Safety concerns about vaccines are among the most common reasons for vaccine hesitancy. Since mortality rates are negligible following COVID-19 vaccinations, this leaves the only significant physical concerns are the non-deadly negative side effects of vaccines, as discussed below.
The “placebo effect”is defined as any improvement of illnesses or reduction of subjective symptoms that result from interventions lacking known physical effects. By contrast, “the nocebo effect” refers to undesirable symptoms that follow interventions also lacking such physical effects, which may also explain many perceived detrimental responses to vaccinations.
Although not fully understood, the mechanism of both placebo and nocebo effects relate primarily to the power of the brain to affect bodily sensations and functions. Placebos are especially effective in relieving subjective symptoms of pain, anxiety, fatigue, insomnia, and depression, but can go beyond this to counter various physical ailments. The reverse side of this coin, the “nocebo” effect,refers to any discomfort or illness resulting from similar (inert) interventions, and they can be quite powerful.
THE “NOCEBO EFFECT”: A CAUSE OF ILLNESS OR DISCOMFORT
Nocebo effects often take the form of distressing symptoms such as headaches, gastrointestinal upsets, and many others. In published drug trials, rates of distressing symptoms among recipients of placebos vary, reaching as high as 70% or more of these subjects, and they represent, in reality, nocebo responses. To gain better insight, however, into the sole nature of nocebo effects, we must, if possible, explore this response free of complicating factors found in drug trials, because in these latter trials, study subjects are assumed to anticipate both improvements and/or side effects from the drugs under study. To minimize these potential complications, vaccine trials offer an advantage, since these study subjects have fewer prior reasons to expect positive or negative responses. From a recent review of twelve studies including reports for 45,380 trial participants undergoing vaccination against COVID-19, general adverse systemic (nocebo) reactions were experienced by approximately 35% of placebo recipients after both first and second doses. By contrast, similar adverse reactions were encountered in 46% of those receiving active vaccine after the first dose, rising to 61.4% after the second dose. This means that at least 35% of all adverse effects can be attributable to the nocebo effects alone. The main adverse systemic effects in both placebo and vaccine groups were headaches and fatigue, but also consisted of nausea, diarrhea, malaise, joint pain, and headache, with both groups (placebo and vaccine recipients) showing no difference in severity of these symptoms. Such data strongly supports the pure power of the Nocebo effect itself.
PRACTICAL IMPLICATIONS OF THESE FINDINGS
The inordinately high apparent rates of adverse events from COVID-19 vaccines result from a combination of the modest active vaccine and the superimposed high rate of adverse nocebo responses. Common symptoms, such as headache and fatigue, are listed among the most common adverse effects after COVID-19 and other vaccinations in many information leaflets, and such information may increase anxiety and negative expectations further prompting increased nocebo responses. This may explain why many members of the general public resist all vaccinations Full disclosure of these undesirable results combined with disclosures of rates and manifestations of nocebo responses may be helpful in overcoming these obstacles. Informed consent forms containing accurate information about nocebo effects and the probability of not experiencing such responses may help to alleviate anxiety and reduce side effects. To gain a better outcome, positive reinforcement by administrators of the likely benefits of all such procedures may serve to discourage the nocebo effect.
CONCLUSION
The success of most medical interventions depends, at least in part, upon superimposed positive (placebo) or negative (nocebo) effects, both of which are powerful and reflect influences originating in the brain. To effectively manage such problems, administrators must understand these influences and convey them to all vaccine recipients. Hopefully, this will minimize negative responses, which, in the process, may serve to reduce the general fear of all vaccinations and, in the process, enhance their acceptance rates.
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