A placebo is generally defined as “an inert medication used for its psychological effect, or for purposes of comparison in an experiment,” the latter usually referring to the performance of a controlled study to determine the efficacy of a new treatment. In this latter situation, the placebo, i.e., an agent that exerts no physical effect on a disease, is identical in form to the active agent, and is usually provided to equal numbers of recipients with a given illness in order to ascertain whether those receiving the “active” treatment show more benefit than those receiving the placebos. When possible, to avoid biasing the results, these studies are “double-blinded”, meaning that both those administering the treatments and those receiving them are unaware of who is receiving the active agent.
The placebo effect can be defined as any improvement or change in subjective discomfort or illness not explained by the effect of the treatment given. I have deliberately broadened the definition to include unconventional methods of treatment, such as that provided by faith healers and, for the most part, practitioners of various forms of alternative medicine. The placebo effect also plays an important role in the daily practice of medicine for almost all conventional medical caregivers.
Few people outside—or inside—the medical profession fully understand the power of the placebo effect. It has been aptly characterized as “something to control in clinical research, something to cultivate in clinical practice, and something present in all healing encounters.” Although not well understood, the mechanism of the placebo effect relates to the power of the mind to affect bodily sensations and functions. It is especially effective in relieving pain, anxiety, fatigue, insomnia, and depression, but can go far beyond these to enhance the effectiveness of medical treatments with acknowledged physical benefits. With this expanded definition we can review some of the vast experience with this phenomenon, and lessons learned, over the past half century.
Based on a review of medical studies, placebos improve or relieve symptoms in a widely divergent percentage of individuals suffering from numerous medical conditions. But the cause for such variable responses depends on the type of illness treated, the context of its administration, and how long the subjects are observed. For instance, when used to evaluate new drugs, researchers focus solely on the difference between the active drug and the placebo, and so the placebo effect itself is rarely analyzed or compared with an absence of treatment. Compared in this latter way, one study reported little difference between a placebo and no treatment; however, this information was tempered by the inclusion of numerous physical diseases and did not evaluate the nature of the interaction between caregiver and patient. Pain, however, did show a significant placebo response when compared with no treatment.
Generally, subjective symptoms unrelated to serious underlying organic diseases, such as pain or fatigue, are the most likely to be relieved by a placebo. That is not to say, however, that these symptoms are simply imaginary and not actually felt. I believe the relief of symptoms in this context is real, but the underlying physiological mechanisms are not well understood. A beneficial response occurs most often when the treatment is provided by a caregiver who explains that s/he expects improvement. It is also most likely to occur in individuals who are, in general, highly receptive to suggestion. Additionally, the responses are more profound when a given medication is thought to be more expensive than a cheaper one., an effect likely transferable to all types of treatment.
Perhaps the most potent placebo effects result from physical interventions, such as acupuncture. Recent studies have shown marked improvement with either traditional acupuncture, or a sham which employs superficial needling at non-acupuncture points. For example, in a trial of over 1,100 patients with chronic low back pain who received ten 30-minute sessions over five weeks, the improvement rate after 6 months was 48% for traditional acupuncture and essentially the same for the sham procedure, compared to 27% for patients receiving customary care (physiotherapy plus as-needed pain medication), clearly confirming the placebo effect. The same observations have been found with migraine and tension-type headaches (formerly called tension headaches), irritable bowel syndrome, chronic low back pain, and even arthritis of the knee.
These findings establish two important points; the sham acupuncture is as effective as the real procedure, qualifying both as effective placebos, and the efficacy of both real and sham acupuncture procedures far exceeded those of ordinary medical management, indicating that the placebo effect is powerful indeed. These and many other similar trials strongly suggest that acupuncture, a procedure that involves an elaborate treatment ritual with close caregiver-patient interaction, provides the basis for a maximum placebo effect. Thus physical manipulations, as exemplified by acupuncture and probably chiropractic treatment, demonstrate more profound beneficial effects than do orally administered placebo tablets.
A recent study involving patients suffering from irritable bowel disorder reinforces the importance of personal interaction in any treatment encounter. Recipients of treatment were divided into three groups, the first two receiving sham acupuncture twice a week for 3 weeks. In the first group, there was a 45-minute conversation with the practitioner at the initial visit regarding the patient’s condition and positive expectations of successful relief; in the second group, initial communication between practitioner and patient was businesslike and limited to 5 minutes, although presented with the idea of likely relief from acupuncture therapy. A third group received no treatment. At three weeks after the “treatment”, 62% of patients in the first group reported adequate symptom relief, compared with 44% in the second group, and 28% in the third group. This experiment indicates that, when enhanced by supportive communication, the placebo effect is most dramatic.
Recognizing that the placebo effect is so closely bound to interpersonal contact, Kleinman et al. advocate an informal process of medical psychotherapy as a basic component of care, focusing on the experience of chronically ill patients: “It is of the utmost importance that physicians achieve the highest possible placebo effect rates. To do this, doctors must establish relationships that resonate empathy and genuine concern for the well-being of their patients.” They add that “The chief sources of therapeutic efficacy are the development of a successful therapeutic relationship and the rhetorical use of the practitioner’s personality and communicative skills to empower the patient and persuade him toward more successful coping”.
Sham surgeries have also demonstrated dramatic placebo effects. For instance, in the 1950s, a common belief held that individuals suffering from angina pectoris (chest pain originating from the heart) could benefit from the surgical ligation (closure) of arteries supplying the chest wall (the internal mammary arteries). This idea was based on the assumption that the procedure could divert blood flow to more critical locations, i.e., the heart. Because of the tenuous nature of this hypothesis, a group of researchers divided 18 volunteer individuals into two groups. Half received the ligation procedure, and the others received only superficial incisions on chest without ligation. None of the participants was aware of which treatment s/he received. Surprisingly, both groups experienced marked, equal improvement in their symptoms. Of the entire group, fifteen experienced total relief of their symptoms after the procedures, and this relief persisted for periods up to one year. Very shortly after this study was published in 1960, this procedure was discredited and abandoned, but the experience lent strong support to the concept that the placebo effect was indeed powerful.
The interaction between mind and body is so potent that it can affect the course and outcome of certain organic, or physical, diseases. Mental depression is a well-known cause of poor outcomes in patients who have suffered myocardial infarctions (heart attacks). The cause of this relationship is not well understood. In those who suffered an attack, treatment with antidepressant drugs has been found to improve not only quality of life but also probably reduces recurrent heart attacks and even mortality, although the data are currently too limited to enable a firm conclusion. Since depression often responds profoundly to placebos,, this suggests that the placebo effect could even be lifesaving.
The placebo effect may be beneficial in physical conditions as Parkinson’s disease, asthma, and duodenal ulcer and inflammatory gastrointestinal conditions. Although placebos have no effect on progression of cancer, they have been found to reduce associated symptoms of pain, loss of appetite, anxiety, and depression.
As one might anticipate, the placebo effect influences erectile dysfunction (ED). In a large analysis of Viagra versus placebo, Viagra was 57% effective in promoting successful sexual intercourse and a placebo resulted in a 21% success rate. One humorous response to this data is a suggestion that men should try the placebo before using Viagra, for it could at least save money.
Of the manifold responses to the placebo, what is perhaps most amazing is its effect on physical sports performance! Enhancement of performance has been demonstrated in several trials. Clark et al provided one notable example, when they studied the endurance of 43 cyclists in a 40 kilometer timed trial. After suitable allocation into subgroups, those given placebos that were told they had received performance-enhancing carbohydrate performed 3.8% better than those given the same drink but told it was a placebo. Similar observations have been made in studies of muscle endurance and power in other athletes. This raises the intriguing—albeit facetious—question: Should the administration of performance-enhancing placebos be considered “doping”, and worthy of disqualification from competition?
. Since placebo effects are influenced by the interplay between recipient and caregiver, the personality and mannerisms of the latter strongly influence the results. Some physicians likely obtain optimum results by having a placebo personality—a positive and upbeat attitude toward an expected successful outcome. Additionally, of all patients seen in most general clinics, I would estimate that approximately 50%–70% have self-limiting conditions that will improve or resolve without treatment. This means any action taken by a caregiver will usually be followed by a favorable outcome and, according to the so called post hoc fallacy, both the patient and caregiver may be seduced into believing the treatment brought about subsequent improvement. Thus, all practitioners, legitimate or otherwise, will achieve success through a combination of natural outcome, placebo effect and post-hoc reasoning. This can easily account for the apparent success of practitioners of various forms of alternative medicine and faith healing.
The mechanism for the placebo’s influence on brain/body connection had always been obscure until clues began to surface in the 1970s. The discovery of substances produced by the brain, called endorphins, has provided one possible answer to this enigma, at least with regard to the role of the placebo in combating pain. Endorphins are chemically similar to opiates like morphine and, therefore, likely provide pain relief. But does the placebo stimulate the brain’s production of endorphins? The answer is they probably do, for one study demonstrated that Naloxone, a drug that blocks the physical effects of morphine, also was capable of nullifying relief of pain that was attributable to the placebo effect. This may account for some of the real and physical pain relief afforded by placebos.
Since most standard medical caregivers are keenly aware of the placebo effect, it is not surprising that this principle would be applied in clinical practice. Placebos may be administered in a “subtle” form, wherein a barely effective medication (such as a mild tranquilizer) is given together with strong reassurance that said nostrum will be effective. Highly attenuated preparations are said to be “homeopathic” in nature, which is simply a form of alternative medicine. Probably less often, a medication without any physical effect whatever may be delivered with the same fanfare. Actual surveys of practitioners in mainstream medicine confirm the widespread use of placebos: in a study by Nitzan and Lichtenberg, 60% of physicians and nurses used placebos, usually as often as once a month or more, and in most cases the patients were told they were receiving “real” medication. Of this latter group, 94% reported they found placebos generally effective. Another survey among academic physicians in the United States disclosed that 45% had used placebos in clinical practice, most commonly to reduce anxiety and as supplemental treatment for physical problems. As many as 96% of these physicians believed placebos can have therapeutic effects, and 40% reported placebos could even benefit patients’ physical problems. These studies serve to add additional support garnered worldwide from earlier surveys showing the same overall findings. Very few practitioners in any of these surveys considered placebo-giving as immoral or worthy of prohibition. Regardless of one’s opinion about this issue, however, the placebo’s safety profile is absolutely unbeatable!
How do the differing forms of placebo compare?
One recent study analyzed the relative power of differing methods of administering placebos against each other, and the answers were quite consistent with the above discussion.
The review to which I refer studied the various means of managing sufferers of migraine headaches, and it confirms and brings all the above concepts into sharp focus. These investigators, by pooling large numbers of previously performed individual trials, sought to compare obvious placebo medications and procedures with one another. They compared the efficacy of the following placebos for their ability to reduce the number of migraine headaches: 1) An oral placebo (fake) pill identical to an active medication, 2) Sham acupuncture, consisting of superficial needling at nonacupuncture points, 3) Sham injections of inert agents, 4) Sham surgeries, consisting of small incisions in various locations of the body without any organ or tissue manipulation, and 5) Miscellaneous sham procedures such is exposure to electromagnetic devices.
If there was a reduction of headache frequency by at least 50%, subjects were judged to be “treatment responders.” Not surprisingly, the percentages of responders in each group receiving a placebo were as follows: Sham surgery showed a 58% response rate, sham acupuncture, a 38% rate, and placebo pills, a 22% rate. The remaining miscellaneous procedures showed response rates no different than those of the placebo pills. Thus the placebo effects were clearly greater in conjunction with those procedures employing hands-on contact with subjects. Somewhat surprisingly and inexplicably, however, they found no significant difference between sham injections and placebo pills, but this finding was at variance with previous studies that did find that injections possessed more potency.
Science has progressed greatly over the past century, notably in biology and medicine. Through its methods we have forged a new path into disease prevention and treatment, which can shed light on the mechanism of apparent benefit provided by obviously worthless remedies. Each person is usually primarily interested in obtaining relief from a symptom or disease. When apparent improvement follows a given intervention, one often attributes the result to the preceding act, which represents not only a potential post hoc error but also lack of understanding of the placebo effect, as well as the fact that most illnesses will improve or resolve with time in the absence of treatment. Faith healers and those providing “miracle” alternative treatments take advantage of these same principles, often to great financial gain. Even many of us in conventional medical fields can intervene in some way—by pill or procedure—then may claim credit for the subsequent improvement or cure.
Although most of our treatments are supported by scientific rationale, we often have no way of separating physical from placebo effects. The best advice I can provide the public is to maintain healthy degree of skepticism with regard to issues of health and apparent “responses” to treatments.
I might simply conclude that similar to the case of atomic energy, our challenge is to learn how to harness the power of the placebo for good rather than for evil!
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