• Posted January 18, 2022

Vaccine 'Nocebo': If You Expect Side Effects, They May Come

Before getting their first dose of a COVID vaccine, many Americans were nervous about how they would react to the shot, but new research shows that fears of side effects may actually make side effects more likely.

To investigate this so-called "nocebo" effect in people receiving COVID-19 vaccines, researchers analyzed data from 12 clinical trials of COVID-19 vaccines and compared rates of side effects in more than 22,000 participants who received the vaccines and more than 22,000 who received a placebo shot.

After the first shot, systemic side effects -- symptoms that affect the entire body, such as fever, headache and fatigue -- were reported by about 46% of vaccine recipients.

But more than 35% of people who got the placebo shot also experienced similar side effects, a team of Boston investigators found.

At least one local side effect -- such as pain at the injection site, redness or swelling -- was reported by 16% of placebo recipients and two-thirds of vaccine recipients.

The nocebo effect accounted for many of the side effects in the group that got the dummy shot and for 76% of all side effects in the vaccine group after the first shot, the researchers calculated.

After the second shot, systemic side effects were reported by 32% of those in the placebo group and 61% of those in the vaccine group, and local side effects were reported by 12% of those in the placebo group and 73% of those in the vaccine group.

The nocebo effect accounted for nearly 52% of the side effects reported after the second dose, according to the authors of the study published Jan. 18 in the journal JAMA Network Open.

"Adverse events after placebo treatment are common in randomized, controlled trials," noted study author Julia Haas, an investigator in the Program in Placebo Studies at Beth Israel Deaconess Medical Center in Boston.

"Collecting systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide, especially because concern about side effects is reported to be a reason for vaccine hesitancy," Haas said in a medical center news release.

"Nonspecific symptoms like headache and fatigue -- which we have shown to be particularly nocebo-sensitive -- are listed among the most common adverse reactions following COVID-19 vaccination in many information leaflets," said study senior author Ted Kaptchuk, director of the Program in Placebo Studies and the Therapeutic Encounter.

But giving people that kind of information might backfire, he added, causing them "to misattribute common daily background sensations as arising from the vaccine or cause anxiety and worry that make people hyper alert to bodily feelings about adverse events."

"Medicine is based on trust," Kaptchuk said. Letting the public know that the nocebo effect might play a role in any vaccine side effect "could help reduce worries about COVID-19 vaccination, which might decrease vaccination hesitancy," he believes.

More information

For more on COVID-19 vaccine side effects, see the U.S. Centers for Disease Control and Prevention.

SOURCE: Beth Israel Deaconess Medical Center, news release, Jan. 18, 2022