Last month Wired, announced that Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

The article's a good read, and the basic story is true, at least in the case of psychiatric drugs. In clinical trials, people taking placebos do seem to get better more often now than in the past (paper). This is a big problem for Big Pharma, because it means that experimental new drugs often fail to perform better than placebo, i.e. they don't work. Wired have just noticed this, but it's been being discussed in the academic literature for several years.

Why is this? No-one knows. There have been many suggestions - maybe people "believe in" the benefits of drugs more nowadays, so the placebo effect is greater; maybe clinical trials are recruiting people with milder illnesses that respond better to placebo, or just get better on their own. But we really don't have any clear idea.

What if the confusion is because of the very concept of the "placebo"? Earlier this year, the BMJ ran a short opinion piece called It’s time to put the placebo out of our misery. Robin Nunn wants us to "stop thinking in terms of placebo...The placebo construct conceals more than it clarifies."

His central argument is an analogy. If we knew nothing about humour and observed a comedian telling jokes to an audience, we might decide there was a mysterious "audience effect" at work, and busy ourselves studying it...

Imagine that you are a visitor from another world. You observe a human audience for the first time. You notice a man making vocal sounds. He is watched by an audience. Suddenly they burst into smiles and laughter. Then they’re quiet. This cycle of quietness then laughter then quietness happens several times.

What is this strange audience effect? Not all of the man’s sounds generate an audience effect, and not every audience member reacts. You deem some members of the audience to be “audience responders,” those who are particularly influenced by the audience effect. What makes them react? A theory of the audience effect could be spun into an entire literature analogous to the literature on the placebo effect.

But what we should be doing is examining the details of jokes and of laughter -

And this is what we should be doing with the "placebo effect" as well -

We could learn more about what makes audiences laugh by returning to fundamentals. What is laughter? Why is “fart” funnier than “flatulence”? Why are some people just not funny no matter how many jokes they try?

Nunn's piece is a polemic and he seems to be conclude by calling for a "post-placebo era" in which there will be no more placebo-controlled trials (although it's not clear what he means by this). This is going too far. But his analogy with humour is an important one because it forces us to analyse the placebo in detail.

Suppose there is no such unicorn as a placebo. Then what? Just replace the thought of placebo with something more fundamental. For those who use placebo as treatment, ask what is going on. Are you using the trappings of expertise, the white coat and diploma? Are you making your patients believe because they believe in you?

"The placebo effect" has become a vague catch-all term for anything that seems to happen to people when you give them a sugar pill. Of course, lots of things could happen. They could feel better just because of the passage of time. Or they could realize that they're supposed to feel better and say they feel better, even if they don't.

The "true" placebo effect refers to improvement (or worsening) of symptoms driven purely by the psychological expectation of such. But even this is something of a catch-all term. Many things could drive this improvement. Suppose you give someone a placebo pill that you claim will make them more intelligent, and they believe it.

Believing themselves to be smarter, they start doing smart things like crosswords, math puzzles, reading hard books (or even reading Neuroskeptic), etc. But the placebo itself was just a nudge in the right direction. Anything which provided that nudge would also have worked - and the nudge itself can't take all the credit.

The strongest meaning of the "placebo effect" is a direct effect of belief upon symptoms. You give someone a sugar pill or injection, and they immediately feel less pain, or whatever. But even this effect encompasses two kinds of things. It's one thing if the original symptoms have a "real" medical cause, like a broken leg. But it's another thing if the original symptoms are themselves partially or wholly driven by psychological factors, i.e. if they are "psychosomatic".

If a placebo treats a "psychosomatic" disease, then that's not because the placebo has some mysterious, mind-over-matter "placebo effect". All the mystery, rather, lies with the psychosomatic disease. But this is a crucial distinction.

People seem more willing to accept the mind-over-matter powers of "the placebo" than they are to accept the existence of psychosomatic illness. As if only doctors with sugar pills possess the power of suggestion. If a simple pill can convince someone that they are cured, surely the modern world in all its complexity could convince people that they're ill.

[BPSDB]

Nunn, R. (2009). It's time to put the placebo out of our misery BMJ, 338 (apr20 2) DOI: 10.1136/bmj.b1568