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Alternative Medicine
Is It All in Your Mind?
Francisco A. Tausk, MD
Arch Dermatol. 1998;134:1422-1425.
ABSTRACT
Therapeutic interventions may trigger nonspecific mechanisms whose effects are not attributable to the specific properties of a given treatment. Recent investigations on the placebo effect as well as other mind-body interactions are helping us to understand some of the underlying mechanisms, as well as beginning to provide us with potentially effective adjuvant treatment strategies for a variety of human diseases.
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Alternative medicine represents practices neither incorporated into the mainstream of Western medicine nor validated by traditional scientific instruments, such as double-blind, controlled trials. Notwithstanding this vague definition, many of these medical approaches are widely used by mainstream practitioners in other parts of the world, as, for example, is the case of acupuncture or herbalist medicine in Southeast Asia; thus, the alternative label partly results from cultural variables. Some of the drugs that we prescribe in dermatology lack strong scientific proof of efficacy, and yet we do not consider ourselves alternative practitioners for using them; thus, the traditional or alternative labels may be a result of our particular training. Many alternative modalities are currently classified as "mind-body interactions," and within this category we find the placebo effect.
For the last 30 years, the US Food and Drug Administration has required that to consider the beneficial effect of a drug, it has to be significantly more effective than a placebo. It is widely accepted that the specific effect of a drug or therapeutic modality is accompanied by nonspecific effects that may influence positively or negatively the outcome of the therapy. Studies that compare a drug with an inert substance are trying to determine how much of the effect is due to the drug itself, and how much is due to the natural history of the disease, expectancy, and psychological influences such as participating in a study, or believing that the subject is being administered a medicament. The effectiveness of a drug will derive from mathematical formulas that will depend on large differences between studied groups, or small changes in a large number of participating subjects. However, some health care providers and many patients are not overly concerned with the levels of statistical significance of outcome measures. In 1990, there were more visits to alternative medicine practitioners than to all primary care physicians combined, resulting in an expenditure of $13.7 billion, and most of these patients were concealing these visits from their regular physicians.1 Similar trends have been reported elsewhere, such as in the case of Australia, where nearly 50% of the population consults alternative practices.2 The use of a particular therapeutic modality by large numbers of individuals does not by itself validate it, but is suggestive of some perceived benefit. Since most alternative practices are based on principles that we currently do not fully understand, without the appropriate formal scientific studies we cannot differentiate their effects from placebo (understanding placebo as a therapeutic modality that does not have any specific effect in the treatment of a given disease). The effectiveness of placebos is difficult to evaluate. Since the initial studies in the 1950s,3 suggesting that approximately 30% of the effect of therapies is due to placebo, numerous studies have examined this phenomenon. When we analyze the results, we are confronted by the observation that there is a marked variability in the reported effectiveness of the placebo arm. This is true of studies that measure the effects of the same drug, for the same disease, with a similar study population and similar protocols. Given all the conditions being equal, we have to assume that the differences seen in placebo response are due to the way they are administered. Critical to this is the manner in which the subjects' expectations are influenced by the transmittal of unconscious cues, reinforcing their belief or disbelief in the effectiveness of a particular medical intervention. In support of this is the notion that most patients participating in studies are anxious to identify if they are in the active or placebo arm of the study. Similarly, expectancy plays an important role in the outcome resulting from a placebo. Recently, Roberts et al4 examined medical and surgical procedures that were widely used in the past, and were later abandoned following placebo controlled studies that showed their lack of effect. These authors carefully examined the data obtained from open studies at a time when they were considered highly effective by the patients as well as their physicians. They analyzed the use of glomectomies as treatment for asthma, levamisole as an immunomodulator, photodynamic therapy and organic solvents for herpes simplex infection, and gastric freezing for ulcers. Seventy percent of the almost 7000 patients who participated in these open studies in the 1960s and early 1970s were found to have obtained good to excellent results from these modalities. This report shows that belief and expectancy of patients, and especially of their health care providers, played a critical role in determining the effectiveness of treatments later found to be nonspecific by scientific measures.
The notion that the mind can affect overall health is not new. Although for many years the nervous system, immune system, and animal/human behavior have been the subject of individual study, new lines of research are now emerging that examine the interrelation between these seemingly disparate disciplines. During the last 2 decades it has become clear that numerous neuropeptides, neurotransmitters, and neurohormones not only exert effects within the neuro-endocrine systems but are also capable of augmenting or impairing the immune response by directly binding to specific receptors on the surface of immune cells.5-6 Thus, not only are lymphoid organs innervated by noradrenergic postganglionic sympathetic fibers7 but also the products released from peptidergic neurons have a distant effect on cells of all tissues. For example, mediators such as substance P, calcitonin gene-related peptide, somatostatin, corticotropin, vasoactive intestinal polypeptide, neuropeptide Y, among others, have a profound effect on inflammation in the skin through their effect on local keratinocytes, mast cells, Langerhans cells, and blood vessels and local and distant lymphocytes, neutrophils, and macrophages.8-9
"Most of our knowledge about how the brain links body memory and emotions has been gleaned through the study of classical conditioning."10 In this process, for example, a rat perceives a noise that is paired to an electric footpad shock, and after a few such experiences (training), the rat responds automatically to the sound in the absence of shock. The noise is the conditioned stimulus, the foot shock the unconditioned stimulus, and the rat's reaction is a conditioned reaction, which consists of readily measured behavioral and physiological changes.10 Early evidence of this mind-body connection stemmed from Pavlov's landmark classical conditioning studies in dogs, pairing the sound of a bell to the presence of food.11 Contemporaneously, Metalnikov and Chorine12 reported classical conditioning of the immune system in guinea pigs. The latter studies were mostly ignored until the 1970s, when Ader et al13 and Cohen et al14 showed classical conditioning of immunity using cyclophosphamide and saccharin as the unconditioned and conditioned stimuli, respectively. Cyclophosphamide was paired with saccharin, and the trained animals were later exposed to saccharin alone, which evoked identical immunosuppressive effects as those produced by the cyclophosphamide. Since then, numerous studies15-17 have shown the effect of conditioning to suppress or enhance the immune response. Classical conditioning in humans is a well-recognized phenomenon, as exemplified by anticipatory nausea in patients with cancer receiving chemotherapy18; however, conditioning of immunity in humans has never been shown. This may be partially explained by the need of a strong and novel conditioned stimulus that is administered isolated from other environmental cues, and the difficulty in delivering this in humans because of the critical nature of our awareness.
IN THE LAST 20 years numerous human studies have shown the influence of psychosocial factors on the immune system,19 such as the presence of stress as a determinant in the development of the common cold following inoculation of the virus to healthy volunteers.20 Even the evolution of neoplastic diseases has been found to be influenced by these factors. Spiegel et al21 reported that women with metastatic breast cancer, who in addition to their standard treatment participated in a weekly session of group therapy and hypnosis, had a mean survival time that was double (36.6 months) that of a control group only receiving the standard oncological treatment (18.9 months). Fawzy et al22 found a significant increase in survival of patients with metastatic malignant melanoma who participated in weekly psychiatric group sessions for 6 weeks, compared with those who did not. Hypnosis, as a psychological intervention, has been demonstrated to effectively modulate inflammation of the skin23-28 and has been reported in uncontrolled or anecdotal studies to modify the clinical outcome of human disease,29 including cutaneous disorders such as eczema,30 urticaria,31 warts,32-33 and psoriasis.34 We recently proposed the use of hypnosis as a tool to provide changes in the immune response in humans, in a manner similar to or replacing the effect of placebos, suggesting that hypnosis may allow us to bypass the natural human critical ability and simultaneously magnify the stimulus administered.35 Hypnosis is a set of procedures during which suggestions are given for distortions of perception or memory; understanding suggestion as an idea offered to a person for uncritical acceptance.36 In a recent randomized controlled pilot study35 we showed the significant improvement (mean, 85%) in the psoriasis activity score index (PASI)37 in highly hypnotizable patients with psoriasis subjected to weekly hypnosis. A sizable population of patients could benefit significantly from nonspecific treatments, not only because of their effectiveness but also because of the added benefit of limited adverse effects.
When analyzing results of clinical drug studies, we many times observe that patients on the placebo arm of the study have a positive response. In studies that show figures with all of the subjects' data, we sometimes find that a number of the placebo responders have results similar to those of the active drug, whereas others show no improvement, or what is more common, further deterioration of the disease being treated. This supports the notion that in a number of diseases, some of the placebo responders do well with nonspecific treatments. Most results of drug studies are reported as overall means of the active vs placebo arms. In this fashion, the results obtained from the placebo group are averaged between those who responded well and those who (as expected) continued to deteriorate, and only when the responder group shows impressive results do the mean values show significant improvement. However, it is difficult to examine this further, since the data of individual subjects are not readily available from pharmaceutical companies and this information is denied by the Food and Drug Administration, based on the provision in the Freedom of Information Act that exempts trade secrets and confidential commercial information from public disclosure.
More difficult than identifying the effects is understanding the underlying nature of placebos (reviewed by Kirsch38). Multiple explanations attempt to justify the effect of nonspecific treatments on patients. One obvious explanation lies within the natural evolution of diseases, and their waxing and waning independently of the therapeutic interventions. Many a practitioner becomes a patient's champion because he/she provided the last intervention before the symptoms improved spontaneously. Deception and self-deception or demand characteristics of the situation do not usually play a role in dermatologic studies, since the results are usually measured by a validated instrument and not self-reported. Participation in clinical trials may provide some degree of comfort, decrease in stress and anxiety, as well as patient education and contact with other patients with similar conditions, which may play a role in reduction of symptoms. The constructed belief that a result will occur, or expectancy, as well as classical conditioning play a role in defining a placebo response and are difficult to differentiate from one another in some situations.
Although we do not fully understand the power of placebos, we should begin to harness their use. Recently, Nickel39 reported that in a large trial of a drug to reduce benign prostate hypertrophy, subjects in the placebo arm of the study, as expected, suffered an increase in prostate size; surprisingly, however, they experienced marked improvement in the symptoms as well as in the objective measurements of urinary flow. Interestingly, these patients also experienced adverse effects, and 13% of the subjects had to discontinue the placebo because of the latter. This observation, which suggests that placebos may reduce the subjective as well as objective signs and symptoms, without tissue-specific anatomical modifications makes us rethink our therapeutic goals. Would it be useful to provide symptom relief through nonspecific therapies? Can we combine specific and nonspecific treatments to augment their efficacy? If so, it is important to identify modalities that provide such treatments in an ethical manner without deceiving the patients. Hypnosis has been proposed in the past as a nondeceptive technique for the provision of placebo in psychotherapy.40 Our current interest is directed toward assessing and understanding the potential efficacy of hypnosis, classical conditioning, and a combination of both in the provision of nonspecific therapies to patients with dermatologic diseases. However, nonspecific effects are also exploited by some practitioners to deceive patients into believing in the putative-specific effect of certain treatment modalities. It is, therefore, crucial that when evaluating the effect of traditional as well as alternative therapies we apply strict scientific methods to measure their validity.
AUTHOR INFORMATION
Accepted for publication June 30, 1998.
Reprints: Francisco A. Tausk, MD, Department of Dermatology, Johns Hopkins Outpatient Center, 601 N Caroline St, Baltimore, MD 21287-0900 (e-mail: ftausk{at}welchlink.welch.jhu.edu).
From the Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Md.
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