Every day, many of us take clinically proven drugs that fail to work as plannedor that trigger unexplained side-effects.

The reasons for this can be chemically complex, but new research suggests that there may also be a far simpler explanation: we think that they are having a bad effect.

It is called the nocebo effect, and it’s the dark side of the well-known placebo effect, when a patient’s health improves because he or she believes that a treatment is going to make them better. The nocebo effect can worsen symptoms, exacerbate side-effects and can render drugs less effective. In other words, expectation of sickness begets sickness.

There are a lot of pessimistic patients: one report suggests that more than a quarter of us may experience the nocebo effect when we take a drug. Researchers from the Cardarelli Hospital, Naples, say in the Journal of Investigational Allergology and Clinical Immunology: “Our data, collected in a large population, confirm that the nocebo effect occurs frequently in clinical practice.”

UK doctors agree. “We think that it is a relatively common phenomenon,” says David Blake, Professor of Joint and Bone Medicine at the Royal National Hospital for Rheumatic Diseases, Bath, who has written on the subject.

The positive power of the placebo effect has long been known. According to a report from the University of Mississippi School of Medicine, a study of clinical trials for antidepressants indicates that 40 per cent of people taking the active drug usually feel better, but so do 31 per cent of those taking a dummy pill.

Much less is known about the nocebo effect, and there may even be a biological trigger contributing to it. A paper from Turin University Medical School, in the current issue of Neuro-science, implicates the compound cholecystokinin (CCK), which is involved in pain signalling.

Negative verbal suggestions might trigger anxiety about an impending increase in pain. This raised anxiety activates CCK which, in turn, steps up the pain signals.

There is no doubt that emotions play a significant role, too. Dr Brian Olshansky, who reported earlier this year on nocebo in the Journal of the American College of Cardiology, says that patients who are anxious or depressed are more prone to suffer. So, too, are patients who are specifically asked if they are suffering adverse effects, which can send nocebo spiralling as high as 71 per cent.

This power of suggestion means that nocebo can often be triggered by poor bedside manners, says Dr Olshansky, of the University of Iowa Hospital. “A cold, uncaring, disinterested and emotionless doctor will encourage a nocebo response,” he says. “In contrast, a caring, empathetic physician fosters trust, strengthens beneficent patient expectations and elicits a strong placebo response. A compassionate, hands-on approach may be more valuable than any single medical therapy.’’ In one extreme case, Dr Herbert Spiegel, of Columbia University, believes that it may have had a hand in a patient’s death. Writing in the report Nocebo: The Power of Suggestibility, he reports a case at a large American Roman Catholic hospital, where doctors called for a priest to administer last rites. By mistake, the priest went to the wrong bed and so the wrong patient.

“He gave this patient last rites with an impressive air of authority and a brusque voice,” says Dr Spiegel. Within 15 minutes, that patient was dead, while the other lived for a few more days. Here are other examples of the nocebo effect.

Drug side-effects

Thousands of people suffer side-effects from prescribed drugs. In many cases they have traceable clinical causes, but it is now recognised that the nocebo effect may be at work in a significant number of cases.

Chest specialists at Cardarelli Hospital carried out investigations on 600 patients with a history of adverse reactions to various drugs. They found that a quarter had reactions to a fake, inactive compound. Patients were exposed to either an inert compound or an active drug, and the researchers found a nocebo effect for the dummy drug in 27 per cent of cases. Symptoms included itching and headaches, and the incidence was higher among women than men.

Impotence

The drug finasteride is known to be highly effective for the treatment of benign prostate disease, but one of the problems is that it is associated with erectile dysfunction or impotence. Doctors at the University of Florence believed that the relatively high rates of sexual dysfunction being found could not be explained by the chemistry of the drug and set out to see whether the nocebo effect was at work.

They divided a group of men with prostate disease into two sets. Both were told that they were being given a drug with proven effectiveness in the treatment of benign prostate disease. The second group was given the added information that it may cause erectile dysfunction, decreased libido, and problems of ejaculation.

Months later when a test for side-effects was carried out, those who had been given the extra information were more than twice as likely to have problems – 31 per cent of them had symptoms of impotence, compared with 9.6 per cent of the group not given the additional information. Similar differences were found for loss of libido and ejaculation.

“The burden of this nocebo effect has to be taken into account when managing finasteride sexual side-effects,’’ they say.

Health scares

Over the past decade there have been a number of health scares about electro-magnetic fields, including power lines and mobile phones. Researchers at the Nederlands Interdisciplinair Demografisch Instituut say that – although a number of studies have shown no links with ill-health – there are constant calls for new research that can, in themselves, be damaging.

“The nocebo hypothesis states that expectations of sickness cause sickness in the expectant individual. Maintaining anxiety by fostering doubts in gullible populations about the quality of the environment they live in may cause serious mental illness. Anxiety caused by health scares is an increasing public health problem,’’ they say.

Parkinson’s disease

Brain stimulation is an important and effective treatment in the fight against Parkinson’s disease.

In the procedure, electrodes are implanted in the brain to tackle some of the symptoms of the disease, which include tremor, muscle rigidity and Bradykinesia, an abnormal slowness of movement.

In one of the experiments, the stimulator was kept on but the patients were told that it had been turned off. Results show that although the stimulator was on, the patients said that they found it harder to move. ``This nocebo could be prevented completely by verbal suggestions of good motor performance,’’ say the researchers.

Mind over matter

A 2004 study suggested that one patient in six seen by a GP may have some form of psychosomatic illness, when physical symptoms such as stomach pains, headaches or fatigue have no medical reason and are caused by mental factors, such as anxiety and depression.

Some diseases are thought to be particularly prone to mental factors. These include psoriasis, eczema, stomach ulcers and irritable bowel syndrome.

Secrets may make us ill. A Dutch study, published earlier this year, said that the mental burden of carrying a secret may make someone physically unwell.

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