Information AboutPlacebo |
|
Sometimes known as ''non-specific effects'' or Subject-expectancy Effect s, a so-called placebo effect occurs when a patient's symptoms are altered in some way (i.e., alleviated or exacerbated) by an otherwise inert treatment, due to the individual ''expecting'' or ''believing'' that it will work. Some people consider this to be a remarkable aspect of human physiology; others consider it to be an illusion arising from the way medical experiments are conducted. The placebo effect occurs when a patient takes an inert substance (“a sugar pill”) in conjunction with the suggestion from an authority figure that the pill will aid in healing and the patient’s condition improves. This effect has been known for years. The word "placebo" has been used in many somewhat varying meanings; see below. THE CONCEPT OF PLACEBO It has been observed often enough, yet still frequently overlooked, that the notion of placebo as it occurs in modern clinical discourse is not a rigorous concept, and despite many attempts, it has not been possible to provide a coherent definition. The most cited one is probably that of Arthur ShapiroThe Placebo Response; in Modern Perspectives in World Psychiatry. Howells, J (Ed), 1968; and several subsequent revisions, which together with others in the same vein, makes use of the idea of "non-specific" therapeutic effects, and thus merely shifts the explanatory burden to this equally undefined concept. In addition, as Moerman has pointed outMeaning, Medicine, and the "Placebo Effect"; Cambridge, 2002, such definitions assert at the same time that placebos are inert and that they produce the placebo effect, which is self-contradictory. In a detailed critique of Shapiro's approach, Grunbaum attempted to formulate a logically consistent definition,Explication and Implications of the Placebo Concept; in Placebo: Theory, Research and Mechanisms. White, Tursky, Schwartz (Eds), Guilford Press, 1985 but this in turn has been criticized on the grounds that it is uninformative in respect of the phenomenon itself – that is, the behaviour in a clinical setting of patients, bodies, physicians, and therapeutic maneuvers. In the view of Moerman and others, clinical science has burdened itself with a pseudo-concept, more confusing than useful, the correction of which will entail a revision of some foundational thinking in clinical medicine. Recent studies published in Proceedings of the National Academy of Sciences using advances in neuroscience (PET scans) have shown that placebos literally reduce pain in humans by changing their chemistry. Researchers at Columbia and Michigan University have shown that the brains of volunteers who believed that what they were taking was pain medication were shown to be spontaneously releasing opioids, or natural pain relief. (ABC News By SUSAN DONALDSON JAMES Aug. 1, 2007 http://abcnews.go.com/Health/Technology/story?id=3433101&page=1 ) According to that ABC report the Food and Drug Administration contends that as many as 75 percent of patients have had responses to sugar pills. It pointed out that all major clinical trials use placebo groups because the effect is significant and to be expected. This effect has been known for years. Generally, one third of a control group taking a placebo shows improvement and Harvard’s Herbert Benson says that the placebo effect yields beneficial clinical results in 60–90% of diseases, including angina pectoris, bronchial asthma, herpes simplex, and duodenal ulcers. (Harnessing the Power of the Placebo Effect and Renaming It "Remembered Wellness" Herbert Benson, M.D, Richard Friedman, Ph.D Annual Review of Medicine, February 1996, Vol. 47, Pages 193-199 (doi: 10.1146/annurev.med.47.1.193) The following are some of the issues pointing to a fundamental problem:
INERTNESS Although placebos are generally characterized as pharmacologically inert substances or formulations, sham treatments, or inactive procedures, they are only inert, sham, ineffective, or inactive in the particular sense that they have no known Cause And Effect relationship with any of the pre-designated, biochemical, physiological, behavioural, emotional and/or cognitive outcomes of the pharmacologically active and known-to-be- Efficacious Intervention that might have otherwise been applied (see Below ). Placebos are inactive or ineffective treatments or formulations; however a patient may experience either a positive or negative clinical effect while taking one. When a placebo is administered to mimic a previously administered drug, it may also incur the same side effects as the prior authentic drug. Most of these effects are thought to be psychological in nature or due to other unrelated factors. Not all placebos are equally effective. A placebo that involves ingestion, injection, or incision is often more powerful than a non-invasive technique. Placebos administered by authority figures such as general practitioners and other experts may also be more powerful than when this psychological authority effect is absent. They are, however, not inert, sham, or inactive in any other manner of speaking; and they may well, in and of themselves, generate considerable change within any given subject, at any given time, under any given circumstances. According to Shapiro: NOCEBO See Also: 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 will 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 her or his ability to get well, or even purely coincidental worsening of symptoms. ETYMOLOGY The word ''placebo'' is version), from where it became familiar to the public via the Office Of The Dead church service (see Placebo (at Funeral) for details). Whenever a placebo is requested in a medical prescription it may imply a statement by the Prescribing doctor that "This patient has come to me pleading for a treatment which does not exist or which I cannot or will not supply; I will please him by giving him something ineffectual and claiming that it is effectual." It could also indicate a belief that the effect was due to a subconscious desire of the patient to please the doctor. Since the ''placebo effect'' is in the ''patient'' not the doctor this may be more self-consistent. Early usage of the term does not indicate why it was chosen. Obecalp Sometimes a doctor who does this, says that the fake medicine is `Obecalp', which is "placebo" spelled backwards. [http://www.bookofjoe.com/2004/11/behindthemedspe_3.html (and many other links) EARLY USE OF PLACEBOS Originally, a placebo was a substance that a well-meaning doctor would give to a patient, telling him that it was a powerful drug (e.g., a Painkiller ), when in fact it was nothing more than a sugar pill. Thus, Hooper's medical dictionary of 1811 says placebo is "an epithet given to any medicine adapted more to please than benefit the patient." The subsequent reduction of the patient's symptoms was attributed to the patient's belief in the drug. (This category, particularly before the first Medicines Act was passed, may merge into Fake Medicine s.) MODERN CLINICAL APPLICATION Experimenters typically use placebos in the context of a Clinical Trial , in which a "test group" of patients receives the therapy being tested, and a " Control Group " receives the placebo. It can then be determined if results from the "test" group exceed those due to the placebo effect. If they do, the therapy or pill given to the "test group" is assumed to have had an effect. ORIGIN OF TERM "PLACEBO EFFECT" (1920) Perhaps Graves (1920) was the first to speak of the placebo effect, when he spoke of "''the placebo effects of drugs''" being manifested in those cases where "''a real psychotherapeutic effect appears to have been produced''".Graves (1920) p.1135. In 1933 (Evans and Hoyle) (using 90 subjects) and in 1937 (Gold, Kwit and Otto) (using 700 subjects) each published a study which compared the outcomes from the administration of an active drug and a dummy simulator (which both research groups called a placebo) in the same trial. Neither experiment displayed any significant difference between drug treatment and placebo treatment; leading the researchers to conclude that the drug exerted no specific effects in relation to the conditions being treated. In 1946, the Yale Biostatistician and Physiologist E. Morton Jellinek was the first to speak of either a "placebo reaction" or a "'''placebo response'''". He speaks of a "''response to '''placebo'''''" (p.88), those who "''responded to '''placebo'''''" (p.88), a "''reaction to '''placebo'''''" (p.89), and of "''reactors to '''placebo'''''" (p.90). From this, it is obvious that, to Jellinek, the terms "placebo response" and "placebo reaction" -- or the terms "placebo responder" and "placebo reactor" -- were identical and interchangeable. The general literature commonly misattributes the term "placebo effect" to Henry K. Beecher 's 1955 paper ''The Powerful Placebo'', where, however, he only speaks of placebo effects when he is contrasting them with '''drug effects'''; otherwise, he always speaks of "''placebo reactors''" and "''placebo non-reactors''". Beecher (1952), Beecher, Keats, Mosteller, and Lasagna (1953), Beecher (1959), consistently speak of "''placebo reactors''" and "''placebo non-reactors''"; they never speak of any "placebo effect". Beecher (1970) simply speaks of "''placebos''". ISOLATION OF CAUSATION According to Kleijnen and his colleagues,Kleijnen, et al., 1994, p.1347. healing is an interactive process between three influences:
::(Here, they are referring to an inherent self-healing force (such as that which naturally staunches a bleeding cut) similar to that of the élan Vital (“life force”) or the Vis Medicatrix Naturae (“healing power of nature”), per medium of which the patient recovers entirely without the physician’s intervention, rather than to some sort of active, intentional, purposeful arousal of a subject’s optimal Physiological , Psychosomatic and Somatopsychic healing resources by the therapist)
::(The term "non-specific effects" has many advantages; e.g., Psychopharmacological research that Hankoff (1999) conducted with colleagues in the 1950s, led them to conclude that “it is best to think of a range of nonspecific factors to account for the response to a medication (which can be both positive and negative), rather than speaking of a placebo reaction or a placebo reactor as an explanation” (p.199). Roberts, et al. (2001) describes these non-specific effects as “the nonpharmacologic benfits of the protocol involvement and of participants’ beliefs that they may be taking an active medication” (p.887))
These effects are not isolated mutually-exclusive effects and, rather than just adding, they may help or hinder each other to various degrees.Kleijnen, et al., 1994, p.1349. Also, Hyland (2003, p.348) notes that, in cases where “contextual factors contribute to a strong placebo response”, due to “the potentiating or adjunctive effect of the placebo response”, placebos can be used “potentiate the effect of an active treatment” that would have otherwise been far less efficacious. From this notion that a “drug” has a specific treatment effect (i.e., the effect for which it has been administered), Perlman (2001, p.283) draws attention to three other treatment effects: #non-specific effects: these are the side effects (“which are usually considered deleterious”); #unintended effects: these are the placebo effects (“which… are still considered to be for the most part uncontrolled and unscientific”); and #serendipitous effects: these are the “serendipitous effects of being in therapy, such as {Link without Title} organizing effects of the therapeutic structure, inadvertent role modelling, outside knowledge of the therapist, chance remarks or encounters, and the influence of auxiliary personnel”. In pursuit of establishing causation, the question “Who does what, with which, and to whom?” is central to task of identifying what are:
Gaddum (1954) also recognizes that "changes in the incidence or severity of diseases in a hospital may be due to changes in the diet or changes in the nurses, which happen to coincide with the introduction of a new treatment" (pp.195-196). In experiments with the Common Cold by Gold, Kwit & Otto (1937), in accounting for why those who received the placebo drug often experienced considerable benefit, Gold and his colleagues supposed that other, non-drug-related factors may have made a significant contribution to the apparent efficacy of the supposedly active drug, such as: #Spontaneous variations in the course of the pain''. #Change in the weather''. #Change of occupation or amount of work''. #Change of diet''. #Change in eating habits with increase in the amount of rest before and after meals''. #Condition of the bowels''. #Emotional stress''. #Change in domestic affairs''. #Confidence aroused in the treatment''. #Encouragement afforded by any new procedure''. #A change of the medical adviser''.Gold, Kwit & Otto (1937), p.2177. Also, due to the difficulty in ascribing causation, many phenomena overlap with, and are thus misattributed to, subjects' placebo responses (the phenomena are known as " Confounder s" or " Lurking Variable s", such as:
TECHNICAL CHALLENGES AND PITFALLS Preventing subjects recognizing placebo Appropriate use of a placebo in a Clinical Trial often requires or at least benefits from a Double-blind study design, which means that neither the experimenters nor the subjects know which subjects are in the "test group" and which are in the "control group". Placebo lacking active drug's early side-effects This sometimes causes difficulties, as a double-blind design cannot be easily applied to many treatments. For example, because some drugs have clear physiological impact, an inert pill (e.g., a sugar pill) would not be an effective placebo to test against any such drug. That is, an inert pill could not be used to demonstrate whether an active drug with noticeable physical Side Effects has more than a strong placebo effect. Most people can tell if they have ingested an active Antidepressant or anti-anxiety agent because of their Physiological effects, long before any Psychoactive response. The same is true of strong pain relievers. Adherence to placebo The Coronary Drug Project was intended to study the safety and effectiveness of safety of drugs for long-term treatment of coronary heart disease in men. Those in the placebo group who adhered to the placebo treatment (took the placebo regularly as instructed) showed nearly half the Mortality Rate as those who were not adherent.3 A similar study of women similarly found survival was nearly 2.5 times greater for those who adhered to their placebo.4 This apparent placebo effect may be caused by:
Need for psychoactive placebo Because a belief that one has received the active drug can produce a markedly heightened placebo effect, it is often necessary to use a psychoactive placebo in clinical trials; i.e., a drug that produces enough physical effects to encourage the belief in the control and experimental groups that they have received the active drug. A psychoactive placebo was used in the study, in which the experimental group received Psilocybin while the control group received a large dose of Niacin , a substance that produces noticeable physical effects. Walter Pahnke in 1962 described his ; Timothy Leary was the principal academic advisor for his dissertation. In it, Pahnke wrote of administering capsules that contained 30mg of Psilocybin extracted from Psychoactive mushrooms, and contrasting their effects with those of '''psychoactive placebos''', which contained the chemical Niacin in such a dosage that it produced very significant physiological responses. It was intended that these responses would lead the control subjects to believe they had received the '''psychoactive drug'''. The term "psychoactive placebo" is rare in the literature; but, when it is used, it always denotes a placebo of this type. For example, "''Neither the experienced investigator nor the naive {Link without Title} is easily fooled on the matter of whether he has received a Psychedelic substance or merely a Psychoactive placebo such as Amphetamine .''" (Harman, McKim, Mogar, Fadiman & Stolaroff, 1966, p.215) PLACEBOS IN CLINICAL TRIALS Placebo simulators are a standard Control component of most Clinical Trial s which attempt to make some sort of Quantitative assessment of the efficacy of new medicinal drugs; It is a view held by many "''that placebo-controlled studies often are designed in such a way that disadvantages the placebo condition''"(Herbert and Gaudino, 2005, pp.788-789). and, generally speaking, for a drug to be put on the market, it must be significantly more effective than its placebo counterpart. According to Yoshioka (1998), the first-ever randomized clinical trial was the trial conducted by the Medical Research Council (1948) into the efficacy of Streptomycin in the treatment of Pulmonary Tuberculosis .There were two test groups in this trial #those "''treated by streptomycin and bed-rest''", and #those "'' {Link without Title} by bed-rest alone''" (the control group). What made this trial exceptional was that the subjects were randomly allocated to their test groups. The up-to-that-time practice was to allocate subjects alternately to each group, based on the order in which they presented for treatment. This practice was considered to be extremely Biased , because those admitting each patient knew to which group that patient would be allocated (and it was considered that the decision to admit or not admit a specific patient might be influenced by the experimenter's knowledge of the nature of their illness, and their knowledge of the group to which the alternate allocation demanded they would occupy). In recent times, the practice of using an additional Natural History Group as the trial's so-called "''third arm''" has emerged; and trials are conducted using three Randomly-selected equally-matched trial groups, David (1949, p.28) wrote: "''... it is necessary to remember the adjective ‘random’ the term ‘random sample’ should apply to the method of drawing the sample and not to the sample itself.''". #The Active drug group ('''A'''): who receive the active test drug. #The Placebo drug group ('''P'''): who receive a placebo drug that simulates the active drug. #The Natural history group ('''NH'''): who receive no treatment of any kind (and whose condition, therefore, is allowed to run its ''natural'' course). The outcomes within each group are observed, and compared with each other, allowing us to measure: #The efficacy of the active drug's treatment: the difference between '''A''' and '''NH''' (i.e., '''A-NH'''). #The efficacy of the entire treatment process alone: the difference between '''P''' and '''NH''' (i.e., '''P-NH'''). #The efficacy of the active drug's active ingredient: the difference between '''A''' and '''P''' (i.e., '''A-P'''). #The magnitude of the placebo response: the difference between '''P''' and '''NH''' (i.e., '''P-NH'''). Note that, depending upon the focus of your interest, the value of P-NH can either indicate the ''efficacy of the entire treatment process'' or the ''magnitude of the "placebo response"''. The results of these comparisons then determine whether or not a particular drug is considered efficacious. In recent times, as the demands for the scientific Validation of the various claims that are made for the efficacy of various so-called "talking therapies" (such as Hypnotherapy , Psychotherapy , counselling, and non-drug Psychiatry ) has significantly increased, there is continuing controversy over what might or might not be an appropriate placebo for such therapeutic treatments. In 2005, the ''Journal of Clinical Psychology'', an eminent peer-reviewed journal (founded in 1945), devoted an entire issue to the question of "''The Placebo Concept in Psychotherapy''", and contained a wide range of articles that made many valuable contributions to this overall discussion. THE PLACEBO RESPONSE AS AN INDEX In certain clinical trials of particular drugs, it may happen that the level of the "placebo responses" manifested by the trial's subjects are either considerably higher or lower (in relation to the "active" drug's effects) than one would expect from other trials of similar drugs. In these cases, With All Other Things Being Equal , it is entirely reasonable to conclude that:
However, in particular cases such as the use of Cimetidine to treat ulcers ( See Below ), a significant level of placebo response can also prove to be an index of how much the treatment has been directed at a wrong target. TRIALS "s of modern, scientific, conventional medicine began to emerge, medical scholars began to routinely question:
In many cases, active agents were identified in supposedly efficacious treatments; but it was found that some treatments had no efficacy whatsoever; and, regardless of how much they were accepted in the medical profession, or what they were supposed to do, they were medically useless. Many, such as Pepper (1945, p.410) would strongly argue that, before the Countess Of Chinchón Learned Of The Medicinal Properties of Cinchona bark (perhaps the first time a real active ingredient had been isolated and identified), "there was {Link without Title} basis for terming anything a placebo". The aim of a Clinical Trial is to determine what treatments, delivered in what circumstances, to which patients, in what conditions, are the most efficacious; as well to obtain objective evidence of what treatments are efficacious and also specific,Chambless & Hollon (1998) or are intentionally efficacious and also specific.Lohr, Olatunji, Parker & DeMaio (2005). Gaddum (1953, p.195) wrote: "''The first object of a therapeutic trial is to discover whether the patients who receive the treatment under investigation are cured more rapidly, more completely or more frequently, than they would have been without it.''" SIGNIFICANT TRIALS Citrus fruit and scurvy (1747) In 1747, James Lind (1716-1794), the Naval Surgeon on HMAS Salisbury , conducted what was most likely the first-ever Clinical Trial when he investigated the efficacy of Citrus Fruit in cases of Scurvy . He randomly divided twelve scurvy patients, whose "''cases were as similar as I could have them''", into six pairs. Each pair was given a different remedy. Lind’s approach can still be seen in the way that the comparative efficacy of various treatments for particular sorts of Cancer are determined, by examining and comparing the Five Year Survival Rate s of those who have been treated with each of the different interventions. He noted that the pair who had been given the Citrus were so restored to health within six days of treatment that one of them returned to duty, and the other was well enough to attend the rest of the sick.Dunn (1997), p.F65. According to Lind’s 1753 ''Treatise on the Scurvy in Three Parts Containing an Inquiry into the Nature, Causes, and Cure of the Disease, Together with a Critical and Chronological View of what has been Published of the Subject'', the remedies were: #one quart of Cider per day, #twenty-five drops of elixir Vitriol (aromatic Sulphuric Acid ) three times a day, #two spoonfuls of Vinegar three times a day, #a course of sea-water (half a Pint every day), #two Orange s and one Lemon each day, #an Electuary (Dunn, 1997, p.F65). Gaddum (1954, p.196) wrote that the Electuary had been recommended to Lind by a hospital surgeon, and that it contained Garlic , Mustard , Balsam Of Peru , and Myrrh . Animal magnetism (1784) In 1784, the French Royal Commission into the existence of Animal Magnetism investigated the practices of Charles D’Eslon (1739-1786) and compared the effects of his allegedly "magnetized" water with that of plain water.Gauld (1992), p.28. It did not examine the practices of Franz Mesmer , but examined the significantly different practices of his associate Charles d’Eslon. See Animal Magnetism for more information. Perkins tractors (1799) In 1799, John Haygarth investigated the efficacy of medical instruments called " Perkins Tractors ", by comparing the results from ''dummy'' wooden tractors with a set of allegedly "active" metal tractors.Green, (2002); Haygarth (1801). Diluted quassia as placebo (1863) In 1863 Austin Flint (1812–1886) conducted the first-ever trial that directly compared the efficacy of a dummy simulator with that of an active treatment; although Flint's examination did not compare the two against each other in the same trial. Even so, this was a significant departure from the (then) customary practice of contrasting the consequences of an active treatment with what Flint described as "''the natural history of untreated disease''".Flint (1863), p.18. Flint’s paper is the first time that either of the terms "placebo" or "'''placeboic remedy'''" were ever used to refer to a dummy simulator in a clinical trial. Flint (1863, p.21) treated 13 hospital inmates who had Rheumatic Fever ; 11 were " Acute ", and 2 were "sub-acute". He then compared the results of his dummy "placeboic remedy" with that of the active treatment’s already well-understood results. (Flint had previously tested, and reported on, the active treatment’s efficacy.) There was no significant difference between the results of the active treatment and his "placeboic remedy" in 12 of the cases in terms of disease duration, duration of convalescence, number of joints affected, and emergence of Complication s (pp.32-34). In the thirteenth case, Flint expressed some doubt as to whether the particular complications that had emerged (namely, Pericarditis , Endocarditis , and Pneumonia ) would have been prevented if that subject had been immediately given the "active treatment" (p.36). Willow bark , which eventually led to the drug Aspirin . Mercury for syphilis Treatment of Syphilis with Salve s made From Mercury , proved to have no medical effect. A headache remedy (1946) In post- World War II 1946 , pharmaceutical chemicals were in short supply. One U.S. headache remedy manufacturer sold a drug that was comprised of three ingredients: a, '''b''', and '''c'''. Chemical '''b''' was in short supply. Jellinek was asked to test whether or not the headache drug's overall efficacy would be reduced if ingredient b was missing. Jellinek set up a complex trial involving 199 subjects, all of whom suffered from "''frequent headaches''". (Originally there were 200 subjects, but one did not complete the trial.) The subjects were randomly divided into four test groups. He prepared four test drugs, involving various Permutation s of the three drug constituents, with a placebo as a Scientific Control . The structure of this trial is significant because, in those days, the only time placebos were ever used "''was to express the efficacy or non-efficacy of a drug in terms of "how much better" the drug was than the "placebo''". (Jellinek (1946), p.88. Note that the trial conducted by Austin Flint is an example of such a drug efficacy vs. placebo efficacy trial.) The four test drugs were identical in shape, size, colour and taste:
Each time a subject had a headache, they took their group’s designated test drug, and recorded whether their headache had been relieved (or not). Although "some subjects had only three headaches in the course of a two-week period while others had up to ten attacks in the same period", the data showed a "great consistency" across all subjects (Jellinek, 1946, p.88). Every two weeks the groups’ drugs were changed; so that by the end of eight weeks, all groups had tested all the drugs. The stipulated drug (i.e., A, '''B''', '''C''', or '''D''') was taken as often as necessary over each two-week period, and the two week sequences were: #A, '''B''', '''C''', '''D''' #B, '''A''', '''D''', '''C''' #C, '''D''', '''A''', '''B''' #D, '''C''', '''B''', '''A'''. Each group took a test remedy for two weeks. The trial lasted eight weeks, and by the end of the trial all groups had taken each test drug for two weeks (although each group had taken them in a different sequence). Over the entire population of 199 subjects, 120 of the subjects responded to the placebo, and 79 did not; i.e., there were 120 "''subjects reacting to placebo''" and 79 "''subjects not reacting to placebo''".Jellinek (1946), p.89. At first glance there was no difference between the self-reported "success rates" of Drugs A, '''B''', and '''C''' (84%, 80%, and 80% respectively) (the "success rate" of the simulating placebo Drug '''D''' was 52%); and, from this, it appeared that ingredient '''b''' was completely unnecessary. However, in quite a remarkable way, the trial eventually did demonstrate that ingredient b '''''did''''' make a significant contribution to the remedy’s efficacy. Examining his data more closely, Jellinek discovered that there was a very significant difference in responses between the 120 placebo-responders and the 79 non-responders. The 79 non-responders' reports showed that if they were considered as an entirely separate group, there was a significant difference the "success rates" of Drugs '''A''', '''B''', and '''C''': viz., 88%, 67%, and 77%, respectively. And because this significant difference in relief from the test drugs could only be attributed to the presence or absence of ingredient b, he concluded that ingredient b was essential (thus contradicting his initial conclusion, derived from the comparison between the "success rates" for all test subjects, that Drugs '''A''', '''B''', and '''C''' were equally efficacious). There were two further repercussions from this trial:
Cimetidine and stomach ulcers (1983) This test wrongly seemed to show that Cimetidine was a placebo, because they did not know that the bacterium '' Helicobacter Pylori '' was sometimes present and interfering with results. In 1983 of the treated area. He 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). Further examination revealed that many of these trials had been conducted in such a way that the gap between the active drugs and the placebo controls was "not because 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. Moerman argues that "what is demonstrated in {Link without Title} studies is not enhanced healing in drug groups, but reduced healing in placebo groups" (p.14). Moerman also noted the results of two studies (one conducted in Germany, the other in Denmark), which examined "ulcer Relapse in healed patients". Each study 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). This led Moerman to remark: “we may be able to go so far as to say that while active drug “heals” ulcers, placebo treatment can “cure” ulcer disease” (p.14). These results of a 90% placebo response rate, and a placebo-healed relapse rate 20% that of the active drug seems to indicate that the drug ''Cimetidine'' was not effective in inhibiting gastric acid secretion. However, as we now know, the majority of gastric or duodenal ulcers are not due to excessive gastric acid secretion caused by Stress or Spicy Food , but are due to the Bacterium '' Helicobacter Pylori '', it is highly significant that this high response rate and low relapse rate can now be interpreted otherwise: it was indicating that the drug's prescribers had chosen the wrong target for their therapeutic intervention (and, as a consequence, we now know that they had chosen what might be termed an "inappropriate target but correct drug", rather than a "correct target but inappropriate drug" as was first supposed). Placebo-controlled studies Beecher (1955) reported that about a quarter of patients who were administered a placebo, for example against back pain, reported a relief or diminution of pain. Remarkably, not only did the patients ''report'' improvement, but the improvements themselves were often objectively measurable, and the same improvements were typically not observed in patients who did not receive the placebo. Because of this effect, government regulatory agencies approve new drugs only after tests establish not only that patients respond to them, but also that their effect is greater than that of a placebo (by way of affecting more patients, by affecting responders more strongly or both). Such a test or Clinical Trial is called a ''placebo-controlled'' study. Because a doctor's belief in the value of a treatment can affect his or her behaviour, and thus what his or her patient believes, such trials are usually conducted in " Double-blind " fashion: that is, not only are the patients made unaware when they are receiving a placebo, the doctors are made unaware too. Recently, it has even been shown that "mock" surgery can have similar effects, and so some surgical techniques must be studied with placebo controls (rarely double blind, due to the difficulty involved). To merit approval, the group receiving the experimental treatment must experience a greater benefit than the placebo group. Nearly all studies conducted this way show some benefit in the placebo group. For example, Khan published a Meta-analysis of studies of investigational Antidepressant s and found a 30% reduction in suicide and attempted suicide in the placebo groups and a 40% reduction in the treated groups. (Khan 2000) However, studies generally do not include an untreated group, so determining the actual size of the placebo effect, compared to totally untreated patients, is difficult. PLACEBO EFFECT ON VARIOUS SYMPTOMS Placebo and pain Careful studies have shown that the placebo effect can alleviate pain, although the effect is more pronounced with pre-existing pain than with experimentally induced pain. People can be Conditioned to expect Analgesia in certain situations. When those conditions are provided to the patient, the brain responds by generating a pattern of neural activity that produces objectively quantifiable analgesia. (Benedetti 2003, Wager 2004) Evans argued that the placebo effect works through a suppression of the Acute Phase Response , and as a result does not work in medical conditions that do not feature this. (Evans 2005) The acute phase response consists of inflammation and sickness behaviour:
Placebo and depression A brain-imaging study found that depressed patients who responded to the placebo effect showed changes in cerebral blood flow, which were similar to the changes in brain function seen in patients who responded to anti-depressant medication. (Leuchter 2002) Other studies argue that up to 75% of the effectiveness of anti-depressant medication is due to the placebo-effect rather than the treatment itself. (Khan 2000) Withdrawal symptoms on discontinuance of placebo The Women's Health Initiative study of Hormone Replacement Therapy for Menopause was discontinued after participants still in the program had been taking either Hormone s or 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. Pain and stiffness ( Musculoskeletal symptoms) were the most frequently reported symptoms in both the placebo group (22.2%) and the hormone group (36.8%), exceeding other symptoms by more than 10%. Of those reporting pain and stiffness, 54.7% in the hormone group and 38.3% in the placebo group had these symptoms at the onset of therapy. Tiredness | |||
|
|||
|
|