoulson I, Tandon PK; Parkinson Study Group, Leurgans S. (2008) Placebo response in Parkinson's disease: comparisons among 11 trials covering medical and surgical interventions. Mov Disord. 23:690-9.{{PMID|18228568}}
- Black DW, Arndt S, Coryell WH, Argo T, Forbush KT, Shaw MC, Perry P, Allen J. (2007) Bupropion in the treatment of pathological gambling: a randomized, double-blind, placebo-controlled, flexible-dose study. J Clin Psychopharmacol. 27:143-50. {{PMID|17414236}}
- Eriksson E, Ekman A, Sinclair S, Sörvik K, Ysander C, Mattson UB, Nissbrandt H. (2008) Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder J Clin Psychopharmacol. 28:195-202. {{PMID|18344730}}
- Brockbank J, Gladman D. (2002) Diagnosis and management of psoriatic arthritis. Drugs. 62:2447-57. {{PMID|12421102}}
- Pace F, Maconi G, Molteni P, Minguzzi M, Bianchi Porro G. (1995) Meta-analysis of the effect of placebo on the outcome of medically treated reflux esophagitis. Scand J Gastroenterol. 30:101-5. {{PMID|7732329}}
- Fulda S, Wetter TC. (2008) Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain. 131:902-17. {{PMID|17932100}}
- Pollo A, Benedetti F. (2008) Placebo response: relevance to the rheumatic diseases. Rheum Dis Clin North Am. 34:331-49. {{PMID|18638680}}
- Bradford A, Meston C. (2007) Correlates of placebo response in the treatment of sexual dysfunction in women: a preliminary report. J Sex Med. 4:1345-51. {{PMID|17666035}}
- Oosterbaan DB, van Balkom AJ, Spinhoven P, van Dyck R. 2001 The placebo response in social phobia. J Psychopharmacol. 15:199-203. {{PMID|11565629}}
- Ilnyckyj A, Shanahan F, Anton PA, Cheang M, Bernstein CN. (1997) Quantification of the placebo response in ulcerative colitis.Gastroenterology. 112:1854-8. {{PMID|9178676}}
- Nyirjesy P, Sobel JD, Weitz MV, Leaman DJ, Small MJ, Gelone SP. (2001) Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study. Sex Transm Infect. 77:53-7.{{PMID|11158692}}
All Wikipedia content is licensed under the GNU Free Document License or is otherwise used here in compliance with the Copyright Act
|