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What is a Nocebo?

You likely know what a placebo is, but have you heard of nocebo effects?

“The nocebo effect is the opposite of the placebo effect. It describes a situation where a negative outcome occurs due to a belief that the intervention will cause harm. It is a sometimes forgotten phenomenon in the world of medicine safety. The term nocebo comes from the Latin ‘to harm’.”

The nocebo effect

It’s not obvious from the name, but a nocebo is simply the opposite of a placebo.

What is a Nocebo?

But why would you want to give someone a placebo that makes them feel worse?

Misinformation can help drive nocebo reactions.
Misinformation can help drive nocebo reactions.

You wouldn’t!

“The nocebo effect can be influenced by ‘media storms’. Widespread dissemination of concerns about an adverse reaction to a medicine leads to an increase in the number of reports of the adverse reaction.”

The nocebo effect

But if a lot of people are telling you that you are going to have an adverse reaction when you do or take something, the idea of a nocebo is that you will be more likely to actually have that negative reaction.

“This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs.”

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials

And that’s what we have seen in the clinical trials for the COVID vaccines.

“Twelve articles with AE reports for 45 380 participants (22 578 placebo recipients and 22 802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose.”

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis

The folks who got placebos – saline placebos, had a significant number of adverse reactions.

“Common nonspecific symptoms such as headache and fatigue, which the study’s findings showed to be particularly associated with nocebo, are listed among the most common AEs after COVID-19 vaccination in many information leaflets. There is evidence that this sort of information may increase nocebo mechanisms such as AE-related anxiety and expectations. Furthermore, the information might cause a misattribution of commonly experienced nonspecific symptoms (eg, headache or fatigue) as specific AEs due to vaccination, even if these symptoms might have occurred in the absence of receiving any treatment.”

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis

While this doesn’t mean that all adverse effects are nocebo responses, it is definitely something to think about the next time you give or get a vaccine.

“Highlighting the probability of not experiencing AEs might also be beneficial.”

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis

Also know that:

  • nocebo effects seem to be more common in those with a tendency toward somatization reactions (turning psychological distress into physical symptoms)
  • nocebo effects can be increased if you only talk about the negative aspects of vaccination – overlooking the benefits
  • misinformation about vaccines can likely increase nocebo effects
  • people who are already hesitant to get a vaccine may be more prone to nocebo effects

So to reduce nocebo responses, remember that vaccines (not just COVID vaccines) are safe, and typically cause few serious adverse effects.

“The nocebo effect can be minimised by reducing negative expectations and anxiety about treatment, and placing discussion about the likelihood of adverse effects into the context of treatment benefit”

The nocebo effect: what is it, why is it important and how can it be reduced?

And of course, vaccines are very necessary, as the alternative, if you are unvaccinated, means that you have left yourself, and those around you, at risk to get a life-threatening disease.

More on Placebos and Nocebos

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