Lessons From Recent Research About the Placebo Effect—From Art to Science

Medicine has been of 2 minds, so to speak, regarding the placebo effect in clinical practice. On the one hand, the placebo is disparaged as an inert and deceptive intervention intended to please or placate the patient but without any potential to produce meaningful therapeutic benefit. On the other hand, placebo effects are touted as having the power to produce substantial symptomatic relief across a wide range of medical conditions. Until recently, scientific data that elucidate the mechanisms of placebo effects and evaluate their potential to significantly enhance patient care have been lacking. During the past decade, there have been advances in scientific research on the placebo effect, paving the way for evidence-based techniques for promoting placebo responses in clinical practice in ethically appropriate ways.¹ Additionally, practitioner surveys indicate that physicians today appear much more comfortable acknowledging the placebo effect as a therapeutic tool consistent with a scientific understanding of the mind-body connection.^{2 - 3}

Recent research on the placebo effect has been conducted with more methodological rigor than older studies, allowing better discrimination between true placebo responses and confounding variables such as natural variations in symptom severity. For instance, neuroimaging studies have demonstrated some of the pathways activated when study participants receive placebos and then experience therapeutic responses, including release of endogenous opioids and dopamine. Neurophysiology and neurochemistry suggest that there are multiple placebo effects, with different neurobiological mechanisms, depending on the organ system and the target illness.¹

Moreover, experimental comparisons of open administration vs hidden administration of analgesic and antianxiety medication (ie, with hidden administration involving the same dose of medication administered by an infusion pump concealed behind a screen) consistently showed a greater effect when patients knew they were receiving the drug compared with the same dosage given by hidden intravenous infusion.⁴ This suggests that a substantial proportion of symptomatic relief from these drugs was derived from the positive effects of the clinical encounter, which augments their inherent pharmacological properties.

In addition, in a study of patients with irritable bowel syndrome, sham acupuncture treatment administered impersonally resulted in a greater therapeutic response than no treatment, but the addition of a warm interpersonal relationship independently added a substantial therapeutic benefit.⁵

Two intertwined psychological mechanisms are thought to underlie placebo effects—expectancy and conditioning.¹ Positive beliefs about future outcomes, especially when connected with an intervention recommended by a clinician, may trigger those outcomes. Moreover, much of medical practice consists of repeated rituals that may create conditioned responses that can be reactivated in the future by placing the patient in a similar environment. In conscious persons, conditioning overlaps with learning, thus creating positive expectancies. There remains much to be discovered about taking advantage of placebo effects in clinical practice. However, promoting placebo responses no longer falls within the black box of “the art of medicine” but has become amenable to scientific experimentation in service of evidence-based patient care.⁶

How can the engaged, compassionate practitioner best stimulate placebo effects? The first step is to identify the task as an explicit goal of patient encounters and relationships. Rather than deny medicine's ritual elements as incompatible with or incidental to scientific aspirations, clinicians can capitalize on the common rituals of daily practice. For example, rather than advising the patient to get more exercise, a physician can write a prescription for exercise on a prescription pad, thus using ritual in a way designed to elicit a placebo response along with increased adherence.

Physicians may elicit placebo effects by altering the meaning of the patient's illness experience in a positive direction. Alternatively, by means of conditioning, the physician taps latent meaning that has become associated with past healing events. Good ways to enhance everyday encounters include inviting and listening carefully to the patient's story of illness experience, offering a satisfying explanation for the patient's distress, expressing care and concern, communicating positive expectations for therapeutic benefit, and helping the patient to feel more in control of life in the face of the illness.⁷ None of these activities need add considerable time to the encounter, because each does double duty. Listening well is a part of good history taking. Explaining the illness and proposing positive ways to deal with illness are part of therapy and patient education, besides contributing to shared decision making. Care and concern can be expressed by the clinician's attitude and demeanor as the other activities are performed.

Although practitioners' interest in promoting placebo effects is heartening, some physicians appear willing to prescribe unnecessary and potentially toxic medications, such as antibiotics and sedatives, for their placebo effects.^{2 - 3} Appreciation of mind-body science would reassure physicians that they need not prescribe such placebo treatments to alter the meaning in a way that promotes positive outcomes. But what about low-risk interventions such as acupuncture to treat low back pain? Today, if rigorous clinical trial evidence shows such modalities to be better than no treatment or usual care but no better than placebo, the treatment is often summarily dismissed. An open question for future research and ethical reflection is whether such modalities can be recommended consistent with informed consent.⁸

Recent research now challenges the prior beliefs that placebo treatments must be prescribed deceptively in order to work.⁹ This suggests 2 different approaches. Prescribing sugar pills openly as helpful placebos, taking advantage of the ritual of therapy, may be a superior alternative for some patients than a watch-and-wait strategy. Others, however, would argue that there are many other ways to invoke placebo effects via therapeutic rituals and positive communication and relationships. Relying on pharmacologically inert pills, even with patient consent, is largely unnecessary and may merely reinforce deleterious habits of overmedication.

Although patient beliefs vary depending on geography, culture, and education, at least some of today's patients are eager to become active collaborators in mind-body healing practices. Many patients will be relieved to learn that the physician wishes to avoid unnecessary and potentially harmful drugs and wants to maximize the powers of the mind alongside those drugs and other modalities that are well supported by scientific evidence. By sharing with patients the general sorts of techniques that can alter meaning, physicians can empower patients to become their own placebo stimulators. For example, the clinician may ask a patient: “Tell me about the times when you feel that your asthma is really in charge of your life. Then tell me about the times when you feel that you're running your life despite the asthma. Now, let's talk about ways we can help you to do more of those things that make you feel more in charge.” In short, the practitioner has many means to help each person activate the potentially powerful inner pathways that assist healing. Involving the patient in such a dialogue may help to determine whether this patient would do well with a nonpill ritual for stimulating a placebo effect, or whether the patient is so wedded to medications that only the use of an inert-content pill or similar treatment will suffice.

Developments in research on placebos suggest that the time has come to translate the science of placebo effects and knowledge regarding techniques for promoting placebo responses into clinical practice and medical education. This holds promise for bridging the long-standing gap between the scientific and humanistic orientations of modern medicine, with a potentially important pay off in enhancing patient care.