The placebo effect is a universally acknowledged phenomenon. In essence, if you think something is going to make you better, it probably will. If you believe that three tablets will do you more good than two, this may prove to be the case; if you believe that capsules are more effective than tablets, this may become your experience; and if you believe that expensive branded medicine must be better than the cheaper generic; this may turn out to be money well spent.

By contrast, the placebo’s darker cousin, the nocebo, is much less well researched and is rarely considered in clinical practice. The term nocebo is taken from Latin for “I will harm”^* and was first formalized in the 1960s to mean something that rationally should have no effect but actually causes a deterioration in health. The difficulty in researching the nocebo effect arises because ethics review committees tend to take a dim view of trials in which an intervention is likely to cause actual harm to the subjects.

There are many anecdotal examples of the nocebo effect at work. For example, a nocebo response may explain the phenomenon of the voodoo curse in which a victim dies only because a belief in the power of the witch doctor has been so ingrained that, after he has been hexed, the target simply cannot believe that he will live. Other cases have been reported in which a patient has died after having been given a terminal prognosis; only for a post-mortem to reveal no such fatal disease was present. A few scientific studies have also looked at the phenomenon, including one in which volunteers were told that the researchers were looking for a link between mobile phone usage and the incidence of headaches. Throughout the trial a number of users reported headaches, even when (unbeknown to them), the phone they were using was actually an empty shell.

Patients taking pharmaceutical drugs often report unwanted and nonspecific adverse effects that cannot be attributed to the pharmacological action of the medicine. In a review of studies examining the reported side effects from pharmacological treatments, several factors were found to be associated with an increase in the number of such reports, including the patient’s expectations of adverse effects at the outset of treatment; a patient’s prior experience with certain treatments; and particular psychological characteristics such as anxiety and depression.

Although poorly understood, physiological explanations of the nocebo effect have been proposed. It has been shown, for example, that a patient’s anticipation of worsening pain causes an increase in anxiety which triggers the activation of cholecystokinin that, in turn, facilitates pain transmission. This response generates a vicious circle of anxiety and pain which may be one explanation of the nocebo effect.

The nocebo effect has important implications for clinical practice, and there are several measures that physicians and other practitioners can adopt to limit its damaging effects. Health care professionals should try to identify in advance those patients most at risk of the nocebo effect, they should choose their language carefully in consultations with patients, so as not to generate any self-defeating attitude in the patient, and they should always consider that nonspecific side effects of drug treatments may be due to the nocebo effect, and manage accordingly.

Placebo and nocebo are two sides of the same coin. A strong relationship and effective dialogue between doctor and patient can take advantage of any placebo response while mitigating any response from its darker and opposite number, the nocebo effect.

^*The term placebo, meaning “I will please,” dates back to the 18th century.

References

Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific medication side effects and the nocebo phenomenon. JAMA. 2002;287:622-7. DOI: 10.1001/jama.287.5.622

Colloca L, & Benedetti F (2007). Nocebo hyperalgesia: how anxiety is turned into pain Curr Opin Anaesthesiol, 20, 435-439 DOI: 10.1097/ACO.0b013e3282b972fb

Oftedal G, Straume A, Johnsson A, Stovner LJ. Mobile phone headache: a double blind, sham-controlled provocation study. Cephalalgia. 2007;27:447-55. DOI: 10.1111/j.1468-2982.2007.01336.x