The Nocebo Response

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“The biomedical view is so pervasive that we often fail to see it as such but view it as reality. Questioning this model is like asking whether a goldfish knows it is in water.” – O’Boyle, 1993

The placebo response has become a well-known, though severely misunderstood, phenomenon in popular culture. But many outside of the medical profession have never heard of the “nocebo response” which is often referred to as the “evil twin” of the placebo response.

A nocebo effect is an ill effect caused by the suggestion or belief that something is harmful. The term ‘nocebo’ became popular in the 1990s. Prior to that, both pleasant and harmful effects thought to be due to the power of suggestion were usually referred to as being due to the placebo effect.

But although the general public may not be aware of the term “nocebo response”, the concept behind it is certainly familiar. Many common phrases in our language (“scared to death”, “worried sick”) acknowledge the relationship between the mind and body and the power of thoughts and emotions to cause disease, and even death. In fact, the phenomenon of voodoo death – in which an adept in the voodoo tradition dies from fright after being hexed or cursed – is well-documented in the scientific literature.

The nocebo response is well-known to researchers. In placebo trials for disorders that produce minimal symptoms (e.g. hypertension), nocebo effects are comparable to those seen with an active drug. The most common adverse symptoms include headache in 7%, somnolence in 5%, weakness in 4% and nausea and dizziness in 1% each. In some studies, fatigue and gastrointestinal symptoms both occurred in almost 15% of subjects.

The mere suggestion that a drug can cause side effects can be a self-fulling prophecy for some patients. Studies have shown that the language adopted to describe side effects of drugs can significantly influence patient expectations and outcomes. (Barsky et al. 2002)

In the Framingham Heart Study, the largest and longest running study on heart disease in the world, women who believed they were prone to heart disease were nearly four times as likely to die as women with similar risk factors who didn’t hold such fatalistic views. (Voelker 1996)

A special report called “The Nocebo Effect: Placebo’s Evil Twin” published in The Washington Post in 2002 reported that in studies done of people going into surgery who want to die (to reconnect with a loved one), close to 100% of them die.

In a study of aspirin, patients were warned about possible gastrointestinal problems as a side effect at one location. At another location, no such warning was issued. Those who received the warning were almost three times as likely to experience the side effects. (Reid 2002)

In another experiment, asthmatic patients breathed in a vapor that researchers told them was a chemical irritant or allergen. Nearly half of the patients experienced breathing problems, with a dozen developing full-blown attacks. They were “treated” with a substance they believed to be a bronchodilating medicine, and recovered immediately. In actuality, both the “irritant” and the “medicine” were a nebulized saltwater solution. (Morse 1999)

In perhaps the most phenomenal study, Japanese researchers tested 57 high school boys for their sensitivity to allergens. The boys filled out questionnaires about past experiences with plants, including lacquer trees, which can cause itchy rashes much as poison oak and poison ivy do. Boys who reported having severe reactions to the poisonous trees were blindfolded. Researchers brushed one arm with leaves from a lacquer tree but told the boys they were chestnut tree leaves. The scientists stroked the other arm with chestnut tree leaves but said the foliage came from a lacquer tree. Within minutes the arm the boys believed to have been exposed to the poisonous tree began to react, turning red and developing a bumpy, itchy rash. In most cases the arm that had contact with the actual poison did not react. (Morse 1999)

So what is the significance of the “nocebo effect” in human health? The answer to that question depends on who you ask. The pharmaceutical companies’ primary interest in the nocebo effect is related to drug side effects, which cost the U.S. health system more than $76 billion a year (according to a 1995 University of Arizona study). If even a small percentage of those costs are caused by patient expectations of harm, addressing the nocebo effect could save drug companies a lot of money.

But for providers of health care not primarily motivated by profit, and for the average person, the nocebo response should be a powerful reminder of the capacity of our beliefs, expectations, thoughts and emotions to cause both health and disease. Many people of course know this instinctively. Yet in an era of medicine based increasingly upon technology and a specific type of scientific analysis, it is important to remember that the mind is not separate from the body, and that health and healing depend upon much more than doctors, hospitals, pills and diet.

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  1. Bruce says

    I read about the nocebo effect recently in a scientific paper reviewing all the popular low-carb diet books. Two examples were given of studies comparing low-fat to low-carb diets. All subjects met with a dietitian several times, who probably reinforced the low-fat diet (placebo effect) and discouraged the low carb dieters (nocebo effect). This variable needs to be controlled. All subjects should be given reinforcement or none of them should.

    http://www.scientificexploration.org/jse/articles/pdf/18.1_kauffman.pdf

  2. admin says

    Thanks for your comment, Bruce. I couldn’t agree more that trials need better controls for both the placebo and nocebo effect.

    Some have argued (rightly, I believe) that an inert placebo control isn’t enough, however, to guarantee a double-blind trial. Patients taking the active drug in a study often experience side effects, which of course leads them to suspect they are taking the drug and not the placebo and ruins the blind.

    A more accurate alternative would be an “active placebo”, which is a substance that does not address the disease in question but has some relatively benign physiological effects like producing dry mouth or stimulation (like a caffeine pill, perhaps). In studies done with active placebos, the difference between the efficacy of antidepressants and placebo was virtually nil.

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