Tuesday 26 July 2011

The placebo effect

This post probably best falls into my other musings description of this blog. Don't however assume that it does not tie into autism or other developmental conditions though, as will hopefully be revealed.

Placebo, aside from being a band, refers to a sham intervention, normally medical, provided during an intervention study. Normally just a sugar pill or some other similarly innocuous substance or intervention, the placebo is designed to act as a control, a standard against which a proposed efficacious compound or substance or intervention is tested. To boil it down, it works something like this:

  • Compound A is a proposed treatment for condition X. Compound A is made into a tablet or something similar and submitted for experimental testing. 
  • Compound B is a placebo with no claim or connection to condition X. It is also formulated into a tablet exactly the same as compound A in appearance, smell, taste, etc
  • During an experimental trial, patients are, without knowledge of which, either allocated compound A (experimental treatment) or compound B (placebo). 
  • The effects of compounds A and B are compared. 
  • Should compound A show some effect for condition X, one would expect significantly better results compared with compound B, the placebo.

There are various other ways of using a placebo during such experimental study (the cross-over study, comparing more than one treatment option). You can perhaps see how placebo should provide a gold-standard for such trials and how confidence should be high from any changes obtained against placebo. Simple. Well, not quite...

One of the possible side effects of using a placebo is the so-called placebo effect, whereby a proportion of participants given a placebo actually report an improvement in their symptoms. A recent paper illustrating the placebo effect in action is this one comparing St. John's wort, an anti-depressant and a placebo in the treatment of mild depression. The results of the study by Rapaport and colleagues not only suggested that SJW and citalopram could not be separated by significance as the best treatment course for mild depression, but that a placebo, a sham intervention, a sugar pill, actually improved some of the symptoms of mild depression at a rate similar to that found in the more recognised treatment modalities.

Similar results from the placebo effect have been reported with regards to pain management, hypertension, asthma and even Parkinson's disease.  Little wonder that the humble placebo has been touted as a potential treatment option for various things (not that I am recommending this option).

The question of how and why the placebo effect works is a little more challenging. There is a strong case for some brain-related changes following invokation of the placebo response. Having said that the precise areas involved (note the plural areas) remain under investigation. Mind over matter probably plays a hand, or at least the effects that a little knowledge and social expectation might bestow on reported health. Apparently the ideal placebo effect involves giving more than one placebo (two pills), branded by a well-known pharmaceutical company on the pill, for the treatment to be perceived as expensive, accompanied by information and direction, from a doctor wearing a white coat, on their proposed positive effects.

How does this all tie into autism?

Placebos have been used quite extensively as part of autism research. My post a few days back on the use of levocarnitine is a good example of placebo in action. With regards to the placebo effect in relation to autism, the information base is slightly lacking. Lisa Jo Rudy discussed the placebo effect in relation to autism in a post a few years back. As she pointed out, the placebo effect might be attenuated by lots of different factors such as age, and certainly might not be as strong in younger children with autism as older children as a result of differences in things like experience and expectation. I have to say that age independent of autism is still under investigation when it comes to the placebo effect. This meta-analysis of drug resistant epilepsy suggested that the placebo effect was actually magnified in children compared to adults.

I do wonder how such age differences might manifest themselves in relation to a developmental condition like autism. So, is any placebo effect moderated by cognitive-intellectual development or social development? Would any placebo effect be moderated by the presence of comorbid learning disability? Interestingly I have not been able to find very much looking experimentally at such issues. Assuming that there is a social aspect to the placebo effect ("this pill will reduce your symptoms"), young adults with high-functioning autism, are at least as likely as non-autistic controls to act on social cues as illustrated by this small study on magic and sleight of hand. So conceivably the placebo effect might be as strong in autism as that seen in not autism?

There are quite a few philosophical issues raised by the placebo effect. Placebo used as part of our yearning for an evidence-based medicine society is an important concept. Similarly however, one could question how much the placebo effect 'interferes' with results and could potentially lead to errors in our judgement of what does and does not provide potentially efficacious results.

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