Placebo

[Graham Lappin]

I have just read a really good account of some studies into the placebo effect. The work was carried out at the Center for Neurobiology of Stress, University of California in Los Angeles (Clin Pharmacol Ther 86(4) 352-354).

The upshot is that they used MRI and PET scans to look at activity in brain in volunteers given a variety of treatments, some of which were placebos. I can't see anything in the article that specifically says these were double blind studies but I suspect they were (the CPT journal is a bit fussy about these sorts of things). There is indeed a cerebral response when placebos are administered and even certain aspects of brain chemistry are affected. For example PET can be used to measure dopamine receptor binding in the brain.

The placebo effect has been known, of course, for a long time but it is interesting to see that some real mechanistic based research is being conducted into the effects.

Now I will play Devil's advocate here and present the following reasoning:

A placebo can be shown to elicit a physiological response
CAMS such as homoeopathy are placebos
Homoeopathy is therefore likely to elicit a physiological response, which shows that it is an active therapy.

Sure, homoeopathy when tested against a placebo fairs no better but that's like testing aspirin against aspirin.

Is there an argument for using the placebo effect as a therapy and if not, why not?

(One more for the road)

[Matt]

Is there an argument for using the placebo effect as a therapy

yes,

the problem is ehtical - informed consent for placebo is tricky although...

[Pebble]

Is there an argument for using the placebo effect as a therapy and if not, why not?

(One more for the road)

One consistent feature of well conducted trials is that the control group do much better than would be predicted from observational data. It matters not whether they receive placebo or not. They live longer, feel better, can exercise more and have fewer symptoms.
While the contributory factors are doubtless complex, being 'cared for' probably plays a substantial role.

The issue then is how to demonstrate that the supposed placebo effects are distinctly different from the sense of well being and subsequent physiological consequences of in effect empathy.

Alt practitioners often cite their 'holistic' approach, which may well simply reflect this aspect. The real question may be how to deliver the needs of individual patients in terms of feeling cared for, as this will vary from patient to patient.

If this construct is correct then placebo or most alt med approaches are like religion, substituting magical thinking for understanding. This ultimately would simply prevent real progress.

[Graham Lappin]

.... If this construct is correct then placebo or most alt med approaches are like religion, substituting magical thinking for understanding. This ultimately would simply prevent real progress.

From the article I read, I am not sure what you are saying here is really correct. The Californian group are reporting measurable mechanistic outcomes from administration of placebos. Surely this is not magical thinking this is good science. Our understanding of the placebo effect in terms of cerebral function and brain chemistry is currently very rudimentary but as this grows, as I am sure it will, is there any reason why the placebo effect cannot become part of mainstream evidenced based medicine?

.... the problem is ehtical - informed consent for placebo is tricky

This is a difficult question but what is and is not ethical is something society decides upon. What was ethical in 1965, might not be viewed in the same way now - and vice versa.

If the placebo effect can alleviate suffering, then is it ethical to withhold its use? Tricky one, I admit.

[Pebble]

From the article I read, I am not sure what you are saying here is really correct. The Californian group are reporting measurable mechanistic outcomes from administration of placebos. Surely this is not magical thinking this is good science. Our understanding of the placebo effect in terms of cerebral function and brain chemistry is currently very rudimentary but as this grows, as I am sure it will, is there any reason why the placebo effect cannot become part of mainstream evidenced based medicine?
.

The question is what efforts were made to ensure that the changes observed with placebo administration could not have been equally induced by a simple reassuring conversation.

[Floppit]

I posted some time ago asking whether the placebo data that builds up over time with well researched diseases is ever meta analysed. I was curious whether it would give insight regarding what areas of clear physical disease show clinical improvement through placebo effect. It wouldn't matter hugely whether the effect was placebo or care and attention as much as it might matter to pull together and make sense of the 'throw away' placebo results that surely must have built up over the years.

Reading the debates in the osteopath thread the extent to which DBRCTs are needed even for very 'measurable' disease (probably wrong word but hope you know what I'm getting at), would suggest the power of psychology over the body is well recognised.

I've probably made a hash of writing that - I'm not with it today!

[Tony Williams]

I find this a fascinating subject, along with its obverse, the nocebo effect (which might more colourfully be called the witchdoctor effect). There are a few documented cases in the west of people who were told they were terminally ill dying as expected despite having nothing physically wrong with them.

There can be no doubt that the mind has a powerful effect on the body and that someone who believes in homeopathy will probably quite genuinely feel better after being treated by a homeopath. I do agree that most of the reason for that is probably the time taken by the homeopaths to talk sympathetically with their patients. There is something soothing about being cared for.

The real danger of placebos like homeopathy is when people think they can cure physical conditions such as diseases. I have the impression that they seem to do fine with the majority of complaints for which there is no verifiable physical cause - e.g. aches, pains and mild depression.

[Graham Lappin]

The question is what efforts were made to ensure that the changes observed with placebo administration could not have been equally induced by a simple reassuring conversation.

The article in CPT was not a full research paper rather than a general review. I really wish I had the time to go through the literature on this but I have pressures of work elsewhere. I certainly accept the question however, and for now all I can say is that the group reporting on the work and the journal are very much world class.

I posted some time ago asking whether the placebo data that builds up over time with well researched diseases is ever meta analysed.

Not my area and so I don't know. It's about 3 am where I am and so I am going to admit I am too lazy to go back through the posts to see if you got an answer. Nevertheless, there are clinical trials with a clinical outcome (however it is measured) and then there are mechanistic studies. The latter is more in my line. For example, a pharmacokinetic study measures the amount of drug in the body over time. This is a parameter independent of anything the subject might tell you and these types of studies are run without placebo or control groups. I am a little bias I know, but it's mechanistic studies that tend to get my attention. The placebo study I mentioned above is a mechanistic study that measured changes in the brain with PET and MRI. Pebbles point still stands in that the study has to be controlled as not to confuse cause and effect, but the outcome is at least a measure other than asking "do you feel better".

The real danger of placebos like homeopathy is when people think they can cure physical conditions such as diseases. I have the impression that they seem to do fine with the majority of complaints for which there is no verifiable physical cause - e.g. aches, pains and mild depression.

Even so, if placebos can genuinely alleviate suffering I don't think their use can be dismissed too easily.

I hope I am not being misunderstood here. I am not for a moment trying to defend the snake oil merchants. My intentions are really about the science of the placebo effect which is difficult to study admittedly. There is a danger that some self deluded nutter tries to cure cancer with placebo (happens all the time). I would argue however that the placebo is like any other therapy, it has to be used in the right way. You could cure something like AIDS with a placebo, but then again if a doctor prescribed aspirin as an AIDS remedy, this would be equally as inappropriate.

Back to get some sleep I think!

[Tony Williams]

You could cure something like AIDS with a placebo, but then again if a doctor prescribed aspirin as an AIDS remedy, this would be equally as inappropriate.

Did you mean to post that or did tiredness cause you to miss out a "not"?

[Graham Lappin]

Did you mean to post that or did tiredness cause you to miss out a "not"?

The word "not" has only got 3 letters but it has a very powerful meaning. Sorry - rewind .... You could NOT cure something like AIDS with a placebo.

It's now 5:30 am and I'm off to catch a flight from Los Angeles (where I am currently) back to DC. I think I will refrain from posting until I catch up on some sleep.

[Bob Lloyd]

The problem with placebo is that it is indistinguishable from the expectation and conditioning response. In other words, when we decide to move a finger, the brain reacts before we are even aware of the intention, and there are changes in the brain chemistry in the region associated with the movement. When the movement actually occurs, the brain compares the expectation with the actual event. That's how our mental model of the physical world is updated.

The placebo effect is closely related to this. A patient both has the expectation of treatment and is conditioned to believe it will benefit them. The brain will then react to any treatment session with changes in neurochemistry consistent with receiving real treatment, even when there is none. So the patient reports that they feel better. Simon Singh and Edzard Ernst reported the trial of telescopic (i.e. fake) acupuncture needles (developed by Ernst) which produced precisely the placebo effect - the expectation was sufficient to generate the positive placebo effect.

Unfortunately, two things make it unsuitable as a treatment. The first is ethical: placebo only works if the patient is consistently lied to and continues to believe it - they have to believe they are getting effective treatment when they are not. The second is far more pragmatic: it seems that only 30% of us are susceptible, that it isn't consistent, and it can disappear at any time. The bottom line is that placebo can convince patients that they feel better without them being better.

Patients can genuinely believe they are getting better when in fact they are not. They can also (through the nocebo effect) believe they are unwell when in fact they are improving. That shows that the mental model (affected by placebo) need not be consistent with the physical model (affected by real treatment).

Colin Frith's book Making Up the Mind is very interesting about the distinction between these two models and how our brain chemistry changes during expectation.

I've put a short article about placebo at: http://www.leavingthelandofwoo.com/d...bo-effect-work which might be of interest.

Also interesting is how Woo practitioners become convinced themselves that they are doing good by the placebo effects reported by their own customers. This accounts for a lot of the sincere commitment of Woo practitioners.

[chaggle]

I wonder if this is the reason that some GP's prescribe homoeopathy. As has been said it would be unethical for a doctor to effectively lie and give a patient a placebo, but homoeopathy seems to bypass this. There doesn't seem to be the same reticence to lie where homoeopathy is concerned for some reason.

Perhaps homoeopathy is actually useful in some cases. In this recent article for example

GPs told not to prescribe antibiotics for coughs and colds

Family doctors are to be told to stop prescribing antibiotics for coughs and colds because overuse is contributing to the spread of hospital bugs and putting vital treatments under threat.

The ECDC acknowledged that part of the problem was caused by pushy parents who demand medicine for their children.

“The BMA has been campaigning for years to discourage inappropriate use of antibiotics. This means two things – patients should not ask for them when they are not needed, and GPs should not give them."

Perhaps Doctors prescribing a homoeopathic remedy would satisfy the patients' need to be prescribed something.

[asthmatic camel]

chaggle, I vaguely recall a doctor being admonished for using the acronym TEETH in some patients' notes. Tried Everything Else, Try Homeopathy.

[Graham Lappin]

Bob Lloyd: You make some very good arguments and on balance I probably agree with you. I want however, to give you some counter arguments:

I am not sure your account of the placebo effect is really that straightforward. Ben Goldacre tells of the story that even when some people are told it is a placebo, they still feel better. The causes of the placebo effect can vary. For example in the article I started this post with, the researchers try to distinguish those effects due to conditioning. For example, if they had previously taken a red pill (which contained an active drug) and their pain was relieved, then taking a red placebo had the same effect (I have simplified).

Another example comes to mind. Many of us would have become ill after eating or drinking something. Perhaps food poisoning, or in my case being very ill drinking cider when I was 16. Face the same food again, and then there is a conditioned response of nausea. There is no rational reason that the food will do us any harm second time round but there are some very good reasons we have evolved not to give it a second chance. This may well be the same type of neuroprocessing that is going on with the placebo effect.

Any medical intervention has to be used in the right way - anything that is sold as a "cure all" is immediately suspect. If the placebo is used as a genuine medical intervention then it should be done so by professionals and in the appropriate way. If someone suffers from chronic pain where the cause cannot be located and the placebo alleviates that pain, then the underlying cause is probably psychosomatic so why no "cure" it psychosomatically? It may only work in small percentage of the population and it may not be sustainable but if that was a criterion for all medical treatments then a lot of them would disappear overnight.

I do accept they are some very dodgy ethics in all this and that, to me, is the big stopper to using sugar pill cures, even by the medical profession. On the other hand, there are those that would argue that if a doctor prescribed acupuncture under certain situations, then there might be real benefit to that particular patient.

We can dismiss acupuncture (and the like) as being woo medicine (because it is) but if there are those that get real benefit, and I think there are, then I ask if we as sceptics are not getting entrenched in the rationality and forgetting a separate, if more complex ethical aspect that suffering is suffering if it can be alleviated, even psychosomatically, should we not stand aside and let it happen?

By the way, another

[Bob Lloyd]

Bunny: I'm familiar with the Ben Goldacre red pill placebo story, but I think it is consistent with the anticipation/conditioning model. Because we are socially conditioned to regard certain colours as indicative of certain potential, we react to them as well as the expectation of getting treatment. The placebo effect is a complex combination of all of those anticipations, expectations, and conditioning. It's not just the simple anticipation of the treatment. That's something that adds to its instability as any kind of treatment.

You raise the interesting point of how medical practitioners ought to behave when the use of placebo might bring about a positive effect. The evidence seems to suggest that sympathy and encouragement alone produces the same changes in neurochemistry, and if that is born out by clinical trials, then there is an ethical alternative to telling the patient lies. It's the old bedside manner stuff. Being honest and caring, it seems, will work every bit as well as the dishonest Woo stuff, and doesn't create any ethical dilemmas.

The problem with psychosomatic cures for psychosomatic problems is that it doesn't address causs. Usually psychosomatic illnesses are actually addressed by getting patients to understand the psychosomatic origins, perhaps anxieties, negative feelings, distrust, fear, etc. Addressing those is a far more productive way of dealing with the problems than to add another layer on top. And you're right, that if medical treatments were as inadequate and unpredictable as placebos, they'd be dropped. And those that fall into that category are. There are loads of treatments that are dropped because of lack of evidence of efficacy. Unfortunately, treating psychosomatic illness is time consuming and probably the easier route is to send the problem to say, an acupuncturist, letting someone else deliver the placebo.