Opinion | Placebo Effect is Powerful


An advisory committee for the Food and Drug Administration recently concluded that a popular oral decongestant sold over the counter was no better than placebo. The agency now faces the question of whether to pull medications that use the ingredient — called phenylephrine — off store shelves.

The news spurred shock and anger over how long ineffective medicines have been for sale. But amid the criticism, there were also some who lamented the possibility that their favorite cold medicine would be taken from them. In their view, it may not work — but it still does something for them.

I’m a researcher who studies the placebo effect, and in some situations, it’s powerful. That said, oral phenylephrine sold over the counter should be removed from the market; despite some people’s love of phenylephrine cold medicines, there’s no evidence that the drug even provides placebo benefits. In clinical trials reviewed by the F.D.A. committee, phenylephrine and a placebo each affected patients’ perceptions of nasal congestion equally — but the existing trials do not tell us to what extent people felt better because of placebo effects or because their cold simply resolved on its own.

This controversy highlights the perplexing messages that imprison placebos in general. In research settings, placebo responses are powerful but a nuisance, as it makes detecting a drug’s superiority over a placebo difficult. And in clinical practice they are powerful, but they often require deception, making them unethical. But can placebos ever come out of the dark shadows and become a legitimate component of health care? My research suggests so.

Placebo effects are health improvements initiated from the rituals, symbols and behaviors involved with healing. A 2020 review I co-wrote in the medical journal The BMJ examined data from over 140,000 patients with various chronic pain conditions. We found that placebo responses range from moderate to large and can account for 50-75 percent of the benefits of drug treatments for pain. Similar effects can be seen in research around symptoms such as cancer-related fatigue and menopausal hot flashes.

Fifteen years ago, in the middle of my career as a placebo researcher, I had a crisis. My ultimate research goal had been to harness the power of placebo to relieve unnecessary suffering. But my early experiments always involved telling participants that they might receive, or were receiving, real medications when they were not. Placebos were tainted by trickery. I began to question the conventional dogma that placebos only “work” if patients don’t know they’re placebos. Could I instead be honest? My colleagues thought I was nuts.

As it turns out, placebos can work even if a patient knows they are getting a placebo. In 2010, my colleagues and I published a provocative study showing that patients with irritable bowel syndrome who were treated with what we call “open-label placebos” — as in, we gave them dummy pills and told them so — reported more symptom relief compared to patients who didn’t receive any placebos. (These placebos were given with transparency and informed consent.) In another blow to the concept that concealment is required for placebo effects, my team recently published a study comparing open-label placebos and double-blind placebos in irritable bowel syndrome and found no significant difference between the two. A medical myth was overthrown.

Currently, more than a dozen randomized trials demonstrate that open-placebo treatment can reduce symptoms in many illnesses with primarily self-reported symptoms such as chronic low back pain, migraine, knee pain and more. These findings suggest that patients do not have to believe, expect or have faith in placebos pills to elicit placebo effects. So what’s happening?

To date, the best explanation for the results of open-placebo trials suggests that, for certain illnesses where the brain amplifies symptoms, engaging in a healing drama can nudge the brain to diminish the volume or “false alarm” of what’s called central sensitization — when the nervous system overemphasizes or amplifies perceptions of discomfort. This mostly involves nonconscious brain processes that scientists call “Bayesian brain,” which describes how the brain modulates symptoms up or down. Both the intensification and relief of symptoms share the same neural pathways. Considerable evidence also shows that placebos, even when patients know they are taking them, trigger the release of neurotransmitters like endorphins and cannabinoids and engage specific regions of the brain to offer relief. Basically, the body has an internal pharmacy that relieves symptoms.

What does this mean for medicine?

Physicians are unlikely to start prescribing placebo pills without much more rigorous evidence, which I would like to see as well, though I do think they could have a role. Especially for people who don’t receive relief from other therapies. At least $250 billion is spent yearly to care for symptoms like chronic pain that lack adequate or safe treatments, and the results are dismal. People treated in our open-label placebo trials usually express skepticism about what they are doing; it is often only their desperation that leads them to try.

But placebos shouldn’t be a first-line treatment — patients should be given what effective medicines are available. After all, placebos rarely, if ever, change the underlying pathology or objectively measured signs of disease. I like to remind people that they don’t shrink tumors or cure infections.

Crucially, much discussion and self-reflection is needed among physicians and our health care system as a whole to understand why the act of treatment itself is so powerful to patients even if a pill contains no therapeutic ingredients. Medicine is not only effective drugs and procedures; it’s a human drama of charged engagement. Our team published a study in The BMJ demonstrating that placebo effects can be significantly enhanced in the context of a supportive, respectful, and attentive patient-clinician relationship. Acts of human kindness in general are linked to robust placebo effects.

Any health intervention, whether it’s cold medicine or placebos, should be ethical and have measurable benefits if they are to be used. But health care should retain the knowledge that rituals, symbols, and human-kindness matter immensely when it comes to healing.

Ted Kaptchuk is a professor of medicine and professor of global health and social medicine at Harvard Medical School. He directs the Harvard-wide Program in Placebo Studies hosted at the Beth Israel Deaconess Medical Center. He has been a leading figure in placebo studies for over 30 years.

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