The placebo effect is the well-known phenomenon of a person’s physical or mental health improving after taking treatment with no pharmacological therapeutic benefit—a sugar pill, or a syringe full of saline, for example.
While the exact biological, psychological and genetic underpinnings of the placebo effect are not well understood, some theories point to expectations as the primary cause and others argue that non-conscious factors embedded in the patient-physician relationship automatically turn down the volume of symptoms.
Sometimes placebo effects can also harm –the so-called “nocebo effect” occurs when a person experiences unpleasant side effects after taking treatment with no pharmacological effects.
That same sugar pill causes nausea, or that syringe full of saline results in fatigue.
In a new study from Beth Israel Deaconess Medical Center, researchers compared the rates of adverse events reported by participants who received the vaccines to the rates of adverse events reported by those who received a placebo injection containing no vaccine.
While the scientists found much more trial participants who received the vaccine reported adverse events, nearly a third of participants who received the placebo also reported at least one adverse event, with headache and fatigue being the most common.
The team analyzed data from 12 clinical trials of COVID-19 vaccines. The 12 trials included adverse effects reports from 22,578 placebo recipients and 22,802 vaccine recipients.
After the first injection, more than 35% of placebo recipients experienced systemic adverse events—symptoms affecting the entire body, such as fever—with headache and fatigue most common at 19.6% and 16.7%, respectively.
16% of placebo recipients reported at least one local event, such as pain at the site of injection, redness or swelling.
In comparison after the first injection, 46% of vaccine recipients experienced at least one systemic adverse event and two-thirds of them reported at least one local event.
While this group received a pharmacologically active treatment, at least some of their adverse events are attributable to the placebo—or in this case, nocebo—effect, as well given that many of these effects also occurred in the placebo group.
The analysis suggested that nocebo accounted for 76 percent of all adverse events in the vaccine group and nearly a quarter of all local effects reported.
After the second dose, adverse events among the placebo group dipped to 32% reporting any systemic events and 12% reporting any local effects.
In contrast, participants who received the vaccine reported more side effects, with 61% reporting systemic adverse events and 73%reporting local adverse events.
The researchers calculated that nocebo accounted for nearly 52% of the side effects reported after the second dose.
While the reason for this relative decline in nocebo effects cannot be confirmed, the researchers believe that the higher rate of adverse events in the vaccine group the first time may have led participants to anticipate more the second time.
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The study is published in Julia W. Haas, Ph.D. One author of the study is JAMA Network Open.
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