were noticeable placebo effects. For some conditions such as anxiety the results were too variable to allow a simple interpretation. For all sorts of pain, however, there was clear positive evidence of a significant placebo effect. Headaches, postoperative pain and sore knees could all be relieved by a sugar pill. There was, then, some reason to suspect that, in pooling the results of studies involving so many different kinds of medical condition, the true profile of the placebo response was obscured.
The mismatch between the complexity of the data analysed by Hrobjartsson and Gotzsche and the stark simplicity of their conclusion is yet another reminder of the need for caution in getting to grips with the research on placebos. What promised to be the final, definitive word on placebos turned out to be a poor study, full of flaws and capped by an inaccurate summary. If we are to get a good idea of what placebos work for – if, indeed, they work for anything – it seems we must go back to square one again, and look at the evidence bit by bit. Only in this way, proceeding carefully, can we begin to build up a picture of what placebos can really do.
NATURAL BORN PAINKILLERS
‘To talk about placebos,’ writes the American gastroenterologist Howard Spiro, ‘is to talk in large part about pain.’5 Of all the claims made for the placebo response, those that emphasise its power to relieve pain are the most well-established. The pioneers of placebo research focused almost exclusively on the painkilling properties of placebos. Most of the studies conducted by Beecher, Lasagna and others in the late 1940s and early 1950s were marred, however, by their failure to include no-treatment groups. Typically, they would report that a certain number of patients experienced pain relief after being given a placebo, and conclude that this had been caused by the placebo. This conclusion cannot be trusted, since no attempt was made to measure the spontaneous improvement in patients who did not receive a placebo.
Fortunately, more recent studies of placebo analgesia have included no-treatment control groups in addition to the experimental group and the placebo group. In most of these studies, the no-treatment group has been found to do significantly worse than both the experimental and the placebo groups. We can be confident, then, that the pain reduction experienced by those given the placebo would not simply have happened anyway. Placebo analgesia is real.
In a particularly striking study, patients who had undergone tooth extraction were treated with ultrasound to reduce the postoperative pain.6 Unknown to both doctors and patients, the experimenters had fiddled with the machine, and half the patients never received the ultrasound. Since ultrasound consists of sound waves of very high frequency – so high, in fact, that they are inaudible to the human ear – there was no way for the doctors or the patients to tell whether or not the machine was emitting the sound waves; the test was truly double-blind. After their jaws were massaged with the ultrasound applicator, the patients were asked to indicate their level of pain on a line where one end was labelled ‘no pain’ and the other ‘unbearable pain’. Compared with the untreated control group, all those treated with the ultrasound machine reported a significant reduction in pain. Surprisingly, it didn’t seem to matter whether the machine had been switched on or not. Those who had been massaged with the machine while it was turned off showed the same level of pain reduction as those who had received the proper treatment. In fact, when the ultrasound machine was turned up high, it was actually reported as giving less pain relief than when it was switched off.
We cannot be absolutely sure, even with this model study, that the greater relief experienced by those receiving the fake ultrasound, compared to those receiving no treatment, was due entirely to the placebo effect. Before the switched-off ultrasound machine was applied to the patient’s jaw, a coupling cream was rubbed on the skin around it, and this may have reduced the postoperative swelling by itself. Another study examined this possibility by including a control group of patients who were instructed to apply the facial massage, including the cream, to themselves.7 No reduction in the pain or swelling occurred in this group. The reduction in swelling could not, therefore, have been due to either the massage or the cream. It must have been due to the placebo effect.
Another study to include a no-treatment group compared the placebo response with the powerful painkilling drug buprenorphine.8 Fifty-seven patients with lung cancer who had undergone the notoriously painful operation of thoracotomoy (surgical opening of the chest cavity) and lobectomy (removal of part of the lung) were given injections of buprenorphine at thirty-minute intervals until the pain was adequately reduced. The next day, when their pain had returned to a high level, some of the patients were injected with salt water, while the rest were given no treatment at all. Those who received the saline injection experienced a significant decrease in pain over the following hour, while the pain level of the no-treatment group actually increased during the same period. Once again, the body had been encouraged by a pharmacologically inert substance to suppress its own pain.
KINDS OF PAIN
To say that placebos can relieve pain is to make a very general claim. For the species of pain are as abundant as the flora and fauna in a tropical rainforest. Pain can be flickering, quivering, beating or pounding. It can be sharp and cutting or dull and throbbing. It can be caused by material objects such as stinging nettles and bullets, or by tension and worry. There are mild pains, annoying pains, and excruciating pains. And pain can strike anywhere in the body; there are headaches, stomachaches, swollen ankles, and backaches. It would be impressive indeed if placebos could affect all these different beasts.
Without doing separate tests for each different kind of pain, we cannot be absolutely sure that placebos can relieve them all. However, nobody has yet identified a kind of pain that is completely unresponsive to placebos, which does suggest that they work across the board. The pain of a headache is typically very different to that experienced in the aftermath of a dental operation or chest surgery, yet headaches too are placebo-responsive. In one experiment, two British psychologists recruited over eight hundred female volunteers to take part in a study of headache pills.9 They gave the volunteers, at random, identical packets of pills, and told them to take two tablets for any headache they had during the following two weeks – and to note down how much relief they obtained. Half the tablets were placebos.
This study did not include a no-treatment group, but it got round this problem in an ingenious way, by making half the packets identical in every way to those of a well-known painkiller, while the remaining packets were simply labelled ‘analgesic tablets’. This applied to both the placebo packets and the packets containing the active tablets, which were of the same well-known brand. There were, therefore, four groups in the study: two placebo groups (one of which was issued with the placebo tablets in a branded packet) and two nonplacebo groups (with the same division into branded and unbranded packets).
By comparing the pain relief from all four groups, the experimenters were able to calculate the effects of branding itself on the treatment of headaches. The result was clear: within each group (placebo and nonplacebo), those taking branded tablets got more relief than those taking unbranded pills – though the branding effect was not as powerful as the effect of the active ingredient. Since branding must clearly act via a psychological route, this study supports the idea that headaches are no exception to the general rule that placebos can affect all sorts of pain.
ALL IN THE MIND?
Placebos are good at reducing pain. But if this were all they were good for, the placebo response could perhaps be dismissed as a mere figment of the patient’s imagination. Western medicine distinguishes between symptoms, which are subjective feelings reported by the patient, and signs, which are objective
