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"The physician's belief in the treatment and the patient's faith in the physician exert a mutually reinforcing effect; the result is a powerful remedy that is almost guaranteed to produce an improvement and sometimes a cure." -- Petr Skrabanek and James McCormick, Follies and Fallacies in Medicine, p. 13.
The placebo effect is the measurable, observable, or felt improvement in health or behavior not attributable to a medication or invasive treatment that has been administered. The placebo effect is not mind over matter; it is not mind-body medicine. 'The placebo effect' has become a catchall term for a positive change in health not attributable to medication or treatment. As is explained below, the change can be due to many things, such as regression to the mean, spontaneous improvement, reduction of stress, misdiagnosis in the first place, subject expectancy, classical conditioning, etc.
A placebo (Latin for "I shall please") is a pharmacologically inert substance (such as saline solution or a starch tablet) that seems to produce an effect similar to what would be expected of a pharmacologically active substance (such as an antibiotic).
By extension, "fake" surgery and "fake" therapies are considered placebos.
The idea of the placebo in modern times originated with H. K. Beecher. He evaluated 15 clinical trials concerned with different diseases and found that 35% of 1,082 patients were satisfactorily relieved by a placebo alone ("The Powerful Placebo," 1955). Other studies have since calculated the placebo effect as being even greater than Beecher claimed. For example, studies have shown that placebos are effective in 50 or 60 percent of subjects with certain conditions, e.g., "pain, depression, some heart ailments, gastric ulcers and other stomach complaints."* And, as effective as the new psychotropic drugs seem to be in the treatment of various brain disorders, some researchers maintain that there is not adequate evidence from studies to prove that the new drugs are more effective than placebos.
Beecher started a wave of studies aimed at understanding how something (improvement in health) could be produced by nothing (the inactive placebo). Unfortunately, many of the studies have not been of particularly high quality and have assumed that any measured improvement was caused by the placebo. In fact, it has been argued by Kienle and Kiene (1997) that, contrary to what Beecher claimed, a reanalysis of his data found "no evidence of any placebo effect in any of the studies cited by him." The reported improvements in heath were real but were due to other things that produced "false impressions of placebo effects." The reanalysis of Beecher's data claims that the improvements were due to:
Spontaneous improvement, fluctuation of symptoms, regression to the mean, additional treatment, conditional switching of placebo treatment, scaling bias, irrelevant response variables, answers of politeness, experimental subordination, conditioned answers, neurotic or psychotic misjudgment, psychosomatic phenomena, misquotation, etc.
What the reanalysis shows is that there are a number of factors that can affect many treatments and the evaluation of those treatments, making it very difficult to be sure just what it is about an intervention that produces improvement or perceived improvement. We must also consider "artifacts such as the natural history of a disease (that is, the tendency for people to get better or worse during the course of an illness irrespective of any treatment at all), the fact that people behave differently when they are participating in an experiment than when they are not, a desire to please the experimental staff by providing socially desirable answers..." (Bausell 2007: 27), and a host of other factors unrelated to the pill we are administering and independently of any mechanism that we believe is producing any observed effects.
In May 2001, The New England Journal of Medicine published an article that called into question the validity of the placebo effect. "Is the Placebo Powerless? An Analysis of Clinical Trials Comparing Placebo with No Treatment" by Danish researchers Asbjørn Hróbjartsson and Peter C. Götzsche "found little evidence in general that placebos had powerful clinical effects." Their meta-analysis of 114 studies found that "compared with no treatment, placebo had no significant effect on binary outcomes, regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect, but the effect decreased with increasing sample size, indicating a possible bias related to the effects of small trials." (Most of the studies evaluated by Hróbjartsson and Götzsche were small: for 82 of the studies the median size was 27 and for the other 32 studies the median was 51.)
"The high levels of placebo effect which have been repeatedly reported in many articles, in our mind are the result of flawed research methodology," said Dr. Hróbjartsson, professor of medical philosophy and research methodology at the University of Copenhagen.*
Typical of the kind of flawed research methodology Hróbjartsson is referring to would be that of surgeon J. Bruce Moseley who performed fake knee surgery on eight of ten patients. (Fake surgery involves making an incision on the knee and stitching it up.) Six months after the surgery all the patients were satisfied customers. Rather than conclude that the patients didn't need surgery or that the surgery was useless because in time the patients would have healed on their own, he and others concluded that the healing of the eight who did not have surgery was due to the placebo effect, while the two who had real surgery were better because of having had the operation. Irving Kirsch and Guy Sapirstein have been accused of making the same kind of methodological error in their controversial meta-analysis that found that anti-depressants work by the placebo effect, rather than that anti-depressants are unnecessary and useless.
One more example should suffice to make the point that better designs of placebo studies are needed.
Forty years ago, a young Seattle cardiologist named Leonard Cobb conducted a unique trial of a procedure then commonly used for angina, in which doctors made small incisions in the chest and tied knots in two arteries to try to increase blood flow to the heart. It was a popular technique—90 percent of patients reported that it helped—but when Cobb compared it with placebo surgery in which he made incisions but did not tie off the arteries, the sham operations proved just as successful. The procedure, known as internal mammary ligation, was soon abandoned ("The Placebo Prescription" by Margaret Talbot, New York Times Magazine, January 9, 2000).*
Did Cobb show that this kind of surgery works by the placebo effect? Or did he show that the surgery was unnecessary because most of the patients would have healed on their own if nothing had been done?
To rule out the natural history of a disease or regression to the mean, many researchers have used a third control group—those who receive no treatment at all. If the placebo group shows better results than the group getting nothing, then surely the placebo is effective. Hróbjartsson and Götzsche think most of these studies, too, are flawed, mainly due to having samples that are too small or due to patients who make reports aimed at pleasing the researcher.
After the publication of the Hróbjartsson and Götzsche study, Dr. John C. Bailar III said in an editorial that accompanied the study: "The shoe is on the other foot now. The people who claim there are placebo effects are going to have to show it." The need, he said, is for large, rigorously designed studies that clearly define and measure effects of drugs and therapies versus placebos versus no intervention at all. These studies will have to clearly distinguish objective measurements (such as blood pressure, cholesterol levels, etc.) and subjective measurements (such as reports of pain or evaluative sensory observations by researchers, e.g., "I can see your tumor is smaller" or "I can see you are not as depressed as before").
The kind of study called for by Dr. Bailar has been done and several such studies are reviewed in chapter nine of R. Barker Bausell's Snake Oil Science (2007): "How We Know That the Placebo Effect Exists." One in particular is worth reviewing here. It was published in the Journal Pain two months after the Hróbjartsson and Götzsche article. "Response expectancies in placebo analgesia and their clinical relevance" was the work of Antonella Pollo et al. and demonstrated that placebos can help people with serious pain. The following is from their abstract:
Thoracotomized patients were treated with buprenorphine [a powerful pain reliever] on request for 3 consecutive days, together with a basal intravenous infusion of saline solution. However, the symbolic meaning of this basal infusion was changed in three different groups of patients. The first group was told nothing about any analgesic effect (natural history). The second group was told that the basal infusion was either a powerful painkiller or a placebo (classic double-blind administration). The third group was told that the basal infusion was a potent painkiller (deceptive administration). Therefore, whereas the analgesic treatment was exactly the same in the three groups, the verbal instructions about the basal infusion differed. The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three-days treatment. We found that the double-blind group showed a reduction of buprenorphine requests compared to the natural history group. However, this reduction was even larger in the deceptive administration group. Overall, after 3 days of placebo infusion, the first group received 11.55 mg of buprenorphine, the second group 9.15 mg, and the third group 7.65 mg. Despite these dose differences, analgesia was the same in the three groups. These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects, which in turn trigger a dramatic change of behaviour leading to a significant reduction of opioid intake.
The patients who thought their IV contained a powerful pain reliever required 34% less of the analgesic than the patients who weren't told anything about their IV and 16% less than the patients who were told the IV could be either a powerful pain killer or a placebo. Each group got exactly the same amount of pain killer but their requests for the analgesic differed dramatically. The only significant difference among the three groups was the set of verbal instructions about the basal infusion. The study was too short for the differences to be explained by the natural history of recovery, regression, or any of the other alternatives found by Hróbjartsson and Götzsche.
Several things are worth noting about
this experiment. The setting involves treatment being provided by medical
personnel in a medical facility. This kind of setting usually involves a
strong desire for recovery or relief on the part of the patient, as well
as a belief that the treatment will be effective. The different verbal
instructions about the basal IV would lead to different expectations.
Belief, motivation, and expectation are essential to some forms of the placebo effect.
Together, they are referred to as the
Classical conditioning and
suggestion by an authoritative healer seem to be triggering mechanisms for
the this form of placebo effect (Bausell 2007: 131).
the psychological hypothesis: it's all in your mind
Some believe the placebo effect is purely psychological. Irving Kirsch, a psychologist at the University of Connecticut, believes that the effectiveness of Prozac and similar drugs may be attributed almost entirely to the placebo effect. He and Guy Sapirstein analyzed 19 clinical trials of antidepressants and concluded that the expectation of improvement, not adjustments in brain chemistry, accounted for 75 percent of the drugs' effectiveness (Kirsch 1998). "The critical factor," says Kirsch, "is our beliefs about what's going to happen to us. You don't have to rely on drugs to see profound transformation." In an earlier study, Sapirstein analyzed 39 studies, done between 1974 and 1995, of depressed patients treated with drugs, psychotherapy, or a combination of both. He found that 50 percent of the drug effect is due to the placebo response.
A person's beliefs and hopes about a treatment, combined with their suggestibility, may have a significant biochemical effect, however. Sensory experience and thoughts can affect neurochemistry. The body's neurochemical system affects and is affected by other biochemical systems, including the hormonal and immune systems. Thus, it is consistent with current knowledge that a person's hopeful attitude and beliefs may be very important to their physical well-being and recovery from injury or illness. But it does not follow from this fact that if the patient has hope will she recover. Nor does it follow from this fact that if a person is not hopeful she will not recover.
The psychological explanation seems to be the one most commonly believed. Perhaps this is why many people are dismayed when they are told that the effective drug they are taking is a placebo. This makes them think that their problem is "all in their mind" and that there is really nothing wrong with them. Yet, there are too many studies that have found objective improvements in health after being given placebos to support the notion that the placebo effect is entirely psychological.
Doctors in one study successfully eliminated warts by painting them with a brightly colored, inert dye and promising patients the warts would be gone when the color wore off. In a study of asthmatics, researchers found that they could produce dilation of the airways by simply telling people they were inhaling a bronchodilator, even when they weren't. Patients suffering pain after wisdom-tooth extraction got just as much relief from a fake application of ultrasound as from a real one, so long as both patient and therapist thought the machine was on. Fifty-two percent of the colitis patients treated with placebo in 11 different trials reported feeling better -- and 50 percent of the inflamed intestines actually looked better when assessed with a sigmoidoscope ("The Placebo Prescription" by Margaret Talbot, New York Times Magazine, January 9, 2000).*
It is unlikely that such effects are purely psychological, though I must admit that I don't find the expression 'purely psychological' very precise or clear.
In fact, Martina Amanzio et al.
(2001) demonstrated that "at least part of the physiological basis for the
placebo effect is opioid in nature" (Bausell 2007: 160). We can
be conditioned to release such chemical
substances as endorphins, catecholamines, cortisol, and adrenaline. One
reason, therefore, that people report pain relief from both acupuncture
and sham acupuncture
is may be that both are placebos that stimulate the opioid
Another popular belief is that a process of treatment that involves showing attention, care, affection, etc., to the patient/subject, a process that is encouraging and hopeful, may itself trigger physical reactions in the body which promote healing. According to Dr. Walter A. Brown, a psychiatrist at Brown University:
...there is certainly data that suggest that just being in the healing situation accomplishes something. Depressed patients who are merely put on a waiting list for treatment do not do as well as those given placebos. And—this is very telling, I think—when placebos are given for pain management, the course of pain relief follows what you would get with an active drug. The peak relief comes about an hour after it's administered, as it does with the real drug, and so on. If placebo analgesia was the equivalent of giving nothing, you'd expect a more random pattern ("The Placebo Prescription" by Margaret Talbot, New York Times Magazine, January 9, 2000).*
Dr. Brown and others believe that the placebo effect is mainly or purely physical and due to physical changes that promote healing or feeling better.
So, what is the explanatory mechanism for the placebo effect? Some think it is the process of administering it. It is thought that the touching, the caring, the attention, and other interpersonal communication that is part of the controlled study process (or the therapeutic setting), along with the hopefulness and encouragement provided by the experimenter/healer, affect the mood, expectations, and beliefs of the subject, which in turn triggers physical changes such as release of endorphins, catecholamines, cortisol, or adrenaline. The process reduces stress by providing hope or reducing uncertainty about what treatment to take or what the outcome will be. The reduction in stress prevents or slows down further harmful physical changes from occurring. The healing situation provokes a conditioned response. The patient's been healed before by the doctor (or thinks she's been healed before by the doctor) and expects to be healed again.
the genetic connection
Because the placebo effect shows profound variability among individuals, some researchers have looked for evidence of a genetic predisposition to susceptibility to placebo effects. Andrew Leuchter et al. postulated that placebos act through central reward pathways modulated by monoamines, which are under strong genetic control. Their findings "support the hypothesis that genetic polymorphisms modulating monoaminergic tone are related to degree of placebo responsiveness in major depressive disorder."* The researchers stressed that genetics is not the sole explanation for a placebo response, which is likely to be influenced by several biological and psychosocial factors.*
The power of the placebo effect has led to an ethical dilemma. One should not deceive other people, but one should relieve the pain and suffering of one's patients. Should one use deception to benefit one's patients? Is it unethical for a doctor to knowingly prescribe a placebo without informing the patient? If informing the patient reduces the effectiveness of the placebo, is some sort of deception warranted in order to benefit the patient? Some doctors think it is justified to use a placebo in those types of cases where a strong placebo effect has been shown and where distress is an aggravating factor.* Others think it is always wrong to deceive the patient and that informed consent requires that the patient be told that a treatment is a placebo treatment. Others, especially complementary and alternative medicine (CAM) practitioners, don't even want to know whether a treatment is a placebo or not. Their attitude is that as long as the treatment is effective, who cares if it a placebo? This attitude is changing, however, and it is now common to find defenders of CAM admit that CAM is placebo medicine and go on to claim that that's why CAM is good medicine!
While it may be unethical to knowingly package, prescribe, or sell placebos as magical cures, the CAM folks seem to think they are ethical because they really believe in their chi, meridians, yin, yang, prana, vata, pitta, kapha, auras, chakras, energies, spirits, succussion, natural herbs, water with precise and selective memory, subluxations, cranial and vertebral manipulations, douches and irrigations, body maps, divinities, and various unobservable processes that allegedly carry out all sorts of magical analgesic and curative functions.
While skeptics may reject faith, prayer and "alternative" medical practices such as bioharmonics, chiropractic, and homeopathy, such practices may not be without their salutary effects. Clearly, they can't cure cancer or repair a punctured lung, and they might not even prolong life by giving hope and relieving distress as is sometimes thought. But administering placebo therapies does involve interacting with the patient in a caring, attentive way, and this can provide some measure of comfort. However, to those who say "what difference does it make why something works, as long as it seems to work" I reply that it is likely that there is something that works even better and might even be cheaper. Worse, some people might seek out an alternative healer for a serious disorder that isn't affected by the CAM treatment but could be relieved or cured by scientific medicine. Furthermore, placebos may not always be beneficial or harmless. John Dodes notes:
Patients can become dependent on nonscientific practitioners who employ placebo therapies. Such patients may be led to believe they're suffering from imagined "reactive" hypoglycemia, nonexistent allergies and yeast infections, dental filling amalgam "toxicity," or that they're under the power of qi or extraterrestrials. And patients can be led to believe that diseases are only amenable to a specific type of treatment from a specific practitioner (The Mysterious Placebo by John E. Dodes, Skeptical Inquirer, Jan/Feb 1997).
In other words, the placebo can be an open door to malfeasance. R. Barker Bausell speculates that since complementary and alternative medicine (CAM) practitioners' greatest asset is their nourishment of hope (2007: 294), "such therapies may be engendering nothing more than the expectation that they will reduce pain by elaborate explanations, promises, and ceremonies" (p. 149). Packaging placebos is big business and is likely to get even bigger. The only thing that could slow down CAM atavism would be the sudden appearance of horrible side effects issuing from treatments like aura cleansings or homeopathic douches.
I'd say that there's about as much chance of that happening as there is of John Edward or James Van Praagh announcing to an audience that a spirit is telling him that one of the paying customers is an axe murderer.
See also conditioning, confirmation bias, control study, communal reinforcement, magical thinking, nocebo, Occam's razor, post hoc fallacy, regressive fallacy, selective thinking, self-deception, subjective validation, testimonials, and wishful thinking.
For examples of beliefs deeply affected by the placebo effect see the following entries in The Skeptic's Dictionary:
- angel therapy
- animal quacker
- anthroposophic medicine
- applied kinesiology
- aura therapy
- Ayurvedic medicine
- Bach's flower therapy
- chelation therapy
- complex homeopathy
- coning (ear candling)
- craniosacral therapy
- dolphin-assisted therapy
- Dr. Fritz - "energy healing"
- Eye Movement Desensitization Reprocessing (EMDR)
- facilitated communication
- faith healing
- healing touch
- joy touch
- magnet therapy
- psychic surgery
- therapeutic touch
- urine therapy
response to Mark Crislip's claim that there is no placebo effect
(from the SD Newsletter July 7, 2008)
Mark Crislip, M.D., in a recent guest column on Science-based Medicine, writes:
I do not think there is a placebo effect. Period. None. Zip. Zero. Nada. Zilch.
Crislip doesn't beat around the bush. Fair enough. Since I've been maintaining that hypnotherapy is indistinguishable from a placebo and that the many satisfied customers of things like acupuncture and homeopathy can be explained by the placebo effect, I think I ought to respond.
Crislip is a practicing infectious disease doctor in Portland, Oregon. He is author of the Quackcast podcast (a review of supplements, complementary and so-called alternative medicine), a blog, and a couple of other podcasts on medical issues.
He begins his argument by dividing outcomes that don't occur into two types: objective and subjective. He explains this division by reference to the 2001 article by Asbjorn Hrobjartsson, M.D., and Peter C. Götzsche, M.D.: "Is the Placebo Powerless - An Analysis of Clinical Trials Comparing Placebo with No Treatment," which appeared in the New England Journal of Medicine. That study found no significant difference between placebo and no treatment groups, but it did find "possible small benefits in studies with continuous subjective outcomes and for the treatment of pain." The objective part of pain has to do with trauma to nerves and signals to the brain. The subjective part has to do with the feeling and appreciation of pain. In short, there is the bodily trauma and there is your feeling and perception of the trauma to your body. They are, obviously, quite distinct.
Crislip's view is that "the placebo effect with pain is a mild example of cognitive behavioral therapy (CBT); the pain stays the same, it is the emotional response that is altered." He doesn't fill in the argument here, but he seems to be implying that since we do not consider CBT a placebo and CBT works by altering emotional responses, other treatments that work by altering emotional responses are not placebos, either.
Crislip then analyzes a 2006 BMJ article: "Sham device v inert pill: randomised controlled trial of two placebo treatments. The objective of the study was to determine whether sham acupuncture has a greater placebo effect than an inert pill in patients with persistent arm pain. The researchers found no difference in objective results but the sham acupuncture had greater subjective effects than the placebo pill. The researchers concluded: "Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals." Crislip concludes: "Ain't no such thing as a placebo effect, only a change in perception." However, in presenting his defense, Crislip provides evidence for an important element of placebo and nocebo effects: suggestion. He writes:
Two different placebos decreased pain, one placebo was better than the other. Why?
The answer may be in another interesting result of the study: side effects. Patients were told in the informed consent what the side effects of the active therapies were, even though initially they all were getting placebo. And the informed consent worked to ‘cause’ side effects: three of the placebo subjects dropped out from dry mouth and fatigue and 10% of the sham had increased pain after the needle was ‘removed’.
Crislip then goes on to unintentionally add support for another important element of placebo effects: expectation. There is good evidence, he notes, that expectation significantly affects how things taste to us. "People have the result they expect to have and the side effects they are told they will have." If I understand him, he seems to be saying that if there is only a subjective effect to a treatment, then there is no placebo effect. If this is so, then his argument is a one of semantics. So, when he writes "In humans there is no ‘real’ effect from placebo," he means there is no objective effect, only a subjective effect.
He concludes his argument by noting that he couldn't find any evidence from scientific studies on a placebo effect in animals.
To the argument that some relief from pain from placebo treatments comes from the release of endorphins, Crislip responds by noting that in his own case involving several surgeries, he only got relief from one surgery that didn't require him to take pain killers.
I see two problems with his argument. The first I've already noted. He defines placebo effect in such a way as to exclude subjective effects from suggestion or expectation. Second, his selection of studies to review ignores those studies that have found an objective placebo effect. In my entry in The Skeptic's Dictionary on the placebo effect, I note that after the publication of the study by Hrobjartsson and Götzsche:
Dr. John C. Bailar III said in an editorial that accompanied the study: "The shoe is on the other foot now. The people who claim there are placebo effects are going to have to show it." The need, he said, is for large, rigorously designed studies that clearly define and measure effects of drugs and therapies versus placebos versus no intervention at all. These studies will have to clearly distinguish objective measurements (such as blood pressure, cholesterol levels, etc.) and subjective measurements (such as reports of pain or evaluative sensory observations by researchers, e.g., "I can see your tumor is smaller" or "I can see you are not as depressed as before").
The kind of study called for by Dr. Bailar has been done and several such studies are reviewed in chapter nine of R. Barker Bausell's Snake Oil Science (2007): "How We Know That the Placebo Effect Exists." One in particular is worth reviewing here. It was published in the Journal Pain two months after the Hrobjartsson and Götzsche article. "Response expectancies in placebo analgesia and their clinical relevance" was the work of Antonella Pollo et al. and demonstrated that placebos can help people with serious pain. The following is from their abstract:
Thoracotomized patients were treated withbuprenorphine [a powerful pain reliever] on request for 3 consecutive days, together with a basal intravenous infusion of saline solution. However, the symbolic meaning of this basal infusion was changed in three different groups of patients. The first group was told nothing about any analgesic effect (natural history). The second group was told that the basal infusion was either a powerful painkiller or a placebo (classic double-blind administration). The third group was told that the basal infusion was a potent painkiller (deceptive administration). Therefore, whereas the analgesic treatment was exactly the same in the three groups, the verbal instructions about the basal infusion differed. The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three-days treatment. We found that the double-blind group showed a reduction of buprenorphine requests compared to the natural history group. However, this reduction was even larger in the deceptive administration group. Overall, after 3 days of placebo infusion, the first group received 11.55 mg of buprenorphine, the second group 9.15 mg, and the third group 7.65 mg. Despite these dose differences, analgesia was the same in the three groups. These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects, which in turn trigger a dramatic change of behaviour leading to a significant reduction of opioid intake.
The patients who thought their IV contained a powerful pain reliever required 34% less of the analgesic than the patients who weren't told anything about their IV and 16% less than the patients who were told the IV could be either a powerful pain killer or a placebo. Each group got exactly the same amount of pain killer but their requests for the analgesic differed dramatically. The only significant difference among the three groups was the set of verbal instructions about the basal infusion. The study was too short for the differences to be explained by the natural history of recovery, regression, or any of the other alternatives found by Hrobjartsson and Götzsche.
Several things are worth noting about this experiment. The setting involves treatment being provided by medical personnel in a medical facility. This kind of setting usually involves a strong desire for recovery or relief on the part of the patient, as well as a belief that the treatment will be effective. The different verbal instructions about the basal IV would lead to different expectations. Belief, motivation, and expectation are essential to the placebo effect. Classical conditioning and suggestion by an authoritative healer seem to be triggering mechanisms for the placebo effect (Bausell 2007: 131).
Crislip would probably not be impressed and note that subjective effects and conditioning are not placebos, even if everybody else doing research in this area thinks that they are.
I also note in my entry on the placebo effect:
Martina Amanzio et al. (2001) demonstrated that "at least part of the physiological basis for the placebo effect is opioid in nature" (Bausell 2007: 160). We can be conditioned to release such chemical substances as endorphins, catecholamines, cortisol, and adrenaline. One reason, therefore, that people report pain relief from both acupuncture and sham acupuncture is that both are placebos that stimulate the opioid system.
I assume Crislip is aware of Amanzio's work, but he doesn't mention it. In his responses to his critics on his website he seems to reject conditioning as having anything to do with the placebo effect.
So, by defining the placebo effect in such a way as to exclude subjective perceptions, by ignoring studies that find objective effects from placebos, and by denying that conditioning is part of the placebo effect, Crislip is able to make his case. There is no placebo effect because he defines it in such a way as to exclude all the elements that others consider part of the placebo process.
Researchers on this subject might be better off if they ignore Crislip and take their cue from a recent study published in the BMJ: "Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome." The researchers tried to tease out the separate elements of the placebo effect. They look at three distinct components of a treatment: assessment and observation, a therapeutic ritual, and a supportive patient-practitioner relationship. It would not be surprising to find further research breaking down the effect into even smaller components. I don't think most researchers will agree with Crislip that there is no placebo effect, even if it turns out that no single component of the effect is sufficient to bring about the effect or that it is not necessary for all of the components to occur together. Nor will it matter that some of the components are also found in processes we don't usually associate with the placebo effect, such as cognitive behavioral therapy.
Hróbjartsson, Asbjørn and Peter C. Götzsche. "Is the Placebo Powerless? An Analysis of Clinical Trials Comparing Placebo with No Treatment," The New England Journal of Medicine, May 24, 2001 (Vol. 344, No. 21). Abstract.
Price, D. D. et al. (1999). An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm. Pain, Volume 83, Number 2.
Price, Donald D. et al. (2005). Conditioning, expectation, and desire for relief in placebo analgesia. Seminars in Pain Medicine. Volume 3, Issue 1. Abstract.
Several posts by Orac at Respectful Insolence and his evil twin David Gorski at Science-Based Medicine go into great detail about how CAM defenders have co-opted so-called placebo medicine.
Placebo effects are "proof" that God [sic] exists? Yes, someone has made this argument and posted it on the Huffington Post
Also, Stephen Novella, M.D., has posted this piece: American Headache Society Recommends Placebos for Migraine The placebo in question is acupuncture.
Transcript of BRAIN SCIENCE PODCAST With Ginger Campbell, MD Episode #77 Originally Aired 9/19 /2011 Interview with Fabrizio Benedetti, MD, PhD, Author of Placebo Effects: Understanding the Mechanisms in Health and Disease, and The Patient’s Brain: The Neuroscience behind the Doctor-Patient Relationship
What's in a placebo? Mike Adams certainly doesn't know "...the real difference between skeptics and pseudoskeptics is that skeptics base their skepticism on science and evidence. Pseudoskeptics like Mike Adams do not; rather, they base it in ideology.
What’s In Placebos? by Steven Novella, M.D. "A new study in the Annals of Internal Medicine reviews clinical trials over the last two years. They found that only 8.2% of clinical trials with a placebo pill as a control specifically disclosed the placebo content. Meanwhile 26.7% of trials involving injections and procedures disclosed the precise nature of the treatment."
To see the abstract of the study, click here.
Prescribing Placebos by R. T. Carroll
My review of Snake Oil Science
Placebo Effects Revisited by Steven Novella Existing evidence strongly suggests that placebo effects are mostly comprised of bias in reporting and observation and non-specific effects. There is no measurable physiological benefit from placebo interventions for any objective outcome. There is a measured benefit for some subjective outcomes (mostly pain, nausea, asthma, and phobias), but the wide variation in effect size suggests this is due to trial design (and therefore bias) rather than a real effect.
"Placebo Effect Accounts For Fifty Percent Of Improvement In Depressed Patients Taking Antidepressants" by the American Psychological Association
Irritable Bowel Syndrome: Placebo Works Even if Patients Know "Incredibly, according to a new study of patients with irritable bowel syndrome, the placebo effect, even when patients were in on the secret, worked almost as well as the leading medication on the market....After three weeks. the placebo group reported adequate symptom relief at double the rate of the group told to do nothing (59 percent vs. 35 percent). And those results are about as good as the leading irritable bowel syndrome drugs on the market. Researchers sounded the usual cautionary notes. The study was small. It's not clear what it would mean for other conditions and more research is needed."
Even so, the study supports the notion that the leading IBS medication is a placebo. Since many cases of IBS are stress-related, it makes sense that placebos would work well here if the process of administering them reduces stress. There's a lot the article doesn't cover. For a thorough analysis, see Respectful Insolence's take on this study. Or, better yet, look at the article on PLoS ONE: Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome
The magic cure "There are limits to even the strongest placebo effect. No simulation could set a broken arm, of course, or clear a blocked artery. As a rule, placebos appear to affect symptoms rather than underlying diseases--although sometimes, as in the case of depression or irritable bowel syndrome, there’s no meaningful distinction between the two. Moreover, placebos have often received undue credit for recovery that might have occurred anyway. Indeed, the effect is famously difficult to identify, measure, and even coherently define. There is debate about the magnitude of the response, with some calling it modest at best, and opposing the idea of using placebos clinically."
“Connecting with the patient, rapport, empathy . . . that few extra minutes is not just icing on the cake. It has biology.”
Placebos: Pretty Good for Depression A meta-analysis published in JAMA confirmed what several other studies have found: anti-depressants are placebos for all but the severely depressed. The authors of the study concluded: the average benefit of antidepressant medication in patients with mild or moderate symptoms of depression is minimal. "The mere act of seeing a doctor, discussing symptoms and learning about depression probably triggers the improvements many patients experience while on medication."* (See next two entries, please.)
Before You Quit Antidepressants ... The study is a so-called meta-analysis — not a fresh clinical trial....For the recent analysis in the journal, the authors identified 23 studies (out of several hundred clinical trials) that met their criteria for inclusion. Of those 23, they could get access to data on only 6, with a total of 718 subjects....That is not many studies if your goal is to answer a broad question about the efficacy of antidepressants as a class.
Study shows antidepressants useless for mild to moderate depression? Not exactly. - Science-Based Medicine - "...the paper included only 3 studies of an SSRI. How did the authors whittle down thousands of papers on SSRI effectiveness to only 3?...by using questionable exclusion criteria, the authors accessed only 3 clinically relevant studies (the Paxil studies), involving only one SSRI. It is not clear that these studies are representative of existing studies on SSRIs, or even if they can be generalized to other SSRIs." (See also Science by Press Release.)
German study on the placebo effect hyped by mediaThis is about a report in Science. The study had only 15 participants, all men. It involved doing an fMRI of their spinal columns while applying different degrees of heat to their arms, which had been treated with an analgesic or a placebo. Some of these stories seem to think the study is groundbreaking because it shows that the placebo effect is not all in the head. We already knew that from numerous studies. Some claim that the study proves spinal inhibition is one of the mechanisms by which the placebo effect reduces pain. No, it doesn't. The study is too small to prove anything. It needs to be replicated with larger groups and with some extensions to make sure the fMRI readings are caused by the placebo and indicate what the researchers think they indicate.
A Doctor for Disease, a Shaman for the Soul Mercy Medical Center in Merced figured it was healthier to bring them in rather than shut them out, so it invited the many Hmong shamans who dwell in California's central valley to learn about medicine in exchange for allowing the shamans to treat spirits in the hospital. Superstition and science work hand-in-hand in more than 60 hospitals in the United States in an effort to accommodate cultural beliefs and break down barriers that keep many people from seeking treatment for their serious health problems.
Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why. By Steve Silberman. Wired. 24 Aug 2009. [The article is worth reading but the blinking ad on the right might drive you away. Shrink your viewing window to block out the annoying ad.] First, the facts: an increasing number of new medications are unable to beat sugar pills in RCTs (randomized control studies); trials done in different cultures get different placebo responses; and those of us subjected to constant advertising of pills for every ailment under the sun packaged with stories from satisfied customers are being conditioned to expect relief for our ailments from a pill. It is, of course, possible that the effectiveness of new drugs versus placebos is decreasing because the clinical trials are getting better or the new medications are less effective. There have been studies that have found that certain persons are more susceptible to placebos than others. What is intriguing is that there has been very little study on the cultural influences that affect placebo response. More intriguing is the role of cultural conditioning on susceptibility to placebo effect. Though some laugh at the idea of the placebo effect increasing, it is possible that through social conditioning more and more people could become more affected by placebo medicine (including the theater, the suggestions, and all the other things that are lumped together under the 'placebo effect').
Placebo medicine to be offered by NHS in Northern Ireland Homeopathy, acupuncture, and reflexology are among a range of placebo therapies a new trial concludes should be provided by the NHS. "As many as 81% of patients receiving the treatments on referral from their GP reported improvements in their physical health, and 79% in their mental health." It will save money, too.
The placebo effect is the healing force of nature by G. Zajicek
The Placebo Prescription - New York Times Magazine 1/09/2000
Sham Surgery Returns as a Research Tool by Sheryl Gay Stolberg, New York Times 4/25/1999
A surprisingly potent placebo: face time with me by Dr. Michael Evans
Researchers Debunk Placebo Effect, Saying It's Only a Myth by Gina Kolata (NY Times)
Last updated 08-Jun-2015