I was reading an interesting book the other day (Cracked: Why Psychiatry is Doing More Harm Than Good, by James Davies) about modern 'medical' (or drug) psychiatry. In it he mentioned an interesting quirk about side-effects and the placebo response that I hadn't been aware of.
He was writing about how - in the case of anti-depressants - there is only a small additional benefit over and above placebo conferred by taking the drug. In fact, this small additional benefit is typically only a few points on the 51 point Hamilton Scale (a standard before and after test often used in trials in this area). So the larger proportion of the total benefit is indeed the placebo effect.
But then he went on to mention how some of that additional benefit that the drugs have relative to placebo might be a quirk of the side-effects of the drugs.
It goes like this. All enrolled in the trial are told they might be on the active drug, or might be on a placebo. They have to be told of likely side-effects from taking the drug. In other words, they might get side-effects, IF they are allocated to the active drug.
Now, if someone is allocated to the drug (but does not know) then IF they get a side-effect, they then might well think "Hang on! That must mean I'm on the active drug?". Knowing this might well generate an incremental placebo benefit compared to not knowing.
Now, of course, some people NOT on the active drug might develop side-effects similar to the drug side-effects (either for independent reasons such as getting a dry mouth if they have a cold, or as an active placebo - actually nocebo - type response itself).
But it is reasonable to assume that this latter effect will be smaller than the former, and the difference between the two will presumably be greater the stronger and more diverse the side-effects of the active drug!
So some of the headline additional benefit (already rather small) marketed by big pharma may be somewhat illusory.
I wonder whether we bump into this with patients? "You might develop a reaction to treatment if we have done the right thing today and got those stiff segments moving...". Or some such.
But like I said, the placebo sure is slippery.