Oct 26 2009

“The” Placebo Effect Proven?

A recent study, as reported in the New Scientist, purports to catch the placebo effect in the act using functional MRI scanning. This is an interesting study, and does for the first time show a neurophysiological correlate to reported placebo decreases in pain reporting.

However, reporting of the study highlights, yet again, widespread misconceptions about the nature of placebo effects – specifically that there are many placebo effects, not one placebo effect. Any reference to “the” placebo effect is therefore misleading – it is a convenient short hand, but unfortunate given prevailing misconceptions.

What most people mean when they say “the” placebo effect is a real physiological effect that derives from belief in the effects of a treatment – a mind-over-matter effect. However, the placebo effect, as it is measured in clinical trials, has a very specific operational definition. It is any and all measured effects other than a physiological response to the treatment itself.

This includes any physiological responses to belief in the treatment, but also a host of psychological factors such as reporting bias, confirmation bias, risk justification, and assessment bias. It also includes non-specific effects of being in a clinical trial – people treat themselves better when they are being observed, when they are being reminded of their illness because of frequent attention, and when they are encouraged by the hope of benefit. Such things actually affect compliance with other treatments and healthy lifestyles – in other words, people will be more compliant with other medications they may be on, and may eat better and exercise more, etc.

These variables and others are the reason for double-blinding experiments. Without doubling blinding, these placebo effects will be mixed in with the physiological effects of the treatment, if any.

Also – many people incorrectly conclude that “the” placebo effect cannot exist in small children or animals, but this is profoundly incorrect. Placebo effects result from observer bias as well – from whoever is interpreting the effects of the treatment on an animal.

It must also be pointed out that measured placebo effects differ greatly depending on the disease and the outcome being studies. The greatest effect is for pain, typically from 25-35%. This makes sense in that pain is a subjective experience and subject to a host of modifying factors, such as mood and expectation. But also, it has been known for a long time that there exists in the body natural opioids called endorphins that bind to receptors and inhibit pain, the same way the most powerful pain killers do. Therefore there is a known physiological mechanism by which mental effects could inhibit pain.

Another area where there is a strong placebo effect is any disease that is worsened from psychological stress, such as the risk of heart attacks. Any intervention, or just the act of being treated, that might reduce stress therefore has a known physiological mechanism by which disease can be mitigated.

But for other diseases, where there isn’t a known physiological mechanism, measured placebo effects are much smaller. Perhaps the most dramatic example of this is cancer survival.  Here we have an aggressive disease and a very definitive outcome – death or survival. It turns out there is practically no placebo effect when it comes to cancer survival.

And here is the real problem with conflating all placebo effects as if they were one giant mind-over-matter effect – people think because there is a large and provable placebo effect for pain, there is therefore a large and provable placebo effect for everything, and that this is evidence for some mystical mental effect over the body (in the absence of known physiological mechanisms).

This brings us to the current study. What the researchers did was look at an experimental model of pain – heat applied to the skin. They then compared an analgesic cream to a placebo cream, and subjects reported about 26% less pain even with the placebo cream (right in the middle of the typical placebo response to pain). This is nothing new, but they also looked at the spinal cords of the subjects and found that the placebo pain responders had a decrease in the signal in the pain pathways similar to the response to the actual painkiller.

The press is making it seem as if “the” placebo effect is finally proven – typically missing all of the nuance of this issue. However, while interesting, this study does not really add much new to our understanding. We already knew about the placebo effect for pain, and the prevailing hypothesis is that it was due to endorphins, and therefore we would expect an actual decrease in pain signals in the spinal cord. This study confirms it – but doesn’t change our thinking about it. Also, the study did not in any way investigate the mechanism of the decrease. We assume it is from endorphins, but that’s it.

This is not to knock this study in any way – just reporting about it. It is a nice proof of concept, and opens the way to further studies to look at which brain areas are involved in placebo effects for pain. It would also be interesting to see if there is any difference in brain activity between placebo responders and non-responders. This may even lead to ways in the future of optimizing pain placebo effects, or triggering them non-pharmacologically.

I think it is important to make these distinctions regarding the placebo effect because it is so widely misunderstood and this confusion is exploited to support all sorts of unscientific and even harmful medical modalities and interventions.

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