The COVID pandemic has highlighted several interesting features of modern medical practice – most recently the “nocebo” response, which can cause a significant number of side effects people experience after vaccination.
The Nocebo responses (from the Latin noci: to harm) are the opposite of the best known placebo. While the latter describes improvement in symptoms following an inert drug, the nocebo response intensifies symptoms if a person anticipates them. It can increase the pain if someone expects something to hurt them.
A fascinating meta-analysis reviewed data from 12 COVID vaccine clinical trials, involving more than 45,000 participants, and found that about two-thirds of common side effects people experience after vaccination may be due to a nocebo response, rather than a to the vaccine itself.
Nocebo’s responses can be awkward and meaningful. They include headaches, fatigue, muscle aches, nausea, or diarrhea. These symptoms may be related to anxiety or negative expectations, or everyday feelings wrongly attributed to treatment.
While previous analysis in other areas had already confirmed the presence of nocebo responses in randomized trials, COVID vaccine research dramatically highlights its frequency.
The latest study found that up to 35% of patients in the placebo group of vaccine trials experienced adverse effects such as headaches and fatigue. Mathematical analysis showed that 50-75% of patient symptoms after actual vaccination (not placebo) may have been caused by these nocebo responses.
Another group of Italian researchers looked at other COVID vaccine trials and confirmed these conclusions. These findings are potentially significant because hesitation and refusal of vaccination have been linked to patient concerns about side effects or major adverse events. Knowing how often self-limiting nocebo responses occur can reduce vaccine hesitancy.
The “Meaningful Response”
Together, the placebo and nocebo effects are best understood as two aspects of what doctors call a “meaningful response.” Both occur in relation to the importance and what patients place on their diseasetheir relationship with their healthcare providers, and their thoughts and beliefs about proposed treatments.
Nocebo responses are now recognized as potentially significant contributors to patient outcomes. For example, if a doctor or nurse gives pessimistic or negative information about pain, various studies have shown that the patient’s pain may worsenregardless of the degree of tissue damage.
Not feeling validated or respected by the doctor can also inhibit the effectiveness of drugs and increase side effects.
Previous research in New Zealand has also illustrated how negative media coverage can increase patients’ experience of adverse events following mandatory changes to their medication regimen. For example, thyroxine brand switches in 2007 and a antidepressant in 2018 were followed by an increase in reports of side effects and adverse events.
Recognizing and publicizing the potential contribution of nocebo responses can be helpful in generic substitutions.
Implications for COVID vaccinations
Vaccinators should avoid inadvertently contributing to nocebo responses when counseling their patients. They could use positive framing on the very low risk of serious adverse events. They could also briefly explain that nocebo responses are common and self-limiting.
However, my own experience as a patient receiving three COVID vaccines was disconcerting. No one in the various vaccination teams said anything positive about the vaccine or its effectiveness in preventing me or my family from catching the virus, or in reducing the severity of the disease if we did. .
And right after I got the third injection, I was even more worried about warnings about chest pain and reminders that I needed to see a doctor right away if I had any. This additional information about heart problems as a potential adverse event followed recent concerns about rare cases of myocarditis after vaccination.
All of the vaccination staff were conscientious and kind, but it seemed odd that they weren’t tasked with discussing the benefits of vaccination. This could have been a useful approach to tackling vaccine hesitancy nationwide.
Although well-intentioned, it is possible that a focus on serious vaccine side effects could increase the incidence of nocebo responses in a population already primed for them. This could mean that more patients will present to their doctors or emergency departments with symptoms unrelated to the vaccine itself.
How to improve awareness
For the record, the advice of vaccinators seems quite variable. It may be helpful for them to incorporate an understanding of potential placebo and nocebo responses into their vaccination advice to each patient.
Health authorities and healthcare professionals need to understand the meaning of the responses and their role in clinical practice. Incorporating this knowledge into health care communication can prevent unnecessary patient anxietyworrying symptoms and considerable health costs.
Respecting autonomy means patients should be asked if they wish to receive information about side effects or adverse events. It’s about how to inform patients of the very low risk of serious harm while not increasing their apprehension.
Pandemic research is now also exploring potential parallels between long COVID and other chronic diseases such as myalgic encephalitis/chronic fatigue syndrome as well as tentative associations between negative childhood experiences and vaccine hesitancy.
Without wishing to minimize the devastating impact of the pandemic, it provides us with useful information on broader current medical and sociological issues.