The rise of the placebo

Bart Braun

Placebos are steadily gaining a more favourable reputation. Although the "pleasing pill" was once science’s odd-man-out, it’s now "an incredibly important extension".

Reader information leaflet: this article could give the impression that placebos are important drugs. Well, they are, although mainly because they are a means for medical practice, and medicine does more than that. Doctors prefer to prescribe drugs that work better, even better, than a placebo. The placebo effect cannot cure cancer or grow amputated limbs back. A placebo is not the same as a medicine.

For years, placebos were defined as exactly everything a medicine is not. Its literal translation – "I shall please" – sounds like an accusation. Let’s say you want to study a substance of which you hope it will help combat a disease. You take a group of patients: you give half of them your substance and the other half a sugar pill, or inject a saline solution. Without the second group, your research is worthless, because, in almost all cases, both groups will get better.

You can only say that your substance actually has a pharmacological effect if the first group gets better more often than the second. Of course, the medical world is far more interested in those kinds of substances. Ever since the nineteenth century, when the doctors realised the importance of a scientific basis, the chances that a visit to a doctor might actually cure you has increased by leaps and bounds. Anyone with pneumonia will prefer antibiotics to a bloodletting.

But what about the second group and their fake medicine? Why would a sugar pill or comforting words work at all? More and more people are looking into this. "Until recently, the placebo effect was the odd-man-out, something people didn’t talk about", Andrea Evers, Professor of Health Psychology, explains. "In recent years, there’s been a huge turnaround. There’s more support for research and doctors agree that this kind of effect can have a considerable impact on their daily practice: ‘I already know that what I say when I prescribe antidepressants is important’, they’re saying now."

More new stuff: brain research is being used to understand exactly what happens when the "pleasing pill" does its thing and this is helping to explain why the effect of a placebo is weaker in some people with Alzheimer’s: those parts of the brain have been damaged. Moreover, more and more studies using real patients are being published instead of studies done with psychology students recruited from the university cafetaria and given a pain stimulus, with or without real pain killers.

In short, placebos work because you expect them to. Your body produces extra saliva when it expects to eat and, in the same way, it produces extra painkilling substances when it expects pain to be alleviated.

Just because the placebo effect is "all in the mind", it doesn’t mean to say that it is vague, elusive or not real. Everything is the mind. There is no clear line between body and mind: an illness always affects both and so does a medicine. And body and mind affect each other, as placebos are seen to do, sometimes very impressively. For instance, Italian neurologist Fabrizio Benedetti proved that sufferers of Parkinson’s disease who were given a saline solution not only experienced fewer detrimental effects of their illness, they also produced more dopamine, of which they had too little. In other words: something real is happening here, something we can measure.

American placebo researcher Ted Kaptchuk conducted an inspiring study on people who suffered from Irritable Bowel Syndrome. Before he started, he gave them a detailed explanation of the placebo he wanted to prescribe; he told them that the effectiveness of placebos had been proved in countless studies and that they sometimes even worked just as well as "real" drugs. Those patients made huge strides: a placebo works even when you know you’re taking a placebo.

Kaptchuk, Benedetti and other great names from "placebology" visited Leiden just last weekend to attend the first global conference on the subject, organised by Evers and her colleagues for the Society for Interdisciplinary Placebo Studies.

In another of Kaptchuk’s experiments, asthma sufferers were given an placebo inhaler. The inhalers did not work: the patients’ lung function did not improve. However, when asked, the patients said they felt less breathless – it made no difference, for how they felt, whether they were given a placebo or a drug.

"Medicine has always focused on drugs, but now there’s more interest in how to deal with an illness and everything that happens in the surgery – how a GP prescribes a drug, for instance", say Evers. "That is an incredibly important expansion of the field. There have been plenty of discoveries in labs, but how do we apply them to GPs’ clinical practice? How much can we now say reliably and recommend to use in practice?"

Patients must be told how placebo effects work and doctors must be trained to deal with the placebo effects and its dark counterpart, the nocebo. Because that exists too: if you have poor expectations of a drug, it increases the chances that those expectations will become a reality. "In a Dutch study on breast-cancer patients, some were given lots of information about the side-effects while the others received less information", Evers continues. "The first group reported far more side-effects than the others. How much more relevant for doctors can it get? It’s time to produce some clinical recommendations."

Coloured pills work better

Suggestion and expectation have a large impact on the treatment of symptoms, which is especially noticeable in placebo research. An Amsterdam meta-analysis dating from 2000, for instance, suggests that four placebo tablets a day have a better effect on duodenal ulcers.
Some physicians seem to evoke more placebo effects than others and there seem to be large differences between patients too. If you compare similar studies from different countries, you can see even more large differences: fake acid-reflux inhibitors worked much better for Germans than for Brazilians.
Blue and green pills have a more calming effect than white ones and it looks as if bright colours like yellow are better at alleviating symptoms of depression. A placebo with a well-known brand name relieves headaches more effectively than a nameless pill.
The placebo effect seems to be getting stronger, especially in the United States, and can be explained by the fact that studies are being conducted more thoroughly, but there are researchers who suspect that the abundance of advertisements for drugs – legal in America – have some effect.
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