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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12 responses so far

12 Responses to ““The” Placebo Effect Proven?”

  1. benshumson 26 Oct 2009 at 9:57 am

    Good article! :D

    What area of medicine has the strongest physiological placebo effect aside from pain? In other words, since pain is the most physiologically active placebo, what placebo is the ‘second’ most physiologically active?

    Looking forward to someone’s answer/opinion….
    Science is the shizzle ;-)

  2. jonny_ehon 26 Oct 2009 at 10:45 am

    (I was going to post this comment at skepticblog.com but it didn’t work, sorry if it appears there later too)

    If we can’t use the term “the placebo effect” to describe the phenomenon of the ‘mind over matter’ effect, where the act of thinking a treatment will help, causes it to work, then what term should be used?

    I’ve understood it that this is the placebo effect, and the other phenomena you described that the placebo group controls for are just other confounding factors. In other words, the placebo group controls for the placebo effect, plus other effects that can occur.

    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

    Here you refer to all confounding factors as placebo effects yet according to Bausell’s “Snake Oil Science” and Singh/Ernst’s “Trick or Treatment” the mind-over-matter type of confounding factor is “the placebo effect”. Bausell even talks about a study where researches were able to block “the placebo effect” using opioid blockers. He had clearly separated the placebo effect from other confounding factors. I apologize if my terminology is off, I’m not a doctor/scientist.

    I realize this is a debate about semantics (the definition of “the placebo effect”), but this is an extremely confusing area therefore consistent and clear terminology would help immensely.

    I’m also curious if all the doctors in the skeptical community are in agreement on its definition. You can see here some debate about what the placebo is on sciencebasedmedicine.org (look in the comments).

  3. Eternally Learningon 26 Oct 2009 at 12:05 pm

    Maybe “The Placebo Effect” is kind of like “Gay.” “Gay” may literally mean happy, but the cultural meaning has changed so much that it makes clinging to the originaly meaning a losing and pointless battle. Perhaps someone needs to coin a new set of self-explanitory phrases to describe these effects?

  4. Watcheron 26 Oct 2009 at 12:32 pm

    The actual title of the paper is “Direct Evidence for Spinal Cord Involvement in Placebo Analgesia” which makes that demarcation, in my opinion anyways, you are talking about Steve. But that was your point too :) Unfortunately, it seems like poor writing that could have been cleared up by a 5 minute one-on-one over the phone with the PI.

    Another beef I had was that the New Scientist article says it narrows the effect down to cells, which looking at the data, doesn’t actually do so. The authors do not go into detail about it other than to say it was found in the dorsal horn, an area thought to be involved in early nociception mediation. Infact they say:

    However, our study cannot reveal the exact mechanism of spinal inhibition [i.e., effects on primary afferents (presynaptic), interneurons, or projection neurons (postsynaptic)] and whether the observed effect is specific for nociception, because we did not measure responses to innocuous stimuli.

    Very cool study though. It’s nice to see/have data that shows this placebo acts in a physiological manner. I see it as a good foot in the door for further studies.

  5. Steven Novellaon 26 Oct 2009 at 12:51 pm

    Yes – good study, bad reporting. I here the “placebo analgesia” phrase used a lot in the technical literature. I think the misconceptions are mainly with the public, and that is where science reporting should be closing the gap, not feeding into the confusion.

  6. Steven Novellaon 26 Oct 2009 at 4:41 pm

    There is no one consistent definition for the placebo effect, so it is used in various contexts and this causes confusion.

    I have read more careful texts that refer to the “analgesic placebo effect” or “placebo effect for pain” to be more specific.

    Keep in mind, as I wrote – there is an operational definition for “placebo” in clinical trials. This is -the effect measured in the placebo arm of the study. That is considered as the placebo effect for that study, and the effect of the treatment is the difference between the treatment arm and the placebo arm. That “placebo effect” is, as I said, everything but a physiological response to the treatment. It contains confounders and non-specific effects.

    The problem comes from equating the measured placebo effect in a clinical trial (everything but the treatment effect) with the mind-over-matter placebo effect. And also from equating placebo effects for subjective symptoms, like pain, especially where there is a known mechanism of mental modification – with disease outcomes where there is essentially no placebo effect other than confounding factors.

  7. daedalus2uon 26 Oct 2009 at 7:34 pm

    There is a new story on a woman (Desiree Jennings) claiming a vaccine injury due to a seasonal flu vaccination, 10 days later she has what is being called dystonia. She cannot walk, but is able to run, and can walk backwards. There are a number of videos of her available.

    Generation Rescue is coming to her “rescue”, as “experts” in vaccine injury.

    At least one expert said her symptoms looked psychogenic.

    http://www.youtube.com/watch?v=Qo-cIP3VBfo&feature=player_embedded

    There is a thread on it over at skepchick

  8. BigHeathenMikeon 26 Oct 2009 at 8:46 pm

    Articles like this make me want to have a network. You know, like that Verizon commercial where the dude walks around with a couple hundred people behind him. Then, when some altie spouts nonsense that I know is wrong but can’t explain properly, I could just turn around and say, “Hey network, where’s Dr. Novella? I need him to talk about the placebo effect.”

    There would be much discussion.

    Thanks for this and all the great work.

  9. HHCon 26 Oct 2009 at 9:56 pm

    daedalus2u, Do you think this could be a psychogenic, dyskinesia for Desiree Jennings? I question what kind of hazing this Washington cheerleader was exposed to as part of her training. Which drugs, other than the vaccine, or what kind of physical traumas did she have exposure to at home or at the training sites?

  10. eiskrystalon 27 Oct 2009 at 5:08 am

    It’s theory and scientific theory all over again.

  11. daedalus2uon 27 Oct 2009 at 8:46 am

    HHC, those suggestions are beyond my expertise which is why I tried to bring it to Dr Novella’s attention because it covers several areas where he has both expertise and interest.

    I suspect that the anti-vax groups will to try and turn her into a cause célèbre, and perhaps even try to exploit her as a legal case against the flu vaccine, or as an anecdote of “recovery” for what ever quack treatments they use on her.

  12. sonicon 27 Oct 2009 at 2:00 pm

    The first line of the article-
    “The placebo effect is not only real; its ability to deaden pain…”
    So the placebo effect has abilities now? This is very sloppy writing and/or thinking.

    How much is the placebo effect related to inattentional blindness as you covered recently?

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