The Mysterious Vanishing Placebo Effect?

I have written about the placebo effect before, but a recent update to a Cochrane review entitled Placebo Interventions for All Conditions has prompted me to revisit the subject. It has been clear for some time that the so-called placebo effect is not an example of the power of the mind to overcome disease. There is no evidence that therapies which have no measurable biological affect can truly alter the progression or outcome of an illness. No matter how you feel when given a deliberate placebo or an inert CAM therapy, you don’t live longer, your tumor doesn’t get smaller, you blood sugar doesn’t become normal, and the objective effects of your disease on your body don’t change.

What has seemed reasonable to me in the past is the idea that there might be real benefits in terms of subjective symptoms, such as pain or nausea, attributable to placebo effects. However, I am a little less confident of that in light of this recent review.

The review was a metanalysis of clinical trials which included both placebo and no treatment groups. As expected, no significant clinical effects were found for any objectively measurable variable. However, even in the case of subjective variables like pain and nausea, the best the authors could say was, “in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting.”

For pain, some trials reported little or no effect, and those that reported a large effect were all conducted by the same group of researchers, which raises suspicions about the reliability of the findings. Findings for most other subjective measures either showed no benefit from placebo, or effects that varied enormously from one study to another, suggesting differences in the studies were responsible for differences in the findings. If the placebo effect were a consistent, reliable phenomenon one would expect it to show up about the same regardless of who is studying it.

The metanalysis also found that how much benefit patients seemed to get from placebo treatments depended heavily on whether they thought they might be getting a placebo treatment. Inert treatments worked better in trials where the subjects were told that no placebo would be given.

These findings and others like them make it seem very likely that the placebo effect is less a feature of the human mind than it is an artifact of  clinical trial design, a conglomeration of biases and measurement errors rather than mind over matter. The better one controls for biased reporting of effects, the less effect one sees. This is not how the results look when one studies an unequivocally effective therapy, even one involving subjective symptoms, such as NSAIDs for arthritis pain. Effects from real therapies are consistently seen in different studies by different researchers, and they do not disappear when the trials become better controlled for bias.

Of course, if someone tells you they have pain or nausea, and then you give them a placebo and they say they have less pain or nausea, can you really say the effect isn’t real? If these phenomena are ultimately subjective, than regardless of the biological events underlying them the perceptions of the sufferer must be the critical determinant of benefit. Still, most of the research on placebos and sham therapies suggests that when well-designed studies are conducted, these benefits are small and do not reach anything like the level of clinical significance of true therapies for these symptoms. And, as I have discussed before, taking advantage of what benefit may occur due to placebo effects requires successfully deceiving the patient, which raises significant ethical concerns.  The lesson of this review seems to be that placebo effects may turn out to be mostly illusory, artifacts of inadequate study design, and we should be hesitant to rely on them for treatment of any clinically significant symptoms.

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2 Responses to The Mysterious Vanishing Placebo Effect?

  1. Kolmashekidim says:

    No broad disagreements with this post, but excuse me, isn’t the following a non-sequitur?

    ” Inert treatments worked better in trials where the subjects were told that no placebo would be given.

    These findings and others like them make it seem very likely that the placebo effect is less a feature of the human mind than it is …”

    This is exactly what one would expect if the placebo effect were a feature of the mind. Believing the treatment is real makes it more likely to be effective even if it is not real – that’s the placebo effect, right?

  2. skeptvet says:

    Thanks for the question.

    The way I interpret the finding that placebo effects are greater when subjects believe no placebo allocation is possible is that the subjects are more likely to respond to interrogation as if they are receiving a real treatment when they believe they are. This point I was trying to make, obviously not very clearly, is that this does not imply their symptoms or disease actually improve as a function of their belief (the old, mind-over-matter theory of placebo) but simply that their beliefs affect how the interpret or perceive their symptoms and how they report them to researchers.

    I think this is an important distinction. One of the justifications for using treatments not clearly proven to work is that even if they are inert in themselves, the placebo effect they exert could mean real, meaningful improvements in the patients because beliefs can affect bodily disease and its symptoms. I think it is more likely correct to say that beliefs affect how we view and talk about our disease and symptoms. If people believe they are receiving a real treatment, expectation, cognitive dissonance, and other features of how we evaluate our experiences may lead them to imagine they are better or to report improvement where none really exists. If they suspect they might be in a placebo group, even if they aren’t sure, this makes it harder for them to imagine improvements that aren’t really happening because the expectation that they are getting real treatment and so should improve is weakened.

    Of course, as I pointed out in the post, it is impossible to say that perceived improvements in completely subjective symptoms like pain aren’t “real.” But in general, I think the evidence is beginning to point not to a real benefit from belief so much as an influence on evaluation and reporting of subjective symptoms which creates the impression of such, which is quite a different thing. If this is so, then the placebo effect is, of course, a function of mind in the sense that all beliefs are, but NOT in the sense of mind affecting bodily disease in a real way, which is how it is often understood.

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