Nocebo: placebo's evil twin

We are likely all familiar with the idea of a placebo effect. This occurs when we experience a response to a perceived treatment when the treatment itself is biologically active.

I have written several times about the power of placebo, so common and beguiling that it is controlled against in the majority of clinical research for new medical treatments.

The term nocebo effect has been used for something described as the placebo’s evil twin.  

Although there isn’t a standardized definition for nocebo effect, it really is seen as the flip side of the placebo.

It is thought to occur when patients attribute negative reactions they experience to a treatment intervention — even when they are given an actual placebo (or inactive medicine).

Symptoms are often nondescript such as headache or fatigue and seem to occur most often among women, those with pessimistic temperaments, or those with negative attitudes about the treatment being offered.

A study published in 2015 in the Journal of Clinical Psychiatry by researchers at Deakin University in Australia suggests the nocebo effect is quite common and should be considered in the design of psychiatric clinical trials.

Prevalence rates for nocebo effect vary depending on the clinical setting and type of therapy examined.

In this study, researchers examined data from 2,400 subjects in clinical trials involving antidepressants and found the nocebo effect could be responsible for more than 60 percent of treatment-emergent adverse effects and almost five percent of those who stopped treatment.

These researchers say the nocebo effect can impact a study by causing distress and treatment non-compliance among subjects. It can also potentially lead to a study medication being prematurely withdrawn from the market.

This information raises questions about how to avoid the nocebo effect in both research and clinical settings.

While some say providing too much information to patients of possible side effects may contribute to increasing the nocebo effect, we must respect a patient’s right to informed consent and autonomy and avoid taking a paternalistic role.

Gone are the days when the healthcare professional is the only source of medical information.

Increasingly, I see the phenomenon of someone with negative pre-existing attitudes about taking medication who then goes home and searches online for information from others who have had negative experiences and then are intolerant to the medication prescribed.

This happens with each medication in turn and sometimes the side effects experienced are very atypical and very difficult to explain on a biological basis. Some such individuals become impossible to treat for this reason.

Like the placebo, it will likely be impossible to eliminate the nocebo response. Our best bet is to identify it and do our best to minimize it.


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About the Author

Paul Latimer has over 25 years experience in clinical practice, research, and administration.

After obtaining his medical degree from Queen's University in Kingston, Ontario, he did psychiatric training at Queen's, Oxford and Temple Universities. After his residency he did a doctorate in medical science at McMaster University where he was also a Medical Research Council of Canada Scholar.

Since 1983 he has been practicing psychiatry in Kelowna, BC, where he has held many administrative positions and conducted numerous clinical trials.

He has published many scientific papers and one book on the psychophysiology of the functional bowel disorders.

He is an avid photographer, skier and outdoorsman.

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The views expressed are strictly those of the author and not necessarily those of Castanet. Castanet does not warrant the contents.

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