Placebos |
by:
Foley, Frederick
|
THE meaning that placebos have
had for health care providers has swung like a pendulum through the ages - from magical cureall to disparagement to a current hard look at the biological and psychological aspects of this phenomenon.
What exactly is their status in today's medical and research world? The word placebo derives from the Latin term "to please." The concept of a placebo comes from medieval times, when professional mourners were paid to stay by the bedside of. deceased person, reciting a psalm beginning "Placebo Domino..." or "I shall please the Lord." "Placebo" gradually became the word used for the paid mourner, whose grief was, in fact, false.
In modern medical terms a placebo has come to mean "the psychological, or psychophysiological effect of any medication or procedure given with therapeutic intent, which is independent of, or minimally related to, the pharmacological effects of the medication or to the specific effects of the procedure, and which operates through a psychological mechanism." In medicine a placebo is an inactive substance given to a patient which appears to bring benefit, but has no direct effect on a disease process. Its positive effect is psychological or non-specific (that is, there is no direct causal link between the treatment and the disease outcome).
Let us briefly consider two scenarios: Susan S. has heard through the grapevine about a new dietary supplement that some people say helps MS. When she talked to her doctor, she learned that the supplement had been tested thoroughly and showed no actual benefit for the disease. Nonetheless, because some people claimed it worked for them, and because it was clearly safe and inexpensive, she gave it a try. For a short time, the dietary supplement actually helped her to feel better. John C. has been offered a place in a clinical trial for a new drug treatment for MS. His doctor has told him that the study will be a well designed, controlled and blinded experiment, and that John has a 50-50 chance of receiving the active drug or a "sham" treatment which is being tested for comparison. The rate of progression of John's MS slowed down briefly after he started the drug so that he was surprised when he later found out he was in the placebo group. What both John and Susan are experiencing, in different ways, are aspects of the placebo effect:
It is an intriguing phenomenon that has both admirers and critics and its roots go way back in history.
The history of placebo in
medicine
How do placebos actually work?
Most is known about how the placebo effect works biologically
in alleviating While the pain analogy may not be directly related
to what happens in MS
More indirect information comes from conditioning experiments classical psychological studies in which the body is "taught" to respond biologically to certain mental states. The historical roots of how behavioral and physiological responses can be conditioned derives from the work of Dr. Ivan Pavlov. Pavlov discovered that dogs can be trained to salivate to the sound of a bell. By repeatedly pairing the sound of a bell with the presentation of food, the dogs eventually learned to salivate- the biological response - in the absence of food, whenever the bell was sounded. Thus, the physiological response of salivation was conditioned to the sound of the bell. More recent research on conditioning shows that many biological responses can be changed through conditioning, such as blood pressure, heart rate, and even immune responses, as noted previously. The ability to condition immune responses in animals and perhaps in humans may have implications for understanding how placebo expectation - psychological phenomena - can affect disease.Conditioned suppression of immune responses has been shown since 1974, following a serendipitous discovery by a psychologist who was studying how quickly mice can learn to avoid drinking water which is flavored with something associated with nausea- in this case, nausea induced by the drug cyclophosphamide (an anti-Cancer agent, which by coincidence is sometimes used to try to arrest progressive MS).Dr. Robert Ader, a psychologist at the University of Rochester, paired the taste of saccharine-flavored water with an injection of of nause producing cyciophosphamide. While cyclophosphamide produces nausea,it also is a potent short-term suppressor immune system function. which can be easily demonstrated by laboratory analysis of immune activity.Dr. Ader found to his surprise that, after a period of training, animals that had been conditioned with saccharine and cyclophosphamide over several test periods actually showed Immunosuppression even in the absence of the cyclophosphamide treatment when given saccharine alone. The animals had somehow "learned" to associate the flavored water with Immunosuppression which had resulted from drug delivery; over time, the drug delivery wasn't even needed !In a related phenomenon, it has also been shown that people with severe hay fever can "learn" to react with bona fide symptoms of their allergies simply by being shown pictures of hayfields! A conditioned allergic response clearly is occurring, since the pictures themselves cannot have elicited the symptoms.Although the mechanisms for this type of conditioning are not understood, it is clear that life forms as simple as single-ceiled animals or as complex as human beings are capable of being conditioned. Perhaps the magic of the placebo effect can in part be explained by the body's responding biologically in conditioned fashion in the right set of circumstances.
The placebo effect in MS clinical
trials
Among the earliest well-designed clinical studies of
MS in the 1960's examining A recent In Multiple Sclerosis, the placebo effect is more problematic
than with many So I think MS, more than any other disease I can
The origin of the placebo
effect in clinical trials
Dr. Hauser agrees: "I think it stems from the psychological
belief that you're
Can the placebo effect be
used to help?
In 1974, Norman Cousins published a now-famous account
of his recovery from a His Although reports by Cousins and others have generated
public interest and
It is important for researchers, physicians and, above all, patients to approach this point of view with extreme caution. It can cause guilt and unnecessary distress because it induces the misconception that the individual with MS is responsible somehow for acquiring MS or for the progression of the disease. The fact is, it is not known if the mind or one's mental state can influence the underlying disease process in MS, or what the hypothesized mechanisms of this interaction would involve. It is known that MS happens to people with every conceivable mental state and personality type, and persons of all intellectual and socioeconomic levels. Similarly, it is not known why some people get more severe cases of MS than others, but severity of illness seems to be completely independent of psychological state.This caveat aside, the answer to the question, "Can the placebo effect be used to help?" Is "yes and no," because in fact the placebo response in the treatment of illness, and especially MS, remains shrouded in mystery. Some view it as a phenomenon that must be overcome in the evaluation of new therapies for efficacy and safety while others view it as a reservoir of hope, in that we may some day penetrate the mystery and gain a clearer understanding of the ways in which the mind may have an impact on illness.Probably both perspectives are appropriate and deserve continued attention. Although it is clear today that psychosocial and "placebo" factors play a role in how one adjusts to living with MS, it is just as clear that placebo effects are too short-lived and incomplete to provide meaningful treatment for a disease like MS. However, how psychological factors- placebo effects may work in conjunction with new biologically targeted treatments is an open question. Perhaps present and future research will be able to gain more knowledge on the key questions: Does the mind influence MS; what is the nature and extent of the mind's influence; what are the mechanisms involved; and finally how can the mind be used in a truly comprehensive treatment plan for people with disease?
Placebos Questions Often Asked
Is it possible to self-induce a placebo effect? Placebo effects are always self-induced by the belief that one is taking a helpful remedy or procedure. Without this conviction, a placebo effect will not occur. The question sometimes is raised, however, "If you know that it is an ineffective medication, can it still help you?" It is difficult to see how someone could know that what he or she was taking was a placebo and still benefit from it. The knowledge that one is taking an ineffective treatment is incompatible with what is required to generate a placebo effect. What's the difference between a quack remedy and the placebo effect? Quack remedies and placebos both have something in common. There is no causal link between the "treatment" and the disease outcome. However, more deception is present with the administration of "quack" remedies, in that promises and claims of efficacy are made directly without scientific justification. When aphysician prescribes a placebo, it is anticipated that it will bring short-term relief to some condition for which there is no other established treatment. In clinical trials, placebos arc administered with the permission and knowledge of participants (even though no one knows which subjects received the placebo).The purpose of administering placebos is to obtain knowledge about treatment effectiveness in a scientific study. The purpose of administering a quack remedy is to deceive for profit.Since the placebo effect can have real biological impact, is there any way to extend the placebo effect? Placebo effects tend to be self-limiting. If a person with MS were taking a placebo and "felt better," then experienced an exacerbation, the belief that the placebo was helpful would be sorely challenged in most cases. Even if placebo effects were present, they would be difficult to sustain over time. Perhaps in the future we will learn to "manipulate" placebo effects so they can be helpful in MS.
Dr. Frederick Foley, an associate professor of psychology at Yeshiva University, has been investigating the relationship among mental states, clinical symptoms, and the immune system in MS for the last eight years. His studies have been based on both people with MS and mice with an MS-like disease.
National Multiple Sclerosis Society 733 Third Avenue New York, NY 10017-3288 (212) 986-3240 INSIDE MS Spring 1993 Volume 10 No.2, p
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