‘Should doctors prescribe placebos?‘
Recent research suggests symptom benefit in certain conditions/diseases from open-label placebos, i.e., when patients know they are getting placebos. This is a sea change from traditional understanding of placebos as ‘inert’ or ‘ineffective’ ‘sugar’ pills given by doctors to mollify demanding patients, a change whose long-term implications for the practice of medicine are profound, though still unclear.
Placebos: From Wilful Deception (Medieval Times) to Potentially Helpful Adjuncts (Current Era Placebo Research)
Reviews state medical dictionaries began including the word Placebo in the late 18th and early 19th centuries as (see below from 1),
an epithet given to any medicine adapted more to please than to benefit the patient.
However, in recent years, research exploring how placebo can help alleviate certain symptoms of certain diseases changes age-old understanding of this medical mainstay. Such research reveals the extent to which complex mind-body interactions strongly influence physiology so much so that the noted placebo researcher, Fabrizio Benedetti suggests (2):
words and drugs may use the very same mechanisms and the very same biochemical pathways.
Clearly, placebos tap into cognitive, even emotional and sensory, pathways whose power science-based medicine has hitherto tended to under-appreciate. Benedetti showed this in a rather dramatic fashion by giving opioid pain medication to patients either openly or hidden, with clear evidence of increased benefit among those who knew they got the pain medication compared to those who didn’t know (3). In the twenty years since, Benedetti has shown similar therapeutic benefits in other conditions such as anxiety and Parkinson’s.
Note that in such open-hidden studies as Benedetti pioneered, all the patients got the same medication, even the same dose of medication. The ‘placebo‘ in these studies was merely the act of revealing to the patient that they were getting a medication, i.e., engaging their expectations. Such studies uncovered how perception of care itself carries a therapeutic element.
Parsed in this manner, we could thus split traditional placebos into two groups, placebos that entail deceit versus those that don’t, the so-called open-label placebos.
While the effect of giving placebos openly was studied as far back as 1963 (4), systematic efforts to study how placebos work their effects are of much more recent vintage. Pioneered by prominent placebo researcher, Ted Kaptchuk, a handful of studies on open-label placebos reveal a symptom benefit in conditions with substantial psychosomatic component, conditions such as pain (5), itch (6), asthma symptoms (7), pain experienced in GI tract-related problems such as Irritable bowel syndrome (IBS) (8).
One of the biggest caveats of open-placebo studies, however, is one least discussed, namely, the extent to which a Clever Hans effect is in play. Specifically, how to ensure that placebo-taking participants aren’t fudging their symptom improvement in order to appease the caregivers conducting these trials? Such a consideration is all the more relevant given the fact that in the asthma study, participants knowingly taking placebo inhaler reported similar symptom improvement yet objectively assessed lung function improved only in those who got albuterol (7). Did the asthma patients who knowingly got placebo inhaler really feel better even though they still couldn’t breathe better? Clearly, some placebo effects would be on stronger grounds if they withstood scrutiny by objective tests.
Nevertheless, research into placebos expands the definition of placebos from mere things, inert or ineffective pills, to processes such as the treatment ritual, the patient’s expectations and the quality of the doctor-patient communication, all part of behavioral conditioning (see below from 9).
Do placebos have the potential to revolutionize medicine by reliably delivering tangible benefits to patients by capitalizing on such intangibles? That’s the proverbial x$ question. These are still early days in placebo research. We are far from understanding the molecular mechanisms at play. Indeed, Benedetti believes different placebos use different mechanisms (10).
However, if such effects could be harnessed reproducibly, it could transform the very practice of medicine. For instance, we could allay drug toxicity by reducing dose or frequency and yet gain similar benefit. Not only would this benefit patient health, it would also reduce economic cost. Sham surgeries with their inherently lower collateral biological costs could accelerate healing, not to mention, again, reduce economic costs. Whether such effects are capable of being exploited in a predictable manner remains to be seen.
‘But is it ethical for doctors to prescribe them [placebos]?‘
Prescribing placebos is ethically inherently problematic since it involves deceiving patients. We are reminded of this nowhere more so than in very meaning of the word, Placebo, Latin for ‘I will please’, which in Medieval English appears to have been used as a synonym for sycophant. Consider the sycophantic nature of the character Placebo in The Merchant’s Tale by Geoffrey Chaucer (11).
In the US, the American Medical Association has published unambiguous guidelines that clearly indicate when and how physicians can and should prescribe placebos (see below from 12, emphasis mine).
Physicians may use placebos for diagnosis or treatment only if the patient is informed of and agrees to its use. A placebo may still be effective if the patient knows it will be used but cannot identify it and does not know the precise timing of its use. A physician should enlist the patient’s cooperation by explaining that a better understanding of the medical condition could be achieved by evaluating the effects of different medications, including the placebo. The physician need neither identify the placebo nor seek specific consent before its administration. In this way, the physician respects the patient’s autonomy and fosters a trusting relationship, while the patient still may benefit from the placebo effect.
A placebo must not be given merely to mollify a difficult patient, because doing so serves the convenience of the physician more than it promotes the patient’s welfare. Physicians can avoid using a placebo, yet produce a placebo-like effect through the skillful use of reassurance and encouragement. In this way, the physician builds respect and trust, promotes the patient physician relationship, and improves health outcomes.
Based on these guidelines, Charlotte Blease, Luana Colloca and Ted Kaptchuk argue (see below from 13),
open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically.
1. De Craen, Anton JM, et al. “Placebos and placebo effects in medicine: historical overview.” Journal of the Royal Society of Medicine 92.10 (1999): 511-515.
2. Benedetti, Fabrizio. “The placebo response: science versus ethics and the vulnerability of the patient.” World Psychiatry 11.2 (2012): 70-72. http://onlinelibrary.wiley.com/d…
3. Colloca, Luana, et al. “Overt versus covert treatment for pain, anxiety, and Parkinson’s disease.” The Lancet Neurology 3.11 (2004): 679-684. https://s3.amazonaws.com/academi…
4. Park, Lee C., and Lino Covi. “Nonblind placebo trial: an exploration of neurotic patients’ responses to placebo when its inert content is disclosed.” Archives of General Psychiatry 12.4 (1965): 336-345.
5. Carvalho, Cláudia, et al. “Open-label placebo treatment in chronic low back pain: a randomized controlled trial.” Pain 157.12 (2016): 2766. https://pdfs.semanticscholar.org…
6. Meeuwis, Stefanie H., et al. “Placebo Effects of Open-label Verbal Suggestions on Itch.” https://www.medicaljournals.se/a…
7. Wechsler, Michael E., et al. “Active albuterol or placebo, sham acupuncture, or no intervention in asthma.” New England Journal of Medicine 365.2 (2011): 119-126. http://www.nejm.org/doi/pdf/10.1…
8. Kaptchuk, Ted J., et al. “Placebos without deception: a randomized controlled trial in irritable bowel syndrome.” PloS one 5.12 (2010): e15591. http://journals.plos.org/plosone…
9. Schedlowski, Manfred, et al. “Neuro-bio-behavioral mechanisms of placebo and nocebo responses: implications for clinical trials and clinical practice.” Pharmacological reviews 67.3 (2015): 697-730. https://pdfs.semanticscholar.org…
10. Benedetti, Fabrizio. “Placebo effects: from the neurobiological paradigm to translational implications.” Neuron 84.3 (2014): 623-637. https://pdfs.semanticscholar.org…
11. Elliott, David B. “The placebo effect: is it unethical to use it or unethical not to?.” Ophthalmic and Physiological Optics 36.5 (2016): 513-518. http://onlinelibrary.wiley.com/d…
12. Bostick, Nathan A., et al. “Placebo use in clinical practice: report of the American Medical Association Council on Ethical and Judicial Affairs.” Journal of Clinical Ethics 19.1 (2008): 58. http://academicdepartments.musc….
13. Blease, Charlotte, Luana Colloca, and Ted J. Kaptchuk. “Are open‐Label Placebos Ethical? Informed Consent and Ethical Equivocations.” Bioethics 30.6 (2016): 407-414. https://www.ncbi.nlm.nih.gov/pmc…