More humanism and less science, that’s what medicine needs.
But humanism is hard work, and so much of science
is just Tinkertoy. Robertson Davies

Why Nothing Works
An Introduction to the Placebo
New York Times, November 11, 2018

I have been interested in the placebo response for many years. This recent NY Times article is a good introduction to the topic. Here are some excerpts and random thoughts:

The author, Gary Greenberg, attended the Society for Interdisciplinary Placebo Studies in Leiden, Holland (2017). He met some key researchers in placebo there.

There is a conviction among many that the placebo is a powerful medical treatment that is ignored by doctors at their patients’ expense. It is especially important for patients with chronic stress-related conditions, such as depression, back pain, chemotherapy-related malaise, migraine, posttraumatic stress disorder, irritable bowel syndrome and other functional disorders. I think that many people with medically unexplained symptoms¹ are in the group that can benefit from placebo therapy.

Ted Kaptchuk is the head of Harvard’s Program in Placebo Studies and the Therapeutic Encounter, housed at the Beth Israel Deaconess Medical Center in Boston. He is featured in this article. His pet theory holds that the placebo effect is a result of complex conscious and unconscious processes embedded in the practitioner-patient relationship, and without them, placebo researchers are hard pressed to gain purchase on mainstream medicine. [This is very similar to some of the work of Michael Balint in the 1950s and 60s, although the didn’t specifically address it as the placebo effect but he called it the application of the “drug-doctor”²

At a 1955 meeting of the American Medical Association, the Harvard surgeon, Henry Beecher, pointed out to colleagues that, in general, more than 1/3 of patients would get better when given a treatment that was pharmacologically inert.³ Researchers needed to assume that the placebo effect was part of every drug effect and it came to be accepted that drugs could be said to work only to the extent that they were more efficacious than placebos.

The drug industry (PhRMA) knows that there is no money to be made in sugar pills and thus, they have no interest in placebos from a research standpoint. Kaptchuk sometimes worries that the rituals embedded in the doctor-patient encounter, that are fundamental to the placebo effect in the body, are an aspect of medicine that has disappeared as researchers and doctors pursue what may be called “scientific” medicine. He feels that medical care is a moral act in which the suffering person puts his or her faith in the hands of a trusted healer. “Science may not be the only way to understand illness and healing, but it is the established way.”

Kathryn Hall, a biochemist, has joined Kaptchuk and they have been studying an enzyme called COMT that modifies people’s responses to pain and pain killers and may be able to shed some light the placebo effect.⁴ One of their hypotheses is that the placebo effect is a biological response to the act of caring: that somehow the encounter itself calls forth healing and that the more intense and focused it is, the more healing it can evoke (think of Balint’s, ‘the drug-doctor). They suggest that the ritual itself is part of what makes the procedure effective, as if the combined experiences of the healer and the patient, reinforced by the special but familiar surroundings, evokes a healing response that operates independently of the treatment specifics (set and setting). If the mind can be persuaded, the body sometimes acts accordingly. Further studies may clarify the nexus between ritual and healing. [As the computer enters the exam room and as patient care becomes a team sport, not simply a patient-doctor dyad, the placebo effect may be diminished.]

An interesting phenomenon has been noticed. Between 1990 and 2013, in some cases, the efficacy of placebos has grown, sharply narrowing the gap with the drugs’ effect from 27% on the average to just 9%. As a result of this, research on pain killers has been difficult to perform since the difference between the drug and placebo effect is so small. This is true mostly in America and it’s not clear why, however it may be because direct to consumer advertising is so common in this country.⁵ What patients see in the media may serve to enhance the placebo effect. [On the back cover of the Sunday Magazine, in which this article appeared is an ad for Mt. Sinai Hospital that may well serve to augment the placebo effect in patients who choose that institution. Here, the placebo effect appears to be serving the mercantile aims of an aggressively marketed medical business.]

A theory that Kaptchuk and Hall favor is that the brain translates the act of caring into physical healing, turning on biological processes that relieve pain, reduce inflammation and promote health, especially in chronic and stress-related illnesses such as irritable bowel syndrome and some heart diseases. Presently, upwards of 30% of the disorders patients present with to allopathic physicians are medically unexplained, and this subset of patients may be good candidates for a generous dose of placebo medicine.¹

Kaptchuk is uneasy about some of the scientific discoveries regarding the molecular basis of the placebo effect. He believes that “the placebo effect can’t be totally reduced to molecules and that it is risky to move the game to a narrow scientific turf. He doesn’t feel it can all be turned into science. Healing is more than just the application of mechanical tools to an ill person. Healing, he believes, is a moral act in which caring in the context of hope qualitatively changes clinical outcomes. The relationship kindled by the encounter between a suffering person and the healer is central and almost entirely overlooked in present day medical treatment.

Mt. Sinai Advert in NYT Sunday Magazine, 11.11.18

References:

1. Medically unexplained symptoms: the person, the symptoms and the dialogue. Houwen J, et. al. Fam Pract. 2017 Apr 1;34(2):245-251.
2. A portrait of Michael Balint: the development of his ideas on the use of the drug “doctor”. Balint E. Int J Psychiatry Med. 1974 5(3):211-22.
3. The powerful placebo. Beecher HK. J Am Med Assoc. 1955 Dec 24;159(17):1602-6
4. Genetics and the placebo effect: the placebome. Hall KT, Loscalzo J, Kaptchuk TJ. Trends Mol Med. 2015 May;21(5):285-94 Free Full Text.
   Abstract: Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, ‘the placebome’, is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care.

5. What are the public health effects of direct-to-consumer drug advertising? Almasi EA1, Stafford RS, Kravitz RL, Mansfield PR. PLoS Med. 2006 Mar;3(3):e145. Free Full Text.

Addendum:  For more on Placebos and Ted Kaptchuk see Michael Spector’s “The Power of Nothing” in the New New Yorker, December, 2011.

Also Ted Kaptchuk’s talk about placebos, TEDMED 2011.