Placebo: Mind over Matter in Modern Medicine. Dylan Evans

there was an improvement in some ‘objective’ measures, such as walking distance and drug consumption, but both of these effects could have been due simply to the reduction in pain that followed both the real and the sham operations. A person who feels less pain when exercising can do more before he feels like stopping, and will consume fewer pills; there is nothing mysterious about that. These early studies, then, lend support to the view that placebos can affect symptoms but are powerless to cure disease – they may make you feel better, but they don’t make you get better.

      More recent studies of treatments for angina reveal a similar pattern. The main surgical operation for angina today is the coronary-artery bypass graft, in which small sections of vein are removed from the leg and grafted onto the coronary arteries to allow the blood to bypass the blocked areas. This operation does improve survival in the rare cases when the blockage is very serious, but in the majority of less serious cases it has no effect on life expectancy. In fact, when dye is injected into the blood vessels of these patients with less severe cases of angina, it is often found that the new grafts soon become blocked themselves. Surprisingly, though, many of these patients still report a significant reduction in pain.¹¹ Is the placebo response, then, an entirely subjective phenomenon, as some have claimed?

      Beecher and other pioneers of placebo research argued otherwise, but their data was not conclusive. They claimed that patients given placebos showed objective changes, such as constricted pupils, but they could not prove that these changes were directly attributable to the placebo response because their studies did not include no-treatment control groups. The sceptic could always argue that such objective changes might have occurred anyway. One early study went some way to meeting this objection by using a patient as his own control.¹² A man with a hole in his stomach was tested for the level of gastric acid after being treated with a placebo, and the results were compared with his reactions at other times when no treatment was administered. The gastric acid level fell twice as often when a placebo was used as when no agent was administered. The sceptic could still object, however, since the sample size was so small: only one patient, and only twenty-six observations.

      Fortunately, more recent studies have produced much stronger evidence. The studies that looked at the effect of ultrasound on postoperative dental pain, for example, found that objective measures were also affected by the placebo response.¹³ Not only did those who received the fake ultrasound (while the machine was switched off) experience a reduction in pain, but in one of the studies trismus was also significantly reduced compared to the no-treatment control group. Trismus is an involuntary contraction of the jaw muscles which keeps the jaw tightly closed – and can be measured objectively. Furthermore, in both of the studies there was also a significant decrease in swelling in those receiving the fake ultrasound. Inflammation is even less of a ‘mental’ process than trismus. The placebo response is clearly not just a subjective affair.

      ULCERS

      The fact that trismus and inflammation can be affected by dummy treatments shows that the placebo response is not limited to subjective symptoms. Nevertheless, if these were the only objective signs that placebos could affect, it would be a hollow victory for the placebo response, falling far short of dramatic claims such as that cited at the beginning of this chapter. Inflammation and involuntary muscular spasms may well be objective signs of pathology, but they are not particularly dangerous problems. Is there any evidence that placebos can affect more serious conditions?

      There is. Daniel Moerman, a medical anthropologist at the University of Michigan, has provided persuasive evidence that placebos can cure ulcers. Moerman began by gathering the results of seventy-one controlled trials of drugs for treating stomach ulcers. As usual, these studies did not include no-treatment groups, and so no individual trial provided direct evidence of a placebo response. By examining the studies together, however, Moerman was able to detect a pattern that did suggest that the placebos were having a powerful effect. Ingeniously, he compared those studies in which patients took two placebos a day to those in which patients took four placebos a day. In the first group, 33 per cent were healed, while in the second, 38 per cent were healed.¹⁴ This might not seem like a big difference, but it is statistically significant, and it has been replicated in another, more rigorous meta-analysis.¹⁵

      Comparing two groups of patients taking different amounts of placebos is almost as good, scientifically speaking, as comparing a placebo group with a no-treatment group. The fact that those taking more placebos showed more improvement strongly suggests that the placebos were playing an active role in assisting recovery. Furthermore, the improvement was not just subjective. All the studies examined by Moerman checked whether the ulcers had really healed by using an endoscope to peer inside the patients’ stomachs.

      PLACEBOS AND MENTAL DISORDER

      What about mental disorders? Can placebos cure diseases of the mind as well as diseases of the body? Unfortunately, the available evidence is once again quite weak. Despite the oft-repeated claims in the medical literature about ‘well-documented’ placebo effects in anxiety and depression, there are no properly controlled studies showing that people with these conditions do better when given a placebo than when deprived of one. In the absence of such studies, we can still look for relevant evidence by sifting through other data and comparing one set of trials with another, but we should bear in mind that the conclusions we draw on this basis must always be treated with a degree of caution. Until someone comes along and does a proper study involving a no-treatment group, it would be wrong to say that the placebo response has been clearly demonstrated for anxiety and depression.

      Although there are a few controlled trials comparing placebos to no treatment with patients suffering from various anxiety disorders, these suffer from methodological flaws and do not provide very strong evidence. There are other kinds of evidence, however, which – while by no means conclusive – do provide some basis for suspecting that placebos can reduce anxiety. One study, for example, looked at the effect of tablet colour in the treatment of anxiety states.¹⁶ In 1970, a group of researchers based at the University of Newcastle upon Tyne signed up forty-eight patients who had been diagnosed as suffering from anxiety states, and divided them into three groups. All of the patients received a course of oxazepam, which is a cousin of diazepam (Valium), but the pills given to each group were dyed with a different colour – red, yellow and green. The colours were switched around after a week, and then switched once more for the third week, so that each group tried each colour. Anxiety levels were monitored both subjectively (by self-assessment forms) and objectively (by the doctors – who were unaware of which colour pill the patient was taking at any particular time).

      When the results came in, some interesting trends were apparent in the data. The colour of the tablets seemed to have a subtle influence on the effect of the medication. In particular, green tablets tended to be most effective in reducing anxiety, and yellow the least effective. Anxiety manifests itself in a number of ways, from psychological symptoms such as worry and irritability to bodily signs such as palpitations, and for all of these phenomena green tablets were superior to the red or yellow ones. The differences were small, though, and did not reach statistical significance, except in one case – phobic symptoms. Phobia is one of the most common manifestations of anxiety, and green tablets were twice as effective as red or yellow ones in reducing phobic symptoms – even though the tablets contained exactly the same drug.

      When the effect of a drug varies systematically according to colour of the tablet in which it is administered, it is a fair bet that the condition being treated is placebo-responsive. The only way that something as insubstantial as colour can affect a medical condition is by way of the patient’s mind. The 1970 study on tablet colour does therefore suggest that some anxiety disorders at least may be placebo-responsive. Interestingly, the same study also pointed to a possible placebo effect in depression. This is not particularly surprising in itself,