A third of participants in a placebo Covid-19 vaccine trial reported experiencing side effects such as fatigue, headaches, and local reactions like pain at the injection site, according to researchers at the Beth Israel Deaconess Medical Center (BIDMC) in Boston. The team analyzed 12 randomized, placebo-controlled studies with a total of approximately 45,000 participants, finding that systemic adverse drug reactions occurred more frequently in those who received the actual vaccine. However, around a third of those who received a placebo injection also reported experiencing vaccine reactions. After the first dose, over a third (35.2%) of the 22,578 placebo recipients reported adverse drug reactions, with headaches (19.3%) and fatigue (16.7%) being the most commonly reported. After the second dose, nocebo reactions occurred in just under a third (31.8%) of placebo recipients. Those who received the actual vaccine experienced side effects more frequently, with almost half (46.3%) reporting at least one adverse drug reaction.
The authors note that some of the unwanted events are attributable to the nocebo effect, even though the participants received a pharmacologically active treatment. The analysis shows that the nocebo effect was responsible for more than three-quarters (76%) of the adverse drug reactions in the vaccine group after the first dose. After the second dose, the nocebo effect was responsible for more than half (51.8%) of the adverse drug reactions. “Undesirable events after a placebo treatment are frequent in randomized, controlled studies,” says Haas. According to Haas, it is important to document such nocebo reactions in vaccine studies to dispel concerns about Covid-19 vaccine side effects. Ted J. Kaptchuk, a professor of medicine at Harvard Medical School and a researcher at BIDMC, explains that nonspecific symptoms such as headaches and fatigue are often mistakenly attributed to the vaccine, even though they are simply the result of everyday sensations.
The study’s findings suggest that the nocebo effect may play a significant role in vaccine side effects, and that it is important to distinguish between actual adverse drug reactions and those caused by the nocebo effect. The authors recommend that future vaccine studies include a placebo group to help identify and quantify the nocebo effect. By doing so, they hope to alleviate concerns about vaccine side effects and encourage more people to get vaccinated against Covid-19.
