An advisory committee for the US Food and Drug Administration recently concluded that a popular over-the-counter oral decongestant (containing the ingredient phenylephrine) was no better than a placebo – the news spurring anger over how long ineffective medicines have been for sale.
But amid the criticism, writes Professor Ted Kaptchuk in The New York Times, there were also some who lamented the possibility that their favourite cold medicine would be taken from them. In their view, it may not work, but it still does something for them.
He writes:
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 the drug even provides placebo benefits.
In clinical trials reviewed by the FDA committee, phenylephrine and a placebo 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 colds simply resolved by themselves.
This controversy highlights the perplexing messages that imprison placebos in general. In research settings, placebo responses are powerful but a nuisance, as they make 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 shadows and become a legitimate component of health care? My research suggests so.
Placebo effects are health improvements initiated from the rituals, symbols and behaviours involved with healing. A 2020 review I co-wrote in the medical journal The BMJ examined data from more than 140 000 patients with various chronic pain conditions.
We found that placebo responses range from moderate to large and can account for 50% to 75% 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 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 work only 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 when patients know 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 with patients who didn’t receive 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 randomised 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 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 in which 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 sensitisation – when the nervous system over-emphasises or amplifies perceptions of discomfort.
This mostly involves non-conscious brain processes that scientists call Bayesian brain, which describes how the brain modulates symptoms. The intensification and the relief of symptoms use 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 $250bn 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 scepticism 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 tumours or cure infections.
Crucially, much discussion and reflection is needed among physicians and our healthcare 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 a placebo, should be ethical and have measurable benefits if it is to be used. But healthcare 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 and has been a leading figure in placebo studies for more than 30 years.
The BMJ article – Placebos in Chronic Pain (Open access)
The New York Times article – No better than a placebo (Restricted access)
See more from MedicalBrief archives:
The decades-long struggle to get ineffective decongestant off the shelves
Decongestants in cold medicines ‘ineffective’: FDA
Even disclosed placebos help cancer patients with fatigue