Book Review

The Placebo Effect: An interdisciplinary exploration

N Engl J Med 1997; 337:1855-1856December 18, 1997

Article

The Placebo Effect: An interdisciplinary exploration
Edited by Anne Harrington. 260 pp. Cambridge, Mass., Harvard University Press, 1997. $39.95. ISBN: 0-674-66984-3

This book is based on a conference at Harvard University in December 1994, sponsored by the Harvard Mind, Brain, Behavior Interfaculty Initiative. It brought under one roof some of the leading authorities on placebo and placebo effects, giving many of the chapters the unique quality of coming straight from “the horse's mouth.”

The placebo has become a familiar concept among biomedical researchers and practitioners since it became a prerequisite in randomized, controlled trials in the middle of this century. Yet the state of knowledge about the placebo effect in phenomenological terms (does it exist? to what extent? under what conditions?) and as a neurobiologic construct (which neuronal systems carry it, and which systems modulate behavioral cues and incorporate them into the placebo effect?) is still inadequate. This book makes it clear that placebos contributed critically to the development of evidence-based therapeutics, but research on placebos and placebo effects rarely follows evidence-based principles. For example, any effect measured in the placebo group of a study is commonly defined as a placebo effect. However, without an untreated group (i.e., a group that does not receive either active drug or placebo), it is impossible to quantify the placebo effect, because variation in symptoms or improved compliance with recommended health-promoting behavior may bring about improvement that has nothing to do with receiving a placebo. Yet few controlled studies include an untreated group. Moreover, the search for neurobiologic models to explain how psychological stimuli interact with the brain has advanced considerably in animals, yet the huge gap between animal and human “mind” makes any extrapolation to placebo effects in clinical work difficult.

The book starts with an excellent critical overview by the late Arthur K. Shapiro (with Elaine Shapiro), which drives home the message that the entire pharmacopeia of ancient remedies was based on more than 16,000 placebos. Today's therapies need to prove their superiority over placebo, yet when it comes to psychotherapy, “although many studies report psychotherapy as more effective than placebo, placebo controls are usually inadequate.”

Howard Spiro reflects on the clinical implications of the placebo phenomenon. In summarizing the various psychological forces that bring about a placebo effect, he notes that “compliance is, after all, what our parents taught: good boys and girls who do what they are told will be taken care of.” Robert A. Hahn dedicates his chapter to the scope and foundations of the nocebo phenomenon — “the causation of sickness . . . by expectations of sickness,” an important concept in understanding the scope, mechanisms, and perhaps the neurobiology of placebo. Howard Brody discusses “the doctor as therapeutic agent,” with special focus on the “meaning model” (“A positive placebo response is most likely to occur in a patient when the meaning attached to that illness experience by the patient is altered in a positive direction”). Howard L. Fields and Donald D. Price provide current evidence regarding the neurobiology of placebo analgesia, and although these data have been presented previously, their synthesis is a pleasure to read: “Because few studies of the placebo analgesic effect have included an untreated comparison group, we have very little knowledge of the effect's magnitude, time course, or frequency of occurrence.”

Other chapters include discussions of the role of desire and expectation in placebo analgesics, by Price and Fields, and the role of conditioning in pharmacotherapy, by Robert Ader, whose classic work on conditioning rats to the immunosuppressive and adverse effects of cyclophosphamide by placebo is undoubtedly one of two major breakthroughs in placebo research (the other being the discovery by Levine et al. of the involvement of endorphins in the placebo effect).

Irvin Kirsch eloquently discusses psychological mechanisms of placebo effects, although according to my estimation, by this late stage of the book 80 percent of this message has been delivered by other authors. David B. Morris focuses on a cultural aspect of the topic by delineating “the culture of pain,” discussed in his 1991 book (The Culture of Pain. Berkeley: University of California Press). For the present entry, he traces the placebo effect among Apache healers.

This book highlights and aims at interdisciplinary dialogue, and I found the last chapter, “Placebo: Conversations at the Disciplinary Borders,” most interesting because it allowed the participants to open up. This chapter helped me define more clearly the “cutting edge.” My one disappointment was that the dialogue did not define the near and far vision of neurobiology research and dealt mostly with psychological and philosophical aspects of placebos. Because true advances in placebo research will have to await better insights into the neurobiology of the mind, I had hoped to find more about this aspect.

In general, this book suffers from the weakness of many symposia, in that many data are quoted numerous times by different authors to make the same point. All too often authors detail work done by other authors that is discussed in detail in other chapters. Also, the general lack of participation by neurobiologists gives the impression that the participants are looking for the key where the lamp stands, and not necessarily where the key is likely to be located.

Despite these shortcomings, the book will make fascinating reading for clinicians, neurobiologists, and students, as well as for philosophers and ethicists. More specifically, the book should be considered by those involved in all aspects of clinical pharmacology and therapeutics.

Gideon Koren, M.D.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada