The Placebo Response: Recent Research and Implications for Family Medicine

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Original Research

The Placebo Response: Recent Research and Implications for Family Medicine

J Fam Pract. 2000 July;49(7):649-654

By

Howard Brody, MD, PhD

The placebo response is commonly invoked as a factor in the therapeutic relationship between the family physician and the patient, but important recent literature can be difficult for family physicians to access. Coordinated interdisciplinary research into the placebo response as it occurs in primary care settings is lacking.

Although there is controversy about the nature and scope of the placebo response, important suggestions are emerging about its psychological mechanisms (expectancy and conditioning) and the biochemical pathways that act as psychosomatic linkages (endorphins, catecholamines and cortisol, psychoneuroimmunology). The available research justifies interventions by family physicians that maximize the placebo response in everyday patient encounters. These include the sustained partnership approach, working with patients on the narratives they construct to explain illness, listening to patients, providing them with satisfactory explanations, expressing care and concern, and enhancing their sense of control. Notable opportunities exist for family medicine investigators to expand the understanding of this phenomenon.

References

1. Berg AO. Placebos: a brief review for family physicians. J Fam Pract 1977;5:97-100.

2. Freeman TB, Vawter DE, Leaverton PE, et al. Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson’s disease. N Engl J Med 1999;341:988-92.

3. Macklin R. The ethical problems with sham surgery in clinical research. N Engl J Med 1999;341:992-96.

4. Hróbjartsson A. Placebo intervention: what is its clinical effect? Presented at the conference, Complementary and alternative medicine: the scientific and pluralistic challenge, Boston, Mass, December 10, 1999.

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7. Berg AO. The placebo effect reconsidered. J Fam Pract 1983;17:647-50.

8. Tudor Hart J. Caring effects. Lancet 1996;347:1606-08.

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10. Hahn RA. The nocebo phenomenon: scope and foundations. In: Harrington A, ed. The placebo effect: an interdisciplinary exploration. Cambridge, Mass: Harvard University Press; 1997;56:76.

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14. Roberts AH, Kewman DG, Mercier L, Hovell M. The power of nonspecific effects in healing: implications for psychosocial and biological treatments. Clin Psychol Rev 1993;13:375-91.

15. Kleijnen J, de Craen AJM, Everdingen JV, Krol L. Placebo effect in double-blind clinical trials: a review of interactions with medications. Lancet 1994;344:1347-49.

16. Brody H. Placebos and the philosophy of medicine: clinical, conceptual and ethical issues. Chicago, Ill: University of Chicago Press; 1980.

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18. Greenhalgh T, Hurwitz B, eds. Narrative based medicine: dialogue and discourse in clinical practice. London, England: BMJ Books; 1999.

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Since the placebo response was last reviewed for family physicians¹ new research has added to our basic knowledge of this phenomenon, but placebo research remains in its infancy. Outcome studies have shown how various physician behaviors and practice styles can enhance the health status of patients. Seldom, however, are these 2 bodies of research carefully integrated to show the clinician how to best use the science of the placebo response to improve patient outcomes. Such integration is possible and would be useful for family physicians.

The science of the placebo

Two recent findings highlight the continued controversy over the placebo response. The apparent importance of the placebo response was recently emphasized by the ethical debate over the use of sham surgery control groups in studies of fetal cell brain implants for intractable Parkinson’s disease.^2,3 The need for a sham group and the ethical question of whether exposing subjects to this risk is warranted arises because subjects receiving the sham procedure typically exhibit marked improvements in their Parkinson’s symptoms for up to 6 months and are indistinguishable from patients given the active treatment. This improvement does not seem to be due to either the natural history of the disease or observer bias.

However, the preliminary findings from a carefully conducted meta-analysis⁴ failed to demonstrate any consistent sizeable benefit from receiving a dummy treatment in a randomized blinded trial when another nontreatment group was included with which the sham-treatment group could be compared. These findings do not exclude the possibility that the psychosocial aspects of the physician-patient encounter may exert independent healing effects, but they do cast doubt on the placebo response as traditionally conceived-the so-called power of the sugar pill.

Although much controversy remains, the bulk of the literature supports the proposition that the placebo response is real and potentially powerful, and some of its underlying mechanisms are becoming better understood.

Definitions

Defining “placebo” and “placebo response” in a logically coherent fashion is difficult, perhaps impossible.^5,6 Terms commonly used in medical definitions, such as “inert” and “nonspecific,” range from useless to misleading. Ideally, a definition would be precise enough to clearly demarcate the phenomenon, yet open enough to include a range of possible empirical hypotheses on cause and mechanisms. Terminologic problems, among other factors, have led some thoughtful family physicians to suggest that we eliminate “placebo effect” from our lexicon.^7,8

Assuming that the placebo response falls under the general heading of psychosomatic processes, how wide a range of such processes do we want to admit under the definition? At one extreme, the placebo response can be defined in a very narrow way as bodily changes that occur following the administration of a dummy treatment. This type of placebo response is of little interest to family physicians in daily practice. This definition appeared in a recent review in which the authors claimed that there is no scientific evidence that the placebo response exists.⁹ Since they insisted on the ubiquity and robustness of psychosomatic processes generally, they leave themselves with a conundrum-why should the mind-body connection be so powerful except where it would work by giving dummy medications?

I argue for a broader definition: The placebo response is a change in the patient’s health or bodily state that is attributable to the symbolic impact of medical treatment or the treatment setting. By this definition, a placebo response would be predicted whenever a conscious patient engages in any form of medical encounter (or self-treatment activity). But the definition explicitly excludes from consideration mind-body changes that are not directly related to medical treatment. This definition highlights why family physicians should be particularly interested in the placebo response. Also, since bodily change can be negative as well as positive (nocebo effects),¹⁰ it warns us that if we fail to understand the placebo response, we may unwittingly do harm. For example, a frequently quoted study¹¹ showed that expressing diagnostic uncertainty regarding common nonspecific symptoms can adversely affect symptom resolution.

Frequency of Placebo Responses

The first modern review of the placebo effect made the often-repeated claim that an average of approximately one third subjects will respond to placebos.¹² It was later shown that this average, even if accurate, masks an extremely wide variation in placebo response rates among studies.¹³ Roberts and colleagues¹⁴ recently reviewed the original uncontrolled trials of therapies introduced with great fanfare in past years and now universally dismissed as medically useless. They found a 70% average rate of “excellent” and “good” responses to those treatments before properly designed double-blind trials were conducted. They concluded that in settings of heightened expectancy, the placebo response rate could be much higher than previously thought.