US researchers show negative version of placebo effect behind many symptoms such as headaches and fatigue
More than two-thirds of the common side-effects people experience after a Covid jab can be attributed to a negative version of the placebo effect rather than the vaccine itself, researchers claim.
Scientists in the US examined data from 12 clinical trials of Covid vaccines and found that the “nocebo effect” accounted for about 76% of all common adverse reactions after the first dose and nearly 52% after the second dose.
The findings suggest that a substantial proportion of milder side-effects, such as headaches, short-term fatigue, and arm pain are not produced by the constituents of the vaccine, but by other factors thought to generate the nocebo response, including anxiety, expectation and misattributing various ailments to having had the jab.
In view of their results, the researchers argue that better public information about nocebo responses may improve Covid vaccine uptake by reducing the concerns that make some people hesitant.
“Telling patients that the intervention they are taking has side-effects that are similar to placebo treatments for the condition in randomised controlled trials actually reduces anxiety and makes patients take a moment to consider the side-effect,” said Ted Kaptchuk, professor of global health and social medicine at Harvard medical school, and a senior author on the study. “But we need more research.”
Kaptchuck and Dr Julia Haas at the Beth Israel Deaconess Medical Center in Boston analysed adverse events reported during a dozen clinical trials of Covid vaccines. In each trial, those in the placebo arm were given injections of inactive salt solution instead of vaccine. The study did not look at severe, rare side-effects such as blood clots or heart inflammation.
Writing in the journal Jama Network Open, the researchers describe how after the first injection more than 35% of those in the placebo groups experienced so-called “systemic” side-effects, such as headache and fatigue, with 16% reporting site-specific ailments including arm pain or redness or swelling at the injection site.
As expected, those who received a first shot of vaccine were more likely to experience side-effects. About 46% reported systemic symptoms and two-thirds experienced arm pain or other localised symptoms at the injection site.
When the researchers looked at side-effects after the second jab, they found the rate of headaches or other systemic symptoms was nearly twice as high in the vaccine group compared with the placebo group, at 61% and 32% respectively. The difference was even greater for local ailments, reaching 73% among those who had the vaccine and 12% in the placebo group.
Overall, the researchers calculate that about two-thirds of common side-effects reported in Covid vaccine trials are driven by the nocebo effect, in particular headaches and fatigue, which many Covid vaccine leaflets list as the most common adverse reactions after a shot.
While evidence suggests that information about side-effects can cause people to misattribute common ailments to the vaccine, or make people hyper-alert to how they are feeling, Kaptchuk argues for more information about side-effects, not less. “Most researchers argue that patients should be told less about side-effects to reduce their anxiety,” he said. “I think this is wrong. Honesty is the way to go.”