The placebo effect. Great expectations

Oct 30th 2008 | NEW YORK

From The Economist print edition

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Should doctors give patients placebos?

IN 1572 Michel de Montaigne, a French philosopher, observed that “there are men on whom the mere sight of medicine is operative”. Over the centuries, all manner of sugar pills and bitter tonics have been given to patients in the belief that they might do some good and probably will do no harm. The snag is that doctors have usually prescribed them without telling patients that the pills contain nothing proven to cure their disease.

While some consider this a virtuous lie, others argue it is unethical. The American Medical Association (AMA) even issued this stern warning in 2006: “Physicians may use [a] placebo for diagnosis or treatment only if the patient is informed of and agrees to its use.” That ruling was influenced by an article published by two Danish scientists, Asbjorn Hrobjartsson and Peter Gotzsche, in the New England Journal of Medicine. This concluded that “outside the setting of clinical trials, there is no justification for the use of placebos”.

To find out whether doctors are observing the AMA’s controversial ruling, a team led by Jon Tilburt of the Mayo Clinic, in Minnesota, conducted a survey of American doctors. The results have just been published in the British Medical Journal. Dr Tilburt and his colleagues canvassed a randomly selected group of 1,200 general practitioners and rheumatologists, the two groups of doctors who most often deal with conditions such as chronic pain that respond well to placebos.

Of the 679 physicians who replied, more than half said they prescribed “placebo treatments” from time to time and that they believed the practice ethical. Some 40% said they used painkillers or vitamins as placebos and 13% acknowledged using antibiotics and sedatives for this purpose. Barely 3% said they use sugar pills. Over two-thirds reported that they described the medicines to patients not as placebos, but euphemistically as “a potentially beneficial medicine or treatment not typically used for their condition”.

There are two explanations for the apparent popularity of placebos. One is that trials have shown that they work, and that the way they work is starting to be understood. Fabrizio Benedetti of the University of Turin’s Medical School, author of a new book on this topic*, points to a wave of studies using imaging to show which parts of the brain are involved in placebo responses.

His own research has even shown a placebo response at the level of single brain cells in patients suffering from Parkinson’s disease. He is convinced that scientists will soon be able to describe the “entire neuronal circuit which is affected by verbal placebo suggestions”.

Though the details remain murky, it is clear that the key to the placebo effect lies in the patient’s “positive expectation of a reward”, in the words of Nico Diederich, a neuroscientist at Centre Hospitalier de Luxembourg.

He observes that the use of placebos leads to the secretion of a chemical called dopamine in the brains of people with Parkinson’s disease (an illness characterised by the loss of dopamine-producing cells). Placebos also lead to the release of the body’s own opioid painkillers in those suffering from pain.

Both Dr Diederich and Dr Benedetti point to a technique called hidden dosing that demonstrates the power of the placebo effect. In one study that used this, post-operative patients were given morphine secretly, given morphine with fanfare or given a placebo that was falsely declared to be a powerful pain reliever.

This study, co-authored by Dr Benedetti and published in Nature, made the striking observation that telling a patient a painkiller is being injected into him, when the injection is actually a saline solution, is as potent as covertly giving him 6mg to 8mg of morphine. This is slightly below the standard post-operative dose of 10mg to 12mg, but the covert dose had to be increased to the full 12mg to surpass the effect of the placebo.

Great stuff, but there is a second reason why prescribing placebos may fall foul of the AMA: overworked doctors use them to deal with troublesome patients. In some cases this may still be legitimate. When a doctor suspects that a patient’s suffering is due to behavioural or psychological factors, rather than physiological ones, he may use a placebo as a diagnostic tool.

In other cases, though, the motives are less noble. A sympathetic doctor-patient relationship is believed to have a positive placebo effect in itself, but doctors do not get paid for holding your hand, notes Dr Tilburt. However, he observes, a placebo can sometimes be a good way of getting a whingeing patient out of the door quickly.

In the end, the controversy over the use of placebos is not likely to go away soon. Sceptics abound and ethicists frown, but doctors on the front-lines seem likely to continue to experiment with this potentially powerful tool while they wait for science to explain why it works.

And perhaps they should, given the role that positive expectations and the doctor-patient relationship plays in healing. That may be why, Dr Diederich observes, “even the ‘real stuff’ also produces some placebo effect”.

* “Placebo Effects”, Oxford University Press, October 2008

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