“You may feel a sharp pinch, but it will all be over quickly.”
Before the COVID-19 jab was plunged into our arms, most of us probably heard words similar to these. After the anticipated pinch, the nurse or doctor likely told us something about possible vaccine side effects. For one of us, the nurse’s forewarning was rather specific: “Around 12 hours from now you may experience a pain in your arm or feel flu symptoms. But don’t worry,” the nurse aimed to reassure. “This can be easily managed by Tylenol.”
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Sure enough, like clockwork, 12 hours later, the symptoms manifested.
An estimated 30% of people who received the COVID-19 vaccine also reported nasty side effects. Making matters worse, like a nightmarish self-fulfilling prophecy, the very words used by clinicians might well have caused some of this harm. Of course, doctors and nurses do not deliberately set out to hurt patients—far from it. They want to ensure that patients are fully informed. However, as our research shows, their words might unintentionally ramp up the effects of a psychological phenomenon that operates under the radar. This phenomenon is called the “nocebo effect.”
Characterized as the “evil-twin” of the placebo effect, nocebo effects are harms that arise from negative expectations. While placebo effects are those beneficial outcomes that arise when we expect to feel better and, as a result, do, nocebo effects are what happen when we expect to feel worse.
Read More: The Placebo Effect Is Real, and Scientists May Be Able To Predict Who Responds
Today, we expect our doctors to give information to us straight. Gone are the days when doctors could wilfully withhold information from patients, even if they believed doing so would make patients feel better. Yet, the best-known phrase from medicine’s oldest creed, the Hippocratic Oath, is “First, do no harm.” Nocebo effects are one of medicine’s natural disruptors: they present a challenging scenario because, sometimes, information may be bad for our health. Balancing honesty against the risks of harm is no easy feat and is one area where medical ethicists, health researchers, patients, and clinicians need to put their heads together.
COVID-19 offered an unprecedented global experiment into the size and significance of this effect. In 2022, placebo researcher Julia Haas led a review of COVID vaccine clinical trial data and concluded that the nocebo phenomenon could account for as much as three quarters of the side effects associated with the jabs. The evidence for this startling finding comes by comparing side effects between patients allocated to the placebo shot versus those allocated to the real shot in the vaccine trials. Those receiving only a saline injection with no effect on the body still reported many unwanted side effects. It is possible that some of these effects might have been due to “symptom misattribution.” At any given time, some of us may experience low grade aches and pains, such as headaches, or fatigue, and knowledge that the vaccine causes these effects might draw our attention to symptoms we’re already experiencing. Alternatively, some negative symptoms might have been caused, or worsened, by nocebo effects.
Beyond COVID-19, a growing body of research shows that nocebo effects may be commonplace in medicine and that the verbal suggestions uttered by clinicians really do matter. In one experimental study in 2004, radiology professor Dr. Elvira Lang and her colleagues found that warning or even sympathizing with patients about painful or undesirable experiences following an intervention increased pain and anxiety. In another 2003 study of beta-blockers for cardiac disease and hypertension, telling patients that treatment side effects might include erectile dysfunction (ED) led to a doubling of patients reporting this problem compared with those not given information about ED risk.
In 2010, Dr. Dirk Varelmann, a specialist in anesthesia and pain management at Beth Israel Deaconess Medical Center in Boston, wanted to explore whether the way in which a local anesthetic injection was described to patients would influence pain. Varelmann led a study where one group was told, “You will feel a big bee sting; this is the worst part;” the other group was informed, “We are going to give you a local anesthetic that will numb the area, and you will be comfortable during the procedure.” Those who were told they would feel a sting—that is, the patients receiving a negative suggestion—reported significantly more pain after the injection even though both groups got the same anesthetic. Varelmann’s conclusion was that, “using gentler, more reassuring words” could improve patients’ experience during invasive medical procedures.
Studies like this expose the ethical dilemma that nocebo effects invite. Since April 2021, patients in the U.S. have had the right to read their online medical records. Access rights include test results, medication lists, and the very words written by clinicians. Patients appreciate this. Surveys in the U.S. and other countries where access has been rolled out reveal patients who read their electronic medical records feel more in control of their care, and report better understanding and recall about their treatment plans. People who poke their noses into their records also report better understanding of the side effects of the medications they are prescribed.
However, there is a catch. In a study one of us conducted in 2021, some enlightened patients said they worried more about their medications after reading their clinical records. And while the connection has only been hypothesized, we shouldn’t be surprised if the language doctors use in our records gives nocebo effects unfettered free reign. In fact, as many as half of all patients in the U.S. who are prescribed medications for chronic conditions fail to take their meds leading to an estimated 100,000 preventable deaths and $100 billion in costs every year. Side effects are one of the main reasons patients discontinue treatments. If we can solve the nocebo problem, we might do a better job of keeping more people on their medications and staying healthy.
Nocebo effects are relevant even beyond the doctor’s office. They invite challenging questions about how governments should frame public health information, and how advertisers ought to sell their drugs on TV. The free press is a pillar of democratic societies, but even here the nocebo phenomenon raises interesting novel concerns. If journalists reporting on health veer into sensationalism and scaremongering, and this literally causes readers harm, was their choice of words unethical?
This brings us back to coronavirus. An estimated 70% of the world’s population received at least one COVID-19 jab. But many skipped their second shot, some because of fears about the vaccine’s side effects. Perhaps not even the most ardent conspiracy theorist could have imagined that a humble mind-body effect might have played a role in the pandemic’s gloomy story. But they should think again.
Knowledge is power, but it’s as equally important to remember that words matter. Let us not delay the “nocebo” conversation any longer.