The Placebo Effect: Physiology or Psychology?

and the doctor’s ethical dilemma

Abstract

To address if in the excitement of entering the golden age of science and technology we have lost our historical greater understanding of psychology, contextual and social manipulations. Although this model has understandably taken a backseat the placebo has a brilliant success rate and this essay aims to evaluate the ethical hurdles – informed consent, the hazards of deception, the extent of a physician’s duty, paternalism and therapeutic privilege- to see if old and new medical approaches can converge to maximise patient welfare.

Introduction

“As beauty lies in the eye of the beholder, so pleasure and gratification lie in the mind of the patient. A placebo is a nonentity – its efficacy depends not on what is given but on what is received”.[1]

Feelings of uncertainty and vulnerability have been the Achilles’ heel of humanity since Achilles himself strolled the earth and in our search for control over our wandering destiny healers, shamans and doctors have always existed in society. However, except for the rare and isolated cases of medicines containing active pharmacological ingredients (such as quinine in cinchoma bark) all remedies dispensed before the last century or so have contained little or no active ingredients. [2]. As recently as 1952 an analysis of 7,000 prescriptions suggested around one-third lay in the placebo range. [3]

Thus in the words of Arthur Shapiro, “the history of medical treatment can be characterized largely as the history of the placebo effect.”[4] In the modern world of pill-pushing nutritionists, evil pharmaceutical corporations and flaky statistics adored by the sensationalist media [5], the fuzzy mechanism and murky waters of the placebo effect are largely ignored. The blame for this should certainly not rest in its entirety at the doors of the humble family physician, for he or she is only responding to the increasing droves of patients brandishing internet printouts or newspaper cuttings of the latest prescriptions favoured by the tabloids. Possibly the concepts of the placebo effect can never be gasped until the structure of medical education itself undergoes considerable reform, “From the outset, the road to a medical career seems congruent with reductionist science but incongruent with social science … (generally favouring] a knowledge of ‘things’ (e.g. the details of prokaryotic cell transcription and translation) over an understanding of ‘relationships’ (e.g. among predators, prey, plants, insects and climate).” [6] If we are to later conclude that the placebo effect involves solely or largely relies upon aspects of psychology, then it is conceivable we may struggle to inaugurate our conclusions for best practice through a profession of reductionist and scientific minds.

Definition

There appears to be much confusion around the definition of a placebo, yet as good scientists, we cannot hope to investigate that which we cannot define. The Oxford Precise Medical Dictionary (which, presented gratis alongside BMA registration to the proverbial bright-eyed and bushy-tailed first years must surely have a defining role in our perceptions and preconceptions) most erroneously commences its definition, “a medicine that is ineffective”, before continuing, “but may help relieve a condition because the patient has faith in its powers.” [7] Although 96% of physicians believe “placebos have therapeutic effects” the same study found that 51% of physicians endorsed the definition of a placebo as “an intervention that is not expected to have an effect through a known physiologic mechanism”. [8) Shapiro felt it was key to differentiate between

Placebo; any action given to have an effect that is non-specific to the condition being treated, and
Placebo effect; which may or may not occur and may be favourable or unfavourable

Benson and McCallie supplement Shapiro’s explanation of the placebo effect commenting it, ‘maybe subjective or have objective physiologic manifestations.” [9] Put simply “It is now evident, albeit strange and counterintuitive, that receiving – rather than the actual content of – medical treatment can initiate a healing process.” [6]

Potential Potency of the Placebo

Let me first attempt to provide a by no means exhaustive list of variables that have been investigated as affecting the might of placebo outcomes. They include; the attitudes of the doctor towards the patient; the hospital ward setting and the attitudes of the staff; the personality condition and interests of the patient; the size, colour, shape, taste and number of tablets or capsules; the doctor’s verbal suggestion regarding the effects of the medicament and the numerous alternative manners of administration including injections and even, most radically, surgery.

Before the exploration of the placebo effect in its own right, it was (and to a devastating extent still is) ignored as a polluting factor in mainline scientific research. WJ. McGuire characterized 3 stages in the life of an artefact – first ignored, then controlled for its contaminating effects and then studied as in its own right, and it is to be much lamented that we appear to be struggling to straddle the bridge to the final stage. [10]Initial research into the placebo effect focused on patient personality, and numerous studies tried to define the ‘placebo responder’ with “a vague undertone of condescension” but this produced little or no results of weight. Subsequently, a phase of reclassifying the placebo as misattribution and reattribution of symptoms came into vogue before research gradually realigned itself into investigating the various routes of administration of placebos and their effects on potency. [10]

Unlike the elusive placebo responder, research into pill colour has been significantly more successful. A study with student teachers found pink and blue pills to have stimulating and tranquillizing effects respectively and produced significant results not only with subjective values such as mood and self-perception of mental processing but also on objective values such as pulse rate, reaction speed and blood pressure. [11] Studies investigating the number of pills have all found a greater number of pills to have a greater effect, the most noted finding in one study being, “the effect of increasing the number of pills parallels that of increasing the dosage level”. [2]

It will come as no surprise to the well scientific reader that staff attitudes towards treatment outcomes have a significant impact on results. This is of course the reason behind the ‘double blind’ necessity in the randomised controlled trial gold standard in current scientific and medical peer-reviewed publications. However, Feldman’s findings in 1956 that, “the greatest patient improvement by far was obtained by those physicians who were most enthusiastic about medication and sure of its value” were if not shocking, certainly newsworthy. [12]

The placebo effect, determined as it is by expectations, also varies cross-culturally. This is illustrated by the effect of expectations more broadly, such as with the experiences of people who drink placebo alcohol. It has been shown that their behaviours are far closer linked to their cultural understanding of what it means to be ‘under the influence’ than they are to the actual pharmacological influence of real alcohol. [13]

Notoriety of the Nocebo

The nocebo effects- or negative placebo effect- is less widely recognized and does not even feature in my aforementioned Oxford Concise Medical Dictionary. It was more commonly branded by the sensationalist media as the ‘voodoo death’ and has also been noted as self-willed death in patients with melanoma [14], and the death of a second member of a long-married pair shortly after the first member dies. [15] Understandably due to ethical constraints (specifically non-malevolence) studies have been limited to those of an observational nature. There is a substantial wealth of material on the nocebo effect to fill an essay alone but I have chosen to focus on the placebo.

Placebos and the principles of ethics

The placebo effect presents a vast conflict between two of the founding principles of the ethical theory – autonomy and beneficence. Traditionally the four pillars of ethical wisdom are treated with equal respect but of course, their personal tanking varies between individuals. One of the problems of applying any set of ethical values in modern Britain is that in such a heterogeneous society we are so culturally diverse, there are no common principles, or at least too few. [16]

Historically, the ethics of deceiving patients for their ultimate gain (in health) have been unproblematic for the great philosophers; Socrates (in Plato’s words) “knew that by treating the whole you had a greater effect. He understood the necessary effects of circumstance, spells and grandeur of amplifying [the placebo].” Plato too was paternalistic, viewing a doctor as, “the person whose expertise entitles him to others obedience.” Thus, the ancient greats would have us sweep aside the issue of autonomy and embrace beneficence as our primary goal.

However, the modern arena is more concerned (through necessity) with where law and ethics overlap. Paternalism speaks of old-fashioned medical practices, of old-boys clubs and other such remnants of a bygone era. Some modern ethical thinkers feel that the “Western world’s use of medicine is in itself dysfunctional- human problems and values become medicalised and compartmentalised within a specific, limited and often inappropriate framework”. They argue that over deference to medicine by individuals, coupled with a legal establishment reluctant to challenge medical decision-making are leading us away from autonomy and that this is a danger. [17]

Possibly it would help our discussion to clarify exactly what duties a doctor does and does not have to their patients. Are any of the duties of health professionals strongly binding in all circumstances? Those who argue utilitarianism benevolence (greatest net aggregate of happiness) would take organ donation to extremes that few reasonable medical professionals would be comfortable with – in short, the problem with utilitarianism does not allow for any unconscionable acts. It suggests that a doctor once qualified and fully able, should justify and execute every decision in his or her patient’s best interests, including whether to lie in on weekends, make it home for dinner with his or her family and whether to read a novel in the evenings or peruse the latest journal papers released online. Thus we accept benevolence to a point, perhaps to the position at which it endangers the best interests of others, including ourselves, but we do not accept it as dogma to be unilaterally applied without further consideration.

Let us now consider autonomy itself in more detail, whilst often considered a fad of recent times, its lack of mention in the Hippocratic writings does not automatically infer its lack of relevance or importance. It may well be that autonomy was considered more of a general canon in society and, like do not steal was taken as given and thus did not necessitate explicit statement. Indeed like many routine general practice examinations today, “qui tacet, consetire vedetur’ – he who is silent is deemed to have consented.

However, whether or not consent is required is no real issue of any bulk, the more complex concern is how much information is necessary for consent to be deemed informed consent. One could argue that as it is likely to be time-consuming, it is a duty that has to be balanced against other duties that also take time to accomplish. Nevertheless, though this may indeed be a neat line of reasoning it fails to provide the moral scaffolding for healthcare professionals to lean on for support when the waters become murky and unclear.

There are 3 approaches to deciding the volume of facts to impart; what would be reasonable to most doctors, what would be reasonable to most patients, and what would be reasonable to this patient in this unique consultation with this specific doctor. In British law, following the I957 Bolam vs. Friern case, the reasonable Dr. standard was adapted, often simply referred to as ‘Bolam’. However, conversely, this ruling is almost irrelevant in everyday decisions as the medical profession already acts with ‘reasonable patient’ as its gold standard, thus it is extraneous that ‘Bolam’ falls short of the European Convention of human rights. The most pertinent literature on the matter is the GMC’s 1985 “Guidance on consent: the ethical considerations” which steps far beyond ‘Bolam’ emphasizing the need to provide patients with the maximum information possible to aid them in their decision-making. This situations lack of clarity is highly relevant, should only ‘Bolam’ existed then to justify withholding information regarding a placebo prescription would be entirely excusable, provided that most other doctors would agree that it is in the patients’ ultimate best interests. [10]

Could we conceivably claim that withholding information regarding the administration of a placebo is a therapeutic privilege? The tenet exists strongly historically, from the Hippocratic ethic, “conceal most things from the patient,” to Percival’s Medical Ethics in 1803, later repeated verbatim in 1847 in the founding code of the American Medical Association, “physician should lift spirits … by revealing the severity of illness, may lower mood and thus hasten death.” This therapeutic privilege as it is known is both recognized and accepted in British law. Mason and McCall Smith observe; “even the most dedicated to patient autonomy will allow the doctor the ‘therapeutic privilege’ to withhold information which would merely prove to distress or confuse the patient.” [17]

We now approach paternalism already established to be historically favoured by those such as Plato, but a most unfashionable term in the 21st century, and that overlaps and interlinks with therapeutic privilege. Medical paternalism can be defined as preventing people from making unwise choices that may harm them. The key is choice- thus one cannot be paternalistic to an infant or someone deemed without suitable mental capacity as they would not have had the competence to make a choice, and therefore cannot be prevented from doing so. Paternalism can be subclassified into soft and hard paternalism. Soft paternalism is most famously exemplified by, “preventing a wayfarer from stepping onto a broken bridge… suggesting that restricting people’s liberty when they will otherwise act against their own true preferences is justified” [17] Hard paternalism could be demonstrated as imposing a blood transfusion on a Jehovah’s witness. Thus, as all but the most extreme are opposed to hard paternalism, if we wish to progress with the placebo it must be defined as soft paternalism.

Discussing the Doctor’s Dilemma

So whilst autonomy has had a lesser position historically, in an age where our patients have such widespread access to a wealth of (albeit dubiously accurate) information, our stance must be appropriate to the times we live in. Commonly then, we can say that informed consent in the most apposite approach in current society. Whilst not enshrined in British law, it is required by European law, so if we wish to justify withholding information in placebo prescriptions, we are going to have to discover a slant that marries it with informed consent and does not encroach on patient autonomy. Doctors today wrestle with paternalism as it is unpopular with the public, who feel that it is patronising, condescending, and insulting. Then again, medical paternalism is only insulting and a failure of respect where doctors and nurses unreasonably presume that they know better; in complex cases where years of training are pitted against the wit and wisdom of Google, it is not unreasonable to expect that those with training will be more informed than those without.

Ultimately it is our patients to whom we have to justify our decisions, if the consensus is that white lies are acceptable to improve general health, then we can justify it in individual consultations- the reasonable patient standard. We can identify general responses and attitudes to placebos by considering trial participants responses at debriefing. The conclusions drawn by a meta-analysis of debriefing in placebo-controlled trials were, “it is important to try and avoid creating feelings of embarrassment, mistrust or disillusionment, and to prevent damaging a healing repose.” Most problematically, the greater the incidence of placebo prescription leading to greater awareness may well damage the beneficial healing relationship that constitutes the effect itself. [18]

The best argument is for informed deception, the discourse between clinician and trial participant as follows, “You should be aware that the investigators have intentionally mis described certain aspects of the study. This use of deception is necessary to obtain valid results. However, an independent ethics committee has determined that this consent form accurately describes the major risks and benefits of the study. The investigator will explain the misdescribed aspects of the study to you at the end of your application.” However, this would be most difficult to adapt to the clinician-patient relationship due to differing expectations from the relationship, although promisingly if it could be adapted there was no substantial decrease in enrolment, suggesting that the placebo and deception were not found to be entirely unpalatable.

It can also be reasoned that the amount of deception involved is no greater than in everyday life and with far greater advantages. Clifford Nass, professor of communications at Stanford University, ”We spend enormous amounts of time teaching children to deceive – it’s called being polite or social. The history of advertising is all about deceiving. In education it’s often quite important to deceive people- sometimes you say ‘Boy, you are really doing great’ not because you mean it but because you thought it would be helpful.” Deception is also a problem for professionals as according to diktats of moral philosophy, moral character depends on habits of conduct. As such the use of deception in research may interfere with the disposition not to lie or deceive persons, and those who witness deception may develop skewed perceptions of the ethics of deception. [19] Is it deception that the public does not realise that every aspect of physician bedside manner is part and parcel of the placebo effect? Would it change their attitude if they knew?

Conclusion

Even with numerous caveats and ratings, armbands and escape clauses, a convincing argument can still be made that the violation of the physician-patient relationship and the destruction of trust (a rapport part and parcel of the placebo effect) means the deception can still not be justified. [19]

Nonetheless, if the placebo is used correctly it is an incredibly cost-effective tool, the problem lies in re-education as to its correct use. “Many physicians relate to the placebo as a diagnostic tool. This indicates a persistence of long-discredited notions of a separation between mind and body.” [20] As to whether the placebo is physiology or psychology the answer is categorically both. As a first-year medical student still overwhelmed with the volume and detail of human anatomy it astonishes me that there can be any question of the mind-body link. Attend any dissection it can be tracked, for the sceptics’ eye, the routes of neurons and blood vessels (containing a cocktail of controlling chemicals) from the brain to the body and vice versa. Moerman tried to re-brand the placebo effect as “The Meaning Response” and although there was much thought and evidence to support this idea, it has as yet failed to be incorporated into common medical technology. [21]

There is a growing movement towards alternative medicine, which is, after all, paternalism in a more wholesome guise, yet paradoxically within the doctor’s consulting room, there is absolute revulsion for it. “Society is increasingly dependent upon the doctor to cure-all it’s ills social, political, emotional and physical. Yet with dependence comes disenfranchisement.” Do we exhibit this resentment of our infantilisation by our obsession with informed consent? We are a culture, “which turns to the doctor as a latter-day Messiah”. [17] The benefit for an alternative medicine practitioner is the nimble sidestepping of the ethical dilemma if they can convince themselves that they believe somehow that their placebo is pharmacologically active, then there is no moral or ethical issue with telling the patient the same. Perhaps we need more publicized research and harnessing of the media to increase awareness of the placebo effect in animals to reduce the (often potent) unspoken associations with malingerers and attention seekers.

So where does the placebo truly belong? With the quacks and homoeopaths, gradually eroding public faith in science? Embraced by mainstream medicine but at risk of losing the sacred trust invested by patients in physicians? In randomised controlled trials where it is no longer relevant- (surely it is of no use to know if a drug is effective anymore, we wish to know if it is more effective than what we already have)? Perchance it best belongs in the hands of more eloquent writers and orators than I, to debate these issues across the web, the tabloids, the broadsheets, the radio and the television. It is only when the public embraces the placebo that we can negotiate the ethical pitfalls and unreservedly adopt the placebo’s medical magic.

POSTSCRIPT:

“This revealing [of] the placebo effect may be noxious to some readers because many of the medications we take rely on the placebo effect, and this effect might ‘evaporate’ after reading

… Any such harm should, however, be compensated for by the acquired diminished sensitivity to the nocebo effect.” [9]

References

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Miller A.A.D. (1973) An examination of the placebo reaction in patients attending a general practice.

M.Phil. University Of London

Dunlop E. and Weisberg]. (1968) Double-blind study prazepam in the treatment of anxiety. Psychosomatics 9 235-238
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Bergin A.E., and Garfield S.L. (1971) Handbook of psychotherapy and behaviour change: an empirical analysis New York: Wiley.

Goldacre B. (2009) Bad Science Great Britain (Harper Perennial) Harper Collins
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11 (2) 223-226

Oxford University Press (2007) Oxford Concise Medical Dictionary (Seventh Edition)

Oxford: Oxford University Press

(8] Sherman R. and Hickner J. (2007) Academic Physicians Use Placebos in Clinical Practice and Believe in the Mind-Body Connection Society of General Internal Medicine 23 (I) 7-10

Bulger R. (1991) The demise of the placebo effect in the practice of scientific medicine- a natural progression or an undesirable aberration? (Trans Am Clin Climatol Association) 285- 295
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Of America: Harvard University Press

[11] Frankenhauser M., Jarpe G., Svan H. and Wrangsjo B. (1963) Psychophysiological reactions to two different placebo treatments Scandinavia Journal if Psychology 4 245-250

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Kirsch 1985 in [IO]
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(16] Jackson]. (2006) Ethics in Medicine Cambridge: Polity Press

[I 7] McLean S. (1999) Old Law, New Medicine: Medical ethics and human rights London: (Pandora)

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[! 8] Di Blasi Z., Crawford F., Bradley C. and Kleijnen J. (2005) Reactions to treatment debriefing among the participants of a placebo-controlled trial BMC Health Services Research

5:30

(19] Miller F.G., Wendler D. and Swartzman L.C. (2005) Deception in Research on the Placebo Effect PLoS Medicine 2 (9) 853-859

[20J Nitzan U. anci Lichtenberg P. (2004) Questionnaire survey on use oi placebo British

Medical Journal 329 944-946

[21] Moerman D.E. Jonas W.B. (2002) Deconstructing the Placebo Effect and Finding the Meaning Response Annals Of Internal 136 (6) 471-476