A new study suggests that up to 76% of common side effects reported after a COVID-19 vaccine may be due to nocebo effects.
Earlier this month, a review study concluded that a significant number of adverse effects from COVID-19 vaccination can be attributed to nocebo effects.
A nocebo effect can be seen as the opposite of the placebo effect: for example, by increasing your pain experience just because you think something will hurt. More formally, the nocebo effect can be defined as a negative effect of a drug or placebo that is induced by patients’ expectations, and that is unrelated to the physiological action of the drug or treatment.
Placebos are an integral part of all clinical trials. They consist of an inert substance that is given to participants, and which is not expected to have any physiological effects. The goal is simple: to have a point of comparison against a drug being tested. In theory, when given randomly to a group of patients, those who received the placebo will experience no clinical effects, whereas those receiving a drug will experience some clinical effects.
But, placebos have been shown to have a clinical effect, both positive and negative. Many clinical trial participants, unknowingly receiving a placebo, report all sorts of benefits or side effects.
According to Dr Joe Kosterich, Perth based GP and Clinical Editor Medical Forum, these effects are very real.
“Both the placebo and nocebo effect are very real and demonstrate the power of the mind. Every clinical trial ever done shows some people on the placebo got benefit and some got side effects,” Dr Kosterich said.
About the study
The review study analysed data from 12 clinical trials, involving 45,380 participants and different types of vaccines, such as mRNA, viral vector, or protein-based COVID-19 vaccines.
The authors found that 76% of systemic adverse effects and 24.3% of local adverse effects could be attributed to nocebo responses from the participants after receiving the first vaccine dose. After the second jab, 51.8% of systemic adverse events and 16.2% of local adverse events were attributed to nocebo responses. According to the study, headache and fatigue were the most common adverse effects reported.
The findings of this study have potentially important implications, as a significant part of the population is afraid of vaccines, partly due to the purported side effects.
But, according to Dr Charlotte Blease, a healthcare researcher in General Medicine at Harvard Medical School, Boston USA, we should be cautious about these findings.
“The fact is, we can’t differentiate genuine nocebo negative effects from all of this other noise. Most of us walk around with some low-lying somatic symptoms anyway. So, some negative responses may have been an artefact of misattribution: asked whether you feel fatigued you might start to notice that you are. But this doesn’t mean it’s a nocebo effect. Rather, your heightened attention led you to notice,” Dr Blease told Medical Forum.
Further research is needed to disentangle the role nocebo effects have in vaccine side effects.
For Dr Blease, the bottom line is that we really don’t know if nocebo responses are actually causing any negative side effects, as opposed to someone paying more attention to what they are already feeling.
“So, if someone wants a vaccine but they also take seriously mind-body effects, including nocebo effects, they may wrongly infer that they are still at risk of nasty side effects even if those side effects are caused by their minds. We simply don’t know that to be true on the basis of these studies,” Dr Blease said.