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Medicine is simultaneously both easy and hard. As an Infectious Disease doctor, my day can be summed up with the phrase “me find bug, me kill bug, me go home.” Sometimes it is just that simple. A lot of the time it isn’t. I may not be certain what the infection is, or even if the patient has an infection, or allergies and/or antibiotic resistance limit therapeutic options, the host has co-morbidities that limit effectiveness, and the patient has no financial resources for the needed treatment.

I am lucky, since most infections are acute, make people feel terrible, and require a relatively short course of therapy during which the patient feels better. I rarely have to worry about compliance with the treatment plan; it is the rare patient, usually a heroin user or a particularly irascible old man, who will not follow through with their antibiotic course. I do not have to worry about chronic or symptomless diseases like diabetes or hypertension or the complications of obesity where long term compliance often limit therapeutic success. Long term it is difficult for many people to stick with their therapeutic plan, much less their diet and exercise resolutions.

Infectious diseases is a job where I do not have to concern myself about placebo effects. As readers of the blog are well aware, I do not think there is any such thing as a placebo effect that has any clinically meaningful application, especially in the world of infectious diseases. Infections are usually a binary proposition: either you are infected or you are not and either I am curing you or I am not.

Still, there is more to medicine than me find bug, me kill bug, me go home. Often most of the time on a consult is spent talking with the patient: explaining what they have, why they have it, what we are going to do about it and what they can expect.

As an aside, while I ‘take a history’, as we say in the parlance of the field, patients provide a story, a narrative. Much of what the patient has to say is frequently of little importance to the medical matter at hand, and there is something about illness that lends people to philosophizing. At length. Especially at 4 o’clock in the afternoon on Friday. I hate to tell you this, but the details of your life and the philosophy of your existence are neither that interesting nor that original. You, like me, are really not that compelling.  I have heard the content and what you are saying before, more times than I can count.

At one of the hospitals I go to they report metrics on patient satisfaction, and one is “My Doctor listens carefully to what I said.” We are usually around 80%, but I point out that at least 20% of the time the patient is not saying anything worth listening to. The elderly male I saw last Friday at the end of the day felt obligated to go on about his grade and  high school GPA, I guess to let me know how smart he was. Such irrelevant soliloquies, at least irrelevant to making a diagnosis although they do add insight into the patient, are common. I pretended to listen with interest, looking for the right moment to interrupt, glad we are not telepathic.  I am often glad we are not a telepathic species.

I suspect part of the allure of alternative medicine providers is that the dull details of my life, which are of no interest to anyone but me and (maybe) my family, are of endless interest to the fake diagnosis and treatment by the homeopath or naturopath. The patient gives us a story, we extract the small amounts of information that are relevant to the diagnosis, but do not give a narrative back in return. We give data and odds and studies. Alt med providers return a narrative and a story, incorporating the faux uniqueness of their patient. The problem with medicine, and the source of its diagnostic and therapeutic power, is that there is usually nothing whatsoever special about you, or me. Humans operate under very tight and predictable operational parameters: physiologically, emotionally, and psychologically.  Human variations are usually trivial, since extreme variations are fatal. People prefer to operate under the delusion they are interesting and unique and SCAM practitioners feed into that.

I recognize that conversations with the patients are important for a variety of reasons, since the more they understand about their infection and its treatment, the better they will be able to adhere with their compliance. Or comply with their adherence. Whatever the current buzz word is for getting the patient to do what you want them to. While I think the patients attitude has nothing to do with whether I will successfully kill the MRSA on their aortic valve, being ill is difficult, and the better they cope and comply, the better will be the quality of their life during the illness.

We have four possibilities when treating an illness:

  • We can improve the pathophysiology and the patient feel better. That’s the best case scenario. It is what I strive to accomplish with my patients.
  • We can improve the pathophysiology , but the patient feels no better or feels worse. My fathers chemo for his non-Hodgkin’s lymphoma cured the tumor, but he never quite felt well after.
  • We can not improve the pathophysiology, but the patient feels better. In my world, that is mostly when patients are on hospice, but it applies to chronic pain.
  • We can fail to improve the pathophysiology and the patient feels worse. That is the worst case scenario.

I have long realized the importance of what we referred to as a resident as the supratentorial component of illness. It is a large part of being a doctor, but one of the more difficult parts since the approach differs with each patient.   I do not need to individualize the antibiotics for your MRSA osteomyelitis, but I do for how I communicate about your illness.  Is the patient smart?  Stupid?  Uneducated?  Overeducated?  Confused? Drugged? Depressed? Demented? Fatalistic?  Unrealistic?  The message needs to fit the recipient.

At the heart of the communication with patients is honesty and truthiness. I have to get a sense of who you are and then tell you what is occurring. The patient-physician relationship is based on honesty, and without honesty there can be no autonomy, the first of the on the principles of medical ethics:

Autonomy. The principle of autonomy recognizes the rights of individuals to self-determination. This is rooted in society’s respect for individuals’ ability to make informed decisions about personal matters.

Beneficence and Non-Maleficence, the other key principles, are always two and three on the list, perhaps it is always alphabetical.  A patient cannot make informed decisions if they are not told the truth.

As a rule, autonomy trumps beneficence and non-maleficence. I can’t lie to you, even if it is to your benefit. No weasel words or Romneyesque evasions, but of course there are many ways to tell the truth: do I say an 80% cure rate or a 20% failure rate? Emphasize the good? Dwell on the bad? It is not what you say, but how you tell the truth that can be important, but you always have to be aware of the line and not cross it. I wonder how well other docs do, as I not infrequently get a comment from a patient that they appreciated how clear I was in my explanation of the medical situation, good, bad and indifferent. That I told it like it is.

We all can manipulate our patients in subtle ways.  A classic example is sitting down when you go into a patients room. Patients will rate the time spent as longer if the doctor sits down instead of stands, even if the actual time is no different. There are other tricks (I am not certain I like that word) that can be used to enhance the therapeutic interaction. I don’t think of it as lying, but is part of being a good doctor, especially in an era when patients can be referred to (never, ever by me) as clients and consumers and it is our job to have happy customers.

Even if I thought the placebo effect existed in any meaningful way, I could never use it since at its heart it violates the prime directive of medical ethics. It is why editorials in JAMA, like Lessons From Recent Research About the Placebo Effect—From Art to Science  by Howard Brody MD, PhD and Franklin G. Miller PhD , besides only presenting half the information, give me the willies.

Dr Brody is the author of The Placebo Response: How You Can Release the Body’s Inner Pharmacy for Better Health, which I have not read, but the Amazon summary says

According to Brody, the placebo phenomenon–which he pronounces mysterious and unknowable at its very heart–is when the convergence of healing signals, assigned meaning, and human expectations stimulates the body’s inner healing power. The patient’s positive mental and emotional reaction to a medical intervention releases what Brody terms the “inner pharmacy.” In other words, even though the treatment is benign, the body’s biochemical pathways are stimulated to induce healing in the same manner actual medicines do. “Could harboring hope, faith, or expectation be genuinely potent factors in the healing process?” Brody asks, “I believe they are. In fact, I see them as the heart and soul of the placebo response.

Doesn’t look like a promising start. But what is placebo?

In popular understanding, placeb is giving a sugar pill instead of a real medicine, like Doc Martin did in the episode I saw yesterday. The teenage girl wanted a larger chest and he gave her some peppermint breath mints to take once a month for a year and he pointedly never contradicted her misunderstanding as to what she was receiving.  Of course the young lady instantly went from poor self esteem  who was easily bullied by the other girls to aggressive young lady who verbally slapped down her bullies with new found self confidence. Of course, in keeping with the true placebo effect, no anatomy was changed.  I have only seen a few Doc Martin episodes to date, but so far I have been impressed with accuracy of the medicine.

Placebo is also used in clinical trials, an inert treatment that is the surrogate for all the other confounding factors in patient treatments that can determine results: natural history of disease, physician and patient bias, regression to the mean, etc. Interactions with health care providers can have effects on patients, especially for subjective symptoms. As studies and their meta-analysis have consistently demonstrated, placebo in clinical medicine does not alter the underlying pathophysiology, the objective endpoints, only the subjective endpoints. Placebos do not treat the underlying disease, they only alter the symptoms, and not by much. Symptom relief is not a bad thing, as long is it does not violate autonomy, beneficence non-maleficence. Kind of hard to do when the placebo effect is based on lying to the patient.

The JAMA editorial completely ignores the first use of placebo, and ignores the data that placebo has no effect to alter pathophysiology. I suppose it is how you read the literature. Referring to Placebos without deception: a randomized controlled trial in irritable bowel syndrome (blogged about by Dr. Gorski when it came out)  that they interpret as

Recent research now challenges the prior beliefs that placebo treatments must be prescribed deceptively in order to work.

Patients were told in the study that

…placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes (bold mine).

The study included four talking points:

“…1) the placebo effect is powerful, 2) the body can automatically respond to taking placebo pills like Pavlov’s dogs who salivated when they heard a bell, 3) a positive attitude helps but is not necessary, and 4) taking the pills faithfully is critical. ”

That, to my mind, is deceptive, and while I am not surprised that patients reported feeling better, as they often do after a visit with the doctor, it was based on several lies, and the study would violate patient autonomy if applied outside of a clinical study. You tell a patient up front that a positive attitude helps, and you are not surprised when they report doing better.  Being in a medical trial will lead to the patient trying to please the researcher, a clinical trial Stockholm syndrome.

I’ll grant you that there are “Two intertwined psychological mechanisms are thought to underlie placebo effects—expectancy and conditioning” and that patients can be manipulated in clinical trials to report feeling better. Placebo effects are neither clinically impressive in their effect nor an ethical for a practicing clinician, but ones man’s ethics is another man belly laugh.  Note, the authors start out saying the effects are psychological, and changing psychology will not make your breast cancer remit.

But then, something changes. One moment I see a Victorian woman looking in a mirror, then suddenly I see a skull. Because placebo becomes more than a sugar pill, more than the placeholder for the numerous confounding variables and biases that muddy the waters of a clinical trials.  The placebo effect are pleural and are as many as sands in the hour glass.

Neurophysiology and neurochemistry suggest that there are multiple placebo effects, with different neurobiological mechanisms, depending on the organ system and the target illness.

Good. It there are as many placebo effects as there are illness, perhaps I can use it. Failure rates with vancomycin for MRSA hover around 30%. Maybe I can use placebo effects to help, but it never seems to be the case. Infections are recalcitrant to placebo effects. Instead they mention the usual suspects of subjective experience: pain and irritable bowel syndrome. But it turns out that I have been practicing placebo medicine all this time after all. You can elicit the placebo effect by being, well, a good doctor.

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.

Everything you do as a clinician evidently can elicit the placebo effect. Even “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.” is a placebo effect. Every interaction becomes the opportunity to elicit a placebo response and I suppose, failing in these characteristics will enhance the nocebo effect.

It is a definition of placebo so broad as to be useless. What isn’t an opportunity to elicit a placebo or nocebo effect? When a definition apparently encompasses everything, it becomes nothing.

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.

Show of hands; how many out there like to prescribe to “unnecessary and potentially harmful drugs”?  And the sentence suggests the authors knows that maximizing the powers of the mind is not well supported by scientific evidence.

The patient-physician interaction can be complex and multifaceted. All human interactions can be complex and multifaceted. As health care providers we are trying to influence the patients behavior and attitude in an attempt to heal the patient. In the old days it was called a good bed side manner; as I have said before no different, but more complex, than the salubrious effect one ape has on another when they are groomed. A good bedside manner helps the patient feel better but doesn’t make their brain tumor or liver abscess shrink.

Having a good bedside manner and helping the patient feel better about the psychological/subjective components of their illness has always been part of medicine, although obviously some are better at it than others, and some are more interested than others.  You don’t become a pathologist because you like to work with people.  A good bedside manner has always helped the patient feel better, there is no mystical underpinnings to the process.   It is not “the practitioner has many means to help each person activate the potentially powerful inner pathways that assist healing.”

There’s the leap that drives me nuts: placebo is good for symptom relief, nothing more. Nothing is healed, although I have an old school idea of healing: the process is cured. A healed wound is closed and has a scar, not having less pain. Placebo heals nothing, There are no potentially powerful inner pathways by which placebo heals. At best, when lied to, you will feel better.

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.

As it should be. If trials show an intervention does nothing, it should not be used. Substitute ‘pharmaceutical medication’ for ‘acupuncture’. Would you still recommend it?

An open question for future research and ethical reflection is whether such modalities can be recommended consistent with informed consent.

Informed consent: Acupuncture does nothing. There are no meridians, there is no chi, and studies are clear acupuncture does nothing to alter your underlying disease. At best you may think your pain is decreased, but the effect is not sustained. Besides having no efficacy, there are the occasional severe and even fatal complications from the procedure and many practitioners are not particularly fastidious with the techniques of infection prevention. It will cost you $100.

Doesn’t take much ethical reflection for me.

Of course virtually all of SCAM, from acupuncture on down the alphabet, does nothing to alter underlying anatomy or physiology. No healing is accomplished.  And all SCAM results is placebo: the psychological effect of a lie believed to be beneficial.  A good therapeutic relationship with a SCAM provider that is based on a lie is not, in my narrow world, ethical. I am not a means justifies the ends kind of guy.

They go from the well defined effect of placebos for modifying symptoms in clinical trials to every interaction being able to cause placebo effect to placebos can heal. I tend to like clear thought, and these essays are written in no small part to help me clarify my own thoughts on the topics about which I write. When everything is placebo, and somehow the mild decrease in IBS symptoms is translated into a powerful mind-body medicine beyond mild symptom relief, I look in vain for clear thinking. And how understanding how a mild decrease in symptoms heralds a “bridging the long-standing gap between the scientific and humanistic orientations of modern medicine,” I can’t see.  I also don’t see the gap in my practice.  The gap is not in medicine, but in the variation in providers, not all of whom are proficient or interested in maximizing the doctor-patient relationship.

Give half the data and wildly extrapolate. That is not from Art to Science. That is from molehill to mountain.

Addendum.  As I finish this essay, eradicating all the typos and grammatical mistakes for Dr. Gorski’s sake, an interesting study crossed my desk:  Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST),  which concluded

Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery.

It takes a while for me to read and digest an new article, my initial take is that being adherent in one sphere of your care probably means you are adherent on other spheres of your care.  Being adherent in general leads to to better outcomes, and there are a multiplicity of factors that decrease adherence and worsen outcomes.  It is never one intervention that leads to good, or bad, outcomes, but the summation of many small interventions.  Adherence to placebo is probably  such a marker.  I saw no reason to invoke  powerful mind-body effects at work.

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  • Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, from 1990 to 2023. He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly,  the ‘Attending Most Likely To Tell It Like It Is’ by the medical residents at his hospital. His multi-media empire can be found at edgydoc.com.

Posted by Mark Crislip

Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, from 1990 to 2023. He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly,  the ‘Attending Most Likely To Tell It Like It Is’ by the medical residents at his hospital. His multi-media empire can be found at edgydoc.com.