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What’s the Opposite of the Placebo Effect?

Kelsey Tyler

A few years ago, a friend of mine came down with a full-body rash. (I’ll spare you the details, but it was not pretty.) Thankfully, his doctor prescribed him a steroid and the rash went away quickly. But as my friend was describing the medication to his mother on the phone, she casually remarked, “Just be careful, that steroid can make you jittery and cause heart palpitations.”

Right then, my friend noticed that he was a little jittery. He could also feel his heart beating — palpitating? — in his chest. 

How did these side effects come on so suddenly, right after his mother mentioned them? Shifting into health-psychologist mode, I floated a theory: He’d fallen victim to the nocebo effect.

You might be familiar with the placebo effect, where someone experiences measurable health improvements in response to a sham medical treatment, such as sugar pills. For years, studies have shown how effective placebo treatments can be when people believe they’re taking real medication. But there are also newer studies in which people knowingly take placebos and still see health improvements. Why? One explanation, supported by my own psychology research, attributes the results to a belief in the power of placebos. Whether or not people know they’re just swallowing sugar pills, the expectation of healing triggers a cascade of changes in the body that produce real physiological benefits. Placebo treatments have been shown to reduce pain and anxiety, calm Parkinson’s tremors and improve Alzheimer’s symptoms. 

The nocebo effect is the placebo effect’s evil twin: People experience real side effects from a medication or other treatment because they have negative expectations about it. In some cases, simply being informed about the possibility of side effects is enough to trigger the nocebo effect. For example, in a study of men receiving prostate treatment, some but not all participants were told that erectile dysfunction was a possible side effect. Those who’d been informed were 28 percent more likely than their blissfully unaware counterparts to experience erectile dysfunction. 

We often think that health is purely biological: We take medication, and it either works or it doesn’t. It either causes side effects or it doesn’t. But the truth is far more complicated, and far more interesting. What we think, believe and expect influence our physiological reality. If you aren’t convinced, try an experiment: Think about something that scares you. If it’s snakes, imagine one slithering past your foot during a nature walk. If your fear is public speaking, imagine yourself giving an important presentation at work. You might notice that your heartbeat speeds up, or that your palms start sweating. Maybe you feel a little breathless. All of these are very real physical sensations, but they were created entirely by your mind.

Research is only beginning to unpack the mechanisms underlying the placebo and nocebo effects. But there’s evidence that nocebo effects can happen on a large scale. One study in New Zealand looked at news coverage of side effects that patients experienced after switching from a brand-name antidepressant to a generic version. Even though the two medications were biologically identical, using the same active ingredients, some patients reported serious side effects, including suicidal thoughts, nausea and headaches, in response to the generic drug only. 

In order to inform the public about risks associated with the drug, two major media outlets ran stories on its potential side effects. The coverage came with an unintended consequence: After the stories were published, the number of side effects reported by patients increased 600 percent. Notably, the reported side effects were the same ones mentioned in the news stories. Reports of the drug’s other potential side effects — which had been just as common before the stories came out — didn’t increase at all. The news stories, the study authors argued, triggered a widespread nocebo effect: Telling people that certain side effects were likely to happen increased their prevalence substantially.

It’s not that patients were lying, but rather that they developed side effects because they expected to. Anxiety often exacerbates nocebo symptoms. Research also indicates that the nocebo effect can occur when patients have previously experienced side effects from taking a medication, and then exhibit a conditioned response when they take it again.

The nocebo effect can also happen when people misattribute normal, everyday symptoms to a new medication. (A side effect is a negative sensation that occurs as a result of medication or treatment, whereas a symptom is any negative sensation.) Mild aches and pains, headaches, nausea and rashes that resolve quickly are all normal parts of being a human. In fact, one study found that about 90 percent of people experience at least one symptom per week, with the typical person experiencing about five. The most frequently reported symptoms are back pain, fatigue and headaches, which are also extremely common side effects of medication. It’s possible (and likely) that people often blame medications for symptoms they would have experienced anyway.

How can we protect ourselves against the nocebo effect? We shouldn’t ignore side effects or symptoms, especially when they might indicate something serious. And if we’re feeling sick — especially with something contagious, like COVID-19 — it’s useful to be cautious and check in with a doctor. But we also don’t want the nocebo effect to interfere with helpful, let alone necessary, medical treatment.

As it turns out, knowing about the nocebo effect is often the first step to battling it. The next time you take a medication and experience a minor side effect, you can ask yourself: Is this something I might have experienced anyway, or do I think it’s caused by the medication? Of course, it’s not always possible to pinpoint the cause of a symptom. If you’re not sure, consider reflecting: If you weren’t taking the medication, would this side effect be something you’d pay a lot of attention to, or something you’d brush off as normal? If it’s the latter, the medication may not be to blame.

If you have information about the number of people who experience side effects from a drug — say 3 percent, you can also engage in what’s known as reframing. Tell yourself that if 3 percent of people experience side effects, that means that 97 percent don’t. Research suggests that reframing these numbers and focusing on the vast majority of people who tolerate a drug well is one way to reduce nocebo effects.

You can also work with your healthcare provider to understand which side effects are minor and likely to improve on their own, and which ones require medical attention. When you know that a side effect is merely bothersome rather than dangerous, it might be easier to tolerate. Especially if you’re prone to anxiety about your health, as many people are, you and your doctor can create a plan to prepare for side effects should they appear. This might include telling your provider that you’d rather not be informed about minor side effects.

Or you can try to view minor side effects as a sign that the medication is active in your body. Emerging research conducted by myself and others suggests that interpreting minor side effects as a sign of a drug’s efficacy can help turn an unpleasant sensation into an encouraging signal.

Nocebo effects are far more common in medicine than most people realize, and there’s still a lot of research needed to understand the best strategies to combat them. But you can start by looking for nocebo effects in your own life and understanding the ways your mindset might be shaping your health. And the next time your mom or another family member starts listing side effects you haven’t had, you can remind yourself that before you heard about them, you felt perfectly fine.

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