Are you certain you've never had a placebo?

Imagine the following situation: after a few days struggling with an illness, you decide to visit your doctor. He listens calmly as you describe your symptoms, strokes his chin thoughtfully and then writes out a prescription. “Take two of these, morning and evening and you’ll be back in the pink in no time,” he says confidently. If you were later to discover that the pills were, in fact, sugar pills, you might be tempted to complain to the appropriate regulator, or at the very least to find a new doctor. But did the doctor actually lie to you, or did he simply recognise one of the most remarkable truths in medicine: that placebos can have remarkable curative properties?

The word placebo is derived from the Latin for “I shall please.” Various technical definitions have been proposed for the placebo effect, but broadly speaking, it is the improvement in a condition as a result of a medical intervention not produced by any direct physiological or pharmacological effect of the intervention. The placebo effect does not require a ‘fake’ drug: a patient who is given a genuine drug which is pharmacologically effective against a condition can have the drug’s effectiveness enhanced by the placebo effect. Nor does the intervention need to be in the form of a pill. Placebo injections, placebo radiation and even placebo surgery have all been found to be effective.

How, then, do placebos work? Obviously the human psyche is involved at some point, and it is perhaps not surprising that the conditions for which the placebo effect has been most pronounced are psychological disorders such as depression. Irving Kirsch and Guy Sapirstein of the University of Connecticut conducted a meta-analysis (a study of other studies, considered the gold standard of medical evidence) of 19 clinical trials in which a total of 2,318 patients had been randomly assigned to receive either antidepressant medication or a placebo. Their conclusion? 75% of the effectiveness of Selective Seratonin Reuptake Inhibitor’s - a group of medications commonly prescribed for anxiety and depression- is attributable to the placebo effect. The figure has been disputed, but not the fact that the a patient’s knowledge that he is being treated forms a considerable part of the effectiveness of antidepressants.

Ever since the publication in 1955 of a seminal paper, The Powerful Placebo, by Howard K. Beecher conventional wisdom has held that placebos can bring about objectively observable physical improvements in patients suffering from a wide range of ailments. For example, in a study of asthmatics, doctors found they could produce dilation of the airways using a pharmacologically inert “bronchiodilator”. A meta-analysis found that, not only did 52% of colitis patients report improvements when treated with placebo, but that 50% of the inflamed intestines actually looked better when examined with a sigmoidoscope. It is this ability of a placebo to produce physiological changes in the body, as opposed to simply making the patient feel better, that is usually termed the powerful placebo effect.

Various explanations have been advanced for how the powerful placebo effect might work against various conditions. It is accepted, for example, that adrenaline, the body’s “fight or flight” hormone, and other stress-induced hormones, are immunosuppressants – they inhibit the normal function of the immune system. Since a placebo may relax a patient, and reduce levels of immunosuppressant hormones, it is logical that it may speed recovery from infection. Similarly, asthma attacks can be stress-induced, and so a reduction in stress could explain the effect of a placebo bronchiodilator.

As a result of Beecher’s paper, the accepted standard for clinical trials has become the randomised, double blind, placebo controlled trial. (RCT)

The methodology of an RCT based trial starts with recruiting a group of patients, all suffering from the same condition. They are then assigned randomly – usually by using a computer - to either the clinical group (the group receiving the intervention) or to the placebo group. Neither the patient’s doctor nor the patient is allowed to know what group he or she is in (this is the “double blinding” process, and is intended to ensure that doctors do not subconsciously show more concern or optimism to patients receiving the ‘genuine’ treatment). The trial must be designed so that neither the medical staff nor the patients will notice any difference between the ‘genuine’ clinical treatment and the placebo treatment – they must be indistinguishable. As an example, both the clinical group and the placebo group may be given a pill; although one pill will be the test drug and the other the placebo; both pills will look exactly the same and they will be given to both groups at the same frequency and dosage. The drug is declared effective if and only if the clinical group perform significantly better than the placebo group. Medical ethics require that doctors do not lie to their patients, and so the consent form must explain all the above to the recruits.