Beware the nocebo effect

Every pharmacist is familiar with the placebo effect, in which patients have positive experiences after taking a dummy pill. But not everyone will be familiar with the opposite phenomenon, the nocebo effect, in which patients experience adverse effects after taking a bogus medicinal product.

The word “placebo” means “I shall be acceptable or pleasing” in Latin, and has been used in medical terminology since the end of the 18th century. “Nocebo” means “I shall cause harm or be harmful” in Latin and has only been used comparatively recently. Coined by Walter Kennedy in 1961, the word has been in general use only since the 1990s.

Feeling pain after taking a placebo medicine is an example of a nocebo effect. In one study in which participants were told that a (non-existent) electric current had been passed through their heads, 70 per cent experienced headaches.

But all sorts of physiological reactions can be ascribed to the nocebo effect. For example, an inhalation of nothing but saline can produce an increase or a decrease in airways resistance depending on what patients have been told to expect. And women in the Framingham Heart Study who believed they were prone to heart disease were nearly four times more likely to die as women with similar risk factors who did not believe they were at risk.

A review of over 100 double blind trials rated the overall incidence of adverse effects in healthy volunteers during placebo administration at 19 per cent, with higher rates following repeated dosing and in the elderly. The most common adverse events were headache, drowsiness and asthenia.

And a history of adverse reactions increases the chance of future nocebo effects. In one study of patients with such a past history, 27 per cent developed adverse side effects after taking placebo, with a significantly higher occurrence in females.

Although the phenomenon is poorly understood, a number of factors have been linked to the nocebo effect, including the patient’s expectation of adverse effects at the onset of treatment and psychological characteristics such as anxiety, depression and the tendency to “somatise”: some patients learn to associate medicine taking with somatic symptoms.

The most extreme example of nocebo is “voodoo death”. In some parts of the world a “medicine man” apparently uses the phenomenon to cause death by fright. Herbert Spiegel, in an article in Preventative Medicine, describes a medical voodoo in which a man was wrongly given the last rites and died within 15 minutes.