It’s time to put the placebo out of our misery

We need to stop thinking in terms of placebo. The construct of the placebo has shifted several times during its history, from the periphery to the mainstream of medicine, from the lie that heals to a confounding factor in experiments, and to powerful medicine.1 I hope we will see another shift as we look back without nostalgia on the placebo, just as we look back on Galenic medicine and its humours, which were once plausible and useful but whose time has passed. It’s facile, however, to cite historical change as evidence that the placebo construct is unstable. All sorts of concepts change over time. So let’s stick with what’s wrong with the current placebo era and what could be right about a post-placebo era.

Shapiro and Shapiro described placebo as the only treatment common to all societies and cultures.2 Apparently almost anything can be a placebo, and a wide variety of medical conditions respond to it. Bausell claims that all forms of complementary or alternative medicine are placebos, including those with a massive share of the medical marketplace, such as herbal medicine, chiropractic, homoeopathy, hypnosis, and acupuncture.3 Singh and Ernst essentially agree.4 Placebos are not even needed to generate placebo-like effects. Secretly injecting morphine, for instance, seems to be less effective than doing the same thing and telling the patient about it.5 When placebo, or any other construct, can be virtually anything, then it just may turn out to be virtually nothing.

Nobody who came and saw the placebo has conquered its definition. Shapiro tried repeatedly until the definition became as convoluted with caveats as legislation.2 Grünbaum retried.6 Brody replied.7 Gøtzsche tried but failed.8 This is more than a hint that something is fundamentally wrong. Definitions have failed because attempts to capture the notion of placebo are like attempts to graft more epicycles on an earth centred theory of the universe. No matter how accurate the attempts, the placebo, like the earth, is not at the centre of any meaningful construct. It’s time to stop greasing the rusty gears of old notions with placebo oil, time for a shift into something new.

It’s not enough, however, to tweak the placebo construct a little bit here and there with equally mysterious subconstructs such as characteristic factors or to paint it over with a fresh new label such as “remembered wellness,” “non-specific effects,” or “meaning effects.”6 9 10 11 Rebranding is not enough to rescue this tired product. Instead, it’s time to return to the fundamentals. One fundamental may be that nobody knows enough yet about what’s really happening. Mind and body remain deeply mysterious.

Every way of looking at the placebo construct invites criticism, because it doesn’t make sense. A placebo is something inert that has an effect. Or something effective that is inert. That doesn’t make sense of either the word inert or the word effective. Of course, this oversimplification invites attacks on the notions of inert and effect. Similarly, to declare that a placebo is something with non-specific effects seems strange. If you can’t specify the effects, then how do you know what they are? On the other hand, if you can specify the effects, then they’re specific effects. Placebos are often the controls against which drugs are measured in clinical trials. But there are no standard tests to determine that they are placebos. Although experimenters go to great lengths to eliminate bias in drug testing, there’s a loophole for placebos. Those who have a stake in the results may also be involved in determining the content of the so called placebos. “So called,” that is, because finding an inert substance is rather like finding the universal solvent or the immovable object. For instance, to the extent that sugar has some effects, sugar pills are not inert. The same is true of many other commonly used placebos. Golomb writes: “It is paradoxical that there is no standard of evidence to support the standard of evidence.”12 There is no need to list all the nonsensical and paradoxical aspects of placebo here. For present purposes they offer another strong hint that something is rotten in the state of placebo.

If something cannot be defined and does not make sense no matter how it is viewed, it’s time to ask if it’s really there at all. This is not just a matter of words: it’s about a whole world view. The placebo construct conceals more than it clarifies. Unfortunately, asking you not to think placebo is like asking you not to think zero. We have all been born into a world in which the notion of zero exists, so it’s extremely difficult to erase our world view and imagine a zeroless viewpoint. It’s hard to see what’s hidden behind what isn’t there. Placebo is like a strange kind of zero that refuses to conform to accepted axioms.

Here’s a thought experiment to zero out the nothingness of the placebo. 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. The notion of audience effect serves no purpose, and much of what passes between performer and audience is obscured by constructing an audience effect and related notions such as audience responders. 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? We might even admit our ignorance of the magic behind laughter. But let’s leave the analogy with an audience effect and leap into the post-audience effect, post-placebo world of honest ignorance and clear inquiry.

You may justifiably be reluctant to abandon a notion with such a long history and one that may have served you well. But 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? Questions such as these—and there are many more—may further be directed at more specific inquiries such as what trappings are important and what beliefs make the most difference. There’s also the option of admitting that we just don’t know what cures this patient or what makes an audience laugh.

In a post-placebo era, experiments will simply compare something with something else. That is, they will compare experimental conditions: one group gets these conditions and another group gets those conditions. The report of every methodologically acceptable experiment will describe the conditions that have been compared, so that anyone reading the report may try to replicate them. There will be no hiding behind the skirts of the emperor’s new placebo. We will know from the detailed descriptions what constitutes each thing that is compared. We will reject from consideration any trials that are insufficiently described. Eventually we will have standard descriptions for commonly compared things. Legislation will reflect those standards. We gain transparency, honesty, and clarity.

If we put the placebo construct out of our misery, the implications and opportunities are huge. We need new literature, new textbooks, new training, and new laws that expunge the notion of placebo and replace it with something more fundamental, or we admit that we just don’t know. Look clearly at the naked emperor and see the body beneath the nothing that covers it. Why wait?