The paradigm of placebo

Is placebo a dirty word? Is it unethical?

Is place­bo a dirty word? 

Is place­bo unethical?

I have heard it described as both and I want to chal­lenge this a lit­tle further.

What is a placebo effect?

In 1955, Hen­ry Beech­ers pub­lished The pow­er­ful Place­bo’ in the Jour­nal of Amer­i­can Med­ical Asso­ci­a­tion and he out­lined the dif­fer­ence between place­bo and a dum­my’. He described a dum­my’ as the pre­scrip­tion of a medicine/​procedure/​therapy which is intend­ed to have no effect. He quotes the Oxford dictionary’s descrip­tion of place­bo quite lit­er­al­ly as a med­i­cine giv­en to please more than to benefit.

These may seem to be the same thing when per­ceived from a phys­i­cal per­spec­tive, but his arti­cle is enlight­en­ing when we delve fur­ther into the research sur­round­ing this phe­nom­e­non. A sug­ar lump that is giv­en with the inten­tion of pleas­ing rather than ben­e­fit may seem uneth­i­cal. But what if it’s as effec­tive as the a real drug or ther­a­py intend­ed for that purpose?

Raul de la Fuente-Fer­nan­dez et al pub­lished a paper in 2002 from The Uni­ver­si­ty of British Colum­bia (1). This was a Ran­domised con­trolled tri­al involv­ing patients with Parkinson’s dis­ease (PD). Half the patients were offered an injec­tion with an active ingre­di­ent and the oth­er half, a con­trol’ injec­tion of saline. This was repeat­ed twice, the first time the patients were not told which they received and as the sec­ond injec­tion was admin­is­tered the sub­jects were told which they were giv­en. Positron emis­sion tomog­ra­phy (PET) was used to study the brain dur­ing and after the injec­tions to mea­sure the amount of dopamine released by the brains. 

Humanity’s need to explain all of the ther­a­pies down to a phys­i­cal source has for­got­ten that pain goes beyond the phys­i­cal realm of understanding.

Peo­ple with PD have an impaired abil­i­ty to pro­duce dopamine, so accord­ing to the Oxford dic­tio­nary def­i­n­i­tion of place­bo there should be no dopamine release with saline injec­tions. Intrigu­ing­ly, patients who received place­bo injec­tions exhib­it­ed sig­nif­i­cant dopamine releas­es. The authors con­clude that dopamine release is linked to expec­ta­tion of a reward in this case, the antic­i­pa­tion of ther­a­peu­tic ben­e­fit.” In oth­er words, the expec­ta­tion of the reward is as pow­er­ful as the reward itself.

Could you imag­ine the poten­tial of cre­at­ing heal­ing with­out the need for nasty side effects? Which would be more ethical?

This brings into ques­tion whether it is uneth­i­cal to refuse a treat­ment when there is anec­do­tal ben­e­fit despite a lack of evi­dence (per­ceived non-ben­e­fit) There is well estab­lished evi­dence to show no cor­re­la­tion between tis­sue dam­age and pain or even bio­me­chan­ics and pain, so what do we think is actu­al­ly hap­pen­ing when we deliv­er rehab, exer­cise or a pro­ce­dure in line with cur­rent guide­lines? Are we naïve enough to reduce an expla­na­tion down to sim­ply a phys­i­cal rea­son­ing? Is there place­bo in every­thing we do?

This also opens a ques­tion of con­trol groups used with­in research. It has long been believed that the admin­is­tra­tion of a pro­ce­dure with no ben­e­fit can be com­pared to an active treat­ment to mea­sure effect. If the above men­tioned research shows that control/​placebo ther­a­py might actu­al­ly have a sim­i­lar heal­ing effect as the active treat­ment, we ought not to com­pare treat­ments to a control/​sham treat­ment and instead rely more of the anec­do­tal evidence.

the expec­ta­tion of the reward is as pow­er­ful as the reward itself

Per­haps this is also why the Cochrane reviews reveal such a lack of high qual­i­ty evi­dence with rehab and med­i­cine for heal­ing. The research does not always cap­ture the behav­iour seen clinically.

If we con­sid­er the his­to­ry of med­i­cine, rehab and sport, we may all remem­ber the fre­quent use and anec­do­tal suc­cess of ultra­sound machine, ankle strap­ping and the mag­ic sponge. Despite the ultra­sound machine not being turned on, the tape being inef­fec­tive after 10 min­utes and a sponge not seem­ing to do any­thing on a sci­en­tif­ic lev­el, they all had some suc­cess in help­ing peo­ple to over­come pain. Humanity’s need to explain all of the ther­a­pies down to a phys­i­cal source has for­got­ten that pain goes beyond the phys­i­cal realm of understanding.

With­in the sci­ence of chron­ic pain, the under­stand­ing of Cor­ti­col remap­ping shows us that the pain expe­ri­ence may reside with­in the brain and not with­in struc­tur­al deformity. 

Giv­en this, I won­der whether place­bo treat­ment might have inter­est­ing effects on the brain that we saw with­in the British Colum­bia study for peo­ple with mus­cu­loskele­tal or chron­ic pain?

Sure­ly there is place­bo in every­thing we do?

Per­haps expand­ing on the British Colum­bia paper allows us an insight into the poten­tial we all have for heal­ing when we look beyond the phys­i­cal. Per­haps our suc­cess in cre­at­ing a heal­ing envi­ron­ment has a lot to do with the con­fi­dence, com­pas­sion and kind­ness we take into the exchanges we have with clients and patients. A research arti­cle from The Pain Clin­ic in 2000 revealed stereo­types held by med­ical pro­fes­sion­als towards patients expe­ri­enc­ing a painful med­ical procedure(2). 

It revealed that the major­i­ty of med­ical pro­fes­sion­als per­ceived old­er and less attrac­tive patients to expe­ri­ence less pain than those who were younger and more attrac­tive. What sort of com­pas­sion and kind­ness might a med­ical or exer­cise pro­fes­sion­al dis­play towards patients that they per­ceive as old­er or less attrac­tive? If we con­sid­er the 2002 British Colum­bia paper, which teach­es that the expec­ta­tion of the reward is equal­ly pow­er­ful as the reward itself, it may be worth invest­ing in the meta aspects of heal­ing rather than pure­ly the physical.

References

1. Fuente-Ferna´ndez R.D.L, Phillips A.G, Zam­burli­ni M, Calne D.B„ Ruth T.J, Stoessl A.J. (2002). Dopamine release in human ven­tral stria­tum and expec­ta­tion of reward. Behav­iour­al Brain Research 136: 359363

2. Thomas Had­jis­tavropou­losDiane LaChapelleCar­la Hale & Far­ley K. MacLeod (2000). Age- and appear­ance-relat­ed stereo­types about patients under­go­ing a painful med­ical pro­ce­dure. The Pain clin­ic: 12(1).