The Nocebo Effect: Are Your Beliefs Making You Sick?

Expect to feel better after swallowing a pill, getting an injection or receiving another medical treatment, and there's a good chance that you will -- even if what you're given is nothing more than a sugar pill, a saline injection or another sham treatment. It's called the placebo effect, and it's so common that researchers regularly incorporate placebos in their clinical trials to see how much of a treatment's therapeutic effect actually comes from the medication or intervention, rather than people's expectations that it will be beneficial.

Well, here's a surprise: The placebo has a sibling with a dark side called the nocebo effect ("I will harm" in Latin), and it's the power of negative expectations to bring about adverse outcomes. It's a self-fulfilling prophecy in which being exposed to inert substances or being informed of a pill or procedure's potential side effects can actually elicit negative symptoms. In other words, someone can experience adverse events related to a drug, a food or a treatment simply because he or she expects them to develop. "It illustrates the power of belief, suggestion and expectation in terms of what we experience in our bodies," says Dr. Arthur J. Barsky, a professor of psychiatry at Harvard Medical School who has studied somatic symptoms, placebo effects and nocebo effects.

Yet, despite how common the nocebo effect is, most people are unaware of its existence -- or how far-reaching it can be. In 2015 alone, the nocebo effect has been linked to study participants' intolerance for statin drugs, increased pain with changes in wound dressing and changes in cognitive performance when given placebo pills (that warned of sedative properties) or when exposed to sham magnetic fields. The nocebo effect also can play a role in the development of skin rashes, asthma attacks, gluten sensitivity or people's response to surgical procedures, notes Dr. Morton Tavel, a clinical professor emeritus of internal medicine at the Indiana University School of Medicine who has written about placebo and nocebo effects.

In a 2012 review of clinical trials on pharmacological treatments for neuropathic pain, researchers from Greece found that nocebo responses occurred in 52 percent of the trials and the rates were higher among women. Not surprisingly, nocebo responses are one of the most common reasons people drop out of clinical trials. In a 2012 study from Germany, nocebo effects accounted for 72 percent of the dropout rate in drug trials for fibromyalgia syndrome and diabetic peripheral neuropathy.

Yasmina Ykelenstam, 40, has experienced this firsthand. Years ago, she was prescribed oxytetracycline for an acne outbreak on her face; though she was convinced the antibiotics weren't going to help, she took them anyway. For a while it seemed "like the drugs were going to work but then the blemishes would come back much worse while I was still taking the antibiotics," recalls Ykelenstam, a nutrition blogger and author of The Anti-Cookbook who lives in New York and London. She also experienced nausea, migraines and other unpleasant symptoms while taking the drugs. In retrospect, she believes this was due to the nocebo effect because, she says, "I have noticed over the years that I am more likely to develop side effects if I read the medical insert advising of them."

Mind Over Medicine

Exactly how the nocebo effect happens is the $64,000 question, but naturally there are theories. "There's some evidence that everybody has a reservoir of symptoms that come and go -- headaches, back aches, fatigue -- and most of the time we dismiss them," Barsky explains. "When you've been led to expect those symptoms might have something to do with a medicine, you reattribute those symptoms to the medicine and the symptoms become more intrusive, noxious and distressing, particularly if you have misgivings about being on the medicine."

People who are prone to catastrophizing, neuroticism or anxiety may be more susceptible to the nocebo effect, experts say. And "if you tend to have lots of medically unexplained symptoms, you're more likely to have a nocebo response," Barsky adds. Similarly, if you have a history of unsuccessful treatments, you might become conditioned to expect more of the same.

Moreover, how information is presented when a patient is asked to give informed consent for a treatment can make someone susceptible to the nocebo effect. For one thing, a health care provider's communication style can change the patient's perception of pain. "With epidural injections, when softer words are used to describe the sensation, patients experience less pain," notes Dr. Luana Colloca, an associate professor at the University of Maryland School of Nursing and School of Medicine who has researched the nocebo effect.

On the other hand, using strong words to warn about possible adverse side effects can increase the chances of a nocebo effect. Colloca has seen patients who've experienced nausea or dizziness with a prescription medication after reading the list of possible adverse effects. "Before the drug is even metabolized in the body, they start to feel sick," Colloca says.

In a 2014 study of patient expectancy in antidepressant trials, Dr. Bret Rutherford, a professor of psychiatry at the Columbia University College of Physicians and Surgeons, and his colleagues gave participants fluoxetine for their depression. After 12 weeks, some patients were switched to a placebo and some were told they might be switched to a placebo. In the latter group, those who were told they might get a placebo but actually stayed on fluoxetine experienced a worsening of their depressive symptoms. In other words, "changes in the patients' expectancy mediated the effect" of the treatment they actually received, Rutherford says.

There's mounting evidence that pessimistic beliefs and expectations can trigger hormonal, immunological and neurological changes that contribute to the adverse symptoms. When it comes to pain, the nocebo effect "can trigger an increase in brain activity in the hippocampus [as seen on functional magnetic resonance imaging, fMRI], which is related to pain processing, and these neurobiological events trigger an increase in pain," Colloca explains. "When it comes to anxiety, negative expectations increase activity in the [brain's] amygdala, which contributes to our fear of pain." It's an unfortunate ripple effect because "when you have increased pain, you become more anxious, and when you're anxious, you experience more pain," Colloca adds.

So what, if anything, can you do to guard against the nocebo effect? Being aware of the possibility that your symptoms may follow your expectations may help protect you from adverse effects. Also, "remember that you weren't symptom-free in daily life before you went on the medicine," Barsky says.

When given a new medication, it's also wise to ask your doctor or pharmacist what you can expect in the way of symptoms, discomfort and side effects -- and the true likelihood of these occurring. Health care providers can also take steps to minimize the chances of nocebo effects occurring. When presenting the 411 on possible adverse effects with a medication or treatment, "physicians and clinicians should frame information in a truthful way," Colloca says, "but balance the information so patients can understand how likely the risk is." After all, this may be an instance where TMI can harm you.

Stacey Colino is a freelance Health + Wellness reporter at U.S. News. You can connect with her on LinkedIn or email her at staceycolino@gmail.com.