Earlier this year, an interesting review was published in the open access journal Psychology Research and Behaviour Management. The title of the paper How can placebo effects best be applied in clinical practice? A narrative review, seems to create somewhat of a paradox. The usual definition* of a placebo is “a substance (or procedure) that has no therapeutic effect”. So, in a sense, the title of this paper could be re-written as ‘How can the effects of things that have no effect best be applied in clinical practice? A narrative review’!
In the clinic
Paradoxical titles aside, the authors suggest that there are certain principles that can be applied to enhance clinical outcomes, including:
– speaking positively about treatments
– providing encouragement
– developing trusting relationships between doctor and patient
– providing reassurance
– supporting relationships
– respecting uniqueness
– exploring values
– explaining basic mechanisms behind treatments
– communicating realistic, positive expectations regarding the outcome of treatment and the patient’s ability to cope with the disease and its treatment
– providing evidence about the efficacy of a treatment
– replacing negative suggestions with positive hints, for example, “here is your pain medicine” can be changed to “Here’s some medicine to help you get better”
-educating patients to ensure that they have a clear understanding of the treatment and the desired outcome
The authors suggest that there is evidence that these principles can have a powerful effect:
“Kaptchuk et al demonstrated this when they administered placebo without deception in patients with irritable bowel syndrome.48 They obtained placebo effects based on the relationship between patients and health workers. Further, they found that switching from a technical style to a more emotionally warm/empathetic style increased the placebo effects from 42% to 82%.”
When I read through the list above, I couldn’t help but think that it’s more than a bit daft that these principles were considered to have ‘placebo’ effects – even a brief reading of recent (psycho)neuroimmune literature will provide explanations (or at least well grounded theories) of the biological basis of the benefits of positive expectations, supportive relationships, health literacy and accurate conceptualisations of health, disease and recovery. Further, a modern understanding of pain, based on the notion that ‘we will experience pain when there is more credible evidence of danger to our body than credible evidence of safety’ (Moseley and Butler 2015) suggests that each of the listed principles could have a profound impact on reducing pain by providing powerful, credible evidence for safety (SIMs).
Time to let go?
Lorimer Moseley has suggested that the notion of placebo needs reconceptualising:
“The notion that placebo responses are responses that are evoked by nothing is nonsense… That a placebo response occurs means that something has changed the brain’s evaluation of whether or not to evoke that symptom. This makes a placebo response not a response to nothing, but to something we haven’t identified or measured.
Rather than interpreting “placebo” responses as mysterious unexplainable responses to nothing, we should, as the editorial hints, get excited about what else might have led the patient’s brain to conclude that the need for symptoms had just reduced. To suggest we should use the placebo response in clinical practice seems a bit daft to me because it is the other things (we are yet to identify, accept, or understand), which change the brain’s evaluation of the need for symptoms, that we should utilise.”
Suggesting that the ‘placebo effect’ be used clinically may well be daft, but treating a person experiencing trouble as a human being, providing up to date, reliable and relevant information, demonstrating respect, engendering trust and trustworthy relationships, and encouraging realistic hope seems like an eminently sensible approach in any clinical setting, don’t you think?
Maybe it’s time to let go, completely, of the notion of placebo. Perhaps an updated understanding of human beings means that this term is redundant, that there simply is no such thing as placebo? Thoughts, arguments, critical appraisals and even rants (as long as they are well thought out and referenced) invited in the comments below.
-Tim Cocks
Moseley GL and Butler DS (2015) 15 Years of Explaining Pain – The Past, Present and Future, Journal of Pain (Accepted manuscript, ahead of press).
* there are multiple definitions for ‘a placebo’ or even ‘placebo effects’ but this is murky territory and, to be honest, this definition just fits so much better with the rest of the piece!
Reblogged this on Fisiosofía and commented:
Must read
Excellent post. Thanks for writing and sharing your valuable insight 🙂 Cheers Kjartan
Thanks for your kind comment Kjartan.
Tim,
Really interesting conceptualizations here. I a big fan of placebo for what it exposes in human thought, bias, reaction and ability. Some comments:
1) It seems placebo has changed meanings from something akin to a sham to something non-specific that seems to boost specific efforts.
2) Sometimes placebo gets mixed into the concept of Therapeutic Alliance… or are they two wings of the same bird?
3) Are we almost to the point where we must just take placebo for granted, as a constant if you will, since placebo/nocebo effects are present in every interaction? Similar to gravity, it is always there, we can then subtract it from the equation and view the world with placebo (gravity) as an assumption.
I beleive it is very useful to behave in a manner described as “placebo.” But it, in and of itself, is not controllable enough to be wielded as treatment as a stand alone.
Great piece, gets the neurons firing… I’m going to read it again…
-Matt D
I think classical conditioning is an area that could be investigated further as part of a manual therapeutic approach.
I think when you take over another practitioners patient and it doesn’t work out as well as you hoped there will have been an element of classical conditioning as well as the therapeutic alliance and expectation in the previous relationship.
Having a slightly different approach and outlook may alter the neuro,endocrine,immune response to the treatment and reduce the effect.
Now I always take extreme care in finding out the previous therapists approach and try to use it as a basis for the treatment .
Hi info,
‘Classical conditioning’ is just expectation. Pavlov’s dogs salivated because they expected food when the bell rang. The two things (food and bell) are linked via association, but it’s still expectation. Similarly, pain can be relieved or aggravated by what we expect. Rapport intensifies the effect of expectation simply because the client is open to new ideas. 2 things – rapport and expectation. Physio in a nutshell.
I like your point about colleagues treating a client who then comes to you. It can be extremely tricky navigating around rigid belief systems created by daft therapists. A client who has experienced pain relief during an intense pummelling of the lower back will attribute the relief to the technique and the physical skill of the practitioner. Of course this is utter nonsense. But the client will always favour one approach over the other. The degree of approval will depend on rapport and nothing else. If the rapport you create with the client is greater than the other therapist, then you can easily instill new beliefs (like “pummelling is not necessary”). If not, you can’t.
EG
I enjoyed this post and find it interesting to think about placebo effect as a SIM, (or nocebo as a DIM?). However, I think some clarification about the definition of placebo is necessary. It seems to me there are 3 potential kinds of placebos we could think about:
1. Placebo effect observed in a patient receiving an effective treatment
This patient would likely improve greatly because of positive inputs listed in the post above, acting as SIMs.
2. Placebo effect observed in a patient receiving an ineffective treatment.
This patient we wouldn’t expect to improve with the given treatment, but does because of SIMs given by the practitioner, self or others.
3. Placebo effect observed with sham or control treatment.
This seems to be somewhat different than the others. Patients in a control group or receiving sham treatment often improve in research studies. It seems to me this type of placebo may lack the SIM inputs from the practitioner.
For example, if a well designed RCT was conducted comparing Kinesiology taping to sham taping in a given patient group, and this study found that the treatment group had no significantly greater improvement than the sham group, we would say that any treatment effect was due to placebo. However, this study should be blinded to the examiner and the subject. So what SIMs are present to create this effect? Is it possible that there are different kinds of placebo?
Patrick,
The whole thing is about ‘safety’, as outlined by Butler and Moseley. Safety is the ego’s primary concern and as already mentioned, the level of safety determines whether we feel pain or not. Finding useful treatments is made much easier if you view everything through this one lens.
Then we have a sort of hierarchy with safety at the top:
— Safety – Will I survive? Who will pay the bills? Am I stuffed?
— Safety is altered through manipulation of expectation.
— Expectation can be altered through words and body language (no rapport).
— The expectation of words and body language can be enhanced by adding rapport.
— Rapport itself is enhanced by any technique which foucusses attention and non-judgment towards the client.
— Rapport techniques will trigger associated positive thoughts and feelings which can cascade the whole process of healing.
So you can see that human input and rapport are desirable but not necessary. Expectation can be manipulated with a street signs which reads “95% of people with osteo-arthritis do not experience pain”.
EG
I think that I agree with most of what you are saying, but, I think if we were to remove all of the above factors you mentioned we would still possibly observe a placebo effect. Example: Group A receives treatment, Group B receives nothing. We would still expect Group B to improve somewhat because of regression towards the mean. While we can argue about whether this is caused by the subjects interaction with the examiners or participation in the research study there may still be a non-psychological explanation for the placebo effect. Ultimately the placebo effect has been defined according to psychological terms. A patient believes that a treatment will work so it does (as stated previously an example of a SIM), but are there other mechanisms at work that could be providing the placebo response? Also, if we remove pain from this equation, and talk about the placebo response as it relates only to the disease processes in conditions like cancer, viral infection, etc.
Placebo, as a descriptive term, is really a bit on the patronising side. It supposedly describes something which has encouraged a ‘placating’ of the patient’s symptoms whether real or imagined. Historically, it has been super-imposed onto outcomes where adaptive processes have probably been the critical healer. Perhaps we should stop using ‘placebo’, debunk the mystique, and replace it with ‘Idiomatic Adaptive Responses’, thus giving credit where credit is due. It might seem that, with the tsunami of medical advances we witness, and the dependency culture that inevitably creates, that patients have inadvertently lost some of their intuitive trust in adaptive corrective processes….and so the growing tendency to describe a natural process as an ‘interventionist placebo’. Patients really need to re-adapt their mindsets to not thinking that there needs to be intervention for change to occur. Operators can assist that, if they can bear to be side-lined in the process !
Dear Tim,
I think that you are missing a critical component of the “cebo” effects. It is not that a placebo or nocebo has no effect. They are called the placebo and nocebo effect! It is that the chemical or procedure in question is “inert”. The chemical or procedure could not produce, through its own direct physiological actions, any physiological change.
To talk about placebo effect and not also talk about the nocebo effect dilutes the importance of both to our ( as practitioners) and, more importantly, our patients’ abilities to control their own health status. We may not be a powerful as we think we are and patients possess more capabilities than they realize.
Are there real physiological effects produced by the “cebos”? Of course. There are some great studies documenting how the use of opioid and cannabinoid antagonists block the placebo effect. Are there probably other “cebo” pathways as well that we do not yet recognize? Of course.
I absolutely love the mystery of the “cebos”. Let’s use them as much as we can. Let’s realize, however, that inert does not mean harmless. Like any intervention, we need to know both the advantages and dangers in their use. There is the nocebo out there. In addition, at times, we do need to use procedures that are not “inert” to make physiological change. We need to know how and when to use these powerful tools correctly. TGD
Dear John
I think I’m missing your point! To wit:
“It is that the chemical or procedure in question is “inert”. The chemical or procedure could not produce, through its own direct physiological actions, any physiological change”
But later
“Are there real physiological effects produced by the “cebos”? Of course”
To talk of ‘nocebos’ would be as daft (to borrow Lorimer’s term) as talk of placebos. I take Lorimer’s point to be that the notion of some *mysterious* placebo or nocebo ‘effect’ is non-sensical – it’s just that we do not understand the mechanism (yet) so it all gets lumped under one term.
If something is truly inert how could it also be harmless – by definition if it could do harm, then surely it can not be inert? This seems to be an issue with the misconceived categorisation of a substance/procedure/thing as inert in the first place.
To suggest that a sugar pill (or other procedure/substance) is inert within a strictly biomedical framework may make limited, reductionist sense, but to suggest that a sugar pill is inert when delivered by a doctor/researcher in the environment of a hospital/facility and within the broader context of all that the individual has been told, believes, sees and does, etc etc, seems to me to be implausible from a biopsychosocial view point.
Of course, it is only my opinion (and I’m well aware of how much that is worth) but I think that the (mis)conceptualisation of placebos as something ‘mysterious’, and as ‘inert, yet powerful’, and the awkward relationship that physiotherapy has with their existence and ‘use’ has held the profession back in many ways.
My best
Tim
Yo Tim,
I am a reductionist and proud of it. If I take a medication or I institute a treatment plan on a patient, I want to have some assurance that the interventional procedures performed have some direct biological effect that is relevant to the problem. If I have a bacterial infection, I want my physician to think reductively to provide me with the most appropriate biological intervention. I understand, value, and use, both for my patients and myself, the more integrative and multi-system BPS mode. But truthfully, I want something that is not a placebo if I have a staph infection.
First of all let me explain in a little more detail the concept of “chemically inert”. What I mean and what most of the placebo literature means by that term is: that the substance (molecule) ingested or interventional procedure (surgery, exercise, dry needling, etc.) performed could not directly chemically or physically inhibit or excite any membrane receptor or biochemical pathway through its own or one of its metabolites action. The best example of this is the well-documented injection of saline as a battlefield substitute for morphine for pain control when the supplies of morphine were exhausted. There is no possible way that the sodium and chloride ions injected in the concentrations or amounts injected could have had any direct chemical effect on the nervous system. As far as the nervous system was concerned, those injected ions were inert, useless, worthless. The act of the injection, however, was not. It had a profound effect. I think that it is important in understanding the biochemistry of the placebo effect that the performance of the delivery mechanism is separated from the “substance” which is believed to be the active agent. Clearly the placebo and nocebo effects are rooted within a BPS framework.
I believe that there is sufficient evidence to state that we do understand much about the physiological pathways (the B of the BPS) through which the placebo response is expressed. Again I am operating in my reductionist mode. Finniss et al. (see the reference below) provide a fantastic review of the placebo effect in their article and should be an important reference for anyone interested in how the brain can affect the effectiveness of an intervention.
My fascination with the placebo effect exists on multiple levels. There is the whole organism (BPS) effect that is seen through the act of the delivery of an essentially biologically worthless substance. On the other hand, the physiological effects that occur as a result of the act of delivery must have occurred because some biological change on a cellular or systemic level. My reductionist mind wants to know what those changes are and how they occurred because they could not have occurred through the activity of the worthless substance. Understanding the nocebo and the placebo in relation to pain production and control is in many ways the allegory that best helps me explain pain to myself and often to my patients.
Damien G. Finniss, Ted J. Kaptchuk, Franklin Miller, Fabrizio Benedetti. Biological, clinical, and ethical advances of placebo effects. The Lancet: 375, 686-695. 2010 DOI: 10.1016/S0140-6736(09)61706-2 PubMed: 20171404
I remember an old patient who fell into a discarded mine shaft. The shaft had been improperly sealed off, and when he stumbled into it, he became well and truly stuck some 10 feet under ground.
Rescuers came along eventually and he was relieved to be able to accept a line back up to the surface. As he was being hauled up, sunlight illumined a few spots where he might have been able to gain a foothold and haul himself out. That gave him some hope that if such a thing ever happened again, self-help is always a possibility.
When he got to the surface he felt like a helpless child, completely dependent on his rescuers for his survival. He expected the rescuers to beam with pride at their achievement, but he was quite surprised. Both of his rescuers were people who had been in similar dire situations themselves. They listened to his story and recalled how they had felt similarly. Whilst neither of the rescuers offered sympathy, both of them knew exactly what he was feeling. After a few minutes, both rescuers took off their rescue gear because it was no longer necessary. In fact it wasn’t necessary at any point, it’s just that the job requires them to wear a uniform for some strange reason. The 3 blokes sat there near the mineshaft for quite some time, one on a log, one on the first aid kit and one on his haunches. The survivor noticed that each of them sat at roughly the same height off the ground, which was unexpected.
Patrick, in the example you give:
Treatment group A versus placebo group B.
Both groups will probably experience natural history effects (regression to the mean) at the same rate. That can be assumed to be fairly equal between groups, so long as they are assigned randomly. Most studies aren’t too fussed about measuring natural history, because it’s not their purpose. But when they are, they add a 3rd group C who has no intervention at all… no placebo, no nothing. It’s easy to measure and control for natural history if need be.
In terms of chronic pain, researchers would look for a stable baseline of symptom severity. From this point, regression is unlikely, therefore one can assume it’s negligible. For acute conditions, a 3rd group should always be considered, and you’re right, some forget to do this.
Thanks to all above for thoughts and comments – there’s some really good stuff in there that I’d love to respond to. However I’ve been working on a top secret project here at NOI and been mostly away for the interwebs for a few days now. Soon as I can I’ll be back.
Thanks again for reading and commenting
My best
Tim
This would seem to fit here. Somehow. http://www.nejm.org/doi/full/10.1056/NEJMp1504023