Placebos work even when patients know what they are

Lying to patients is almost always unethical. But, in order for placebos to work, we have to believe they are “real” treatments, which means the doctor would have to lie to us and say that the placebo was actually a real treatment. Or, in the case of a clinical trial, that it might be a real treatment. After all, if a doctor handed you a pill and said, “this is just a sugar pill”, you’d probably assume it wouldn’t work. But sometimes our assumptions are mistaken.

I led a team that recently conducted a systematic review – considered to offer the highest quality evidence – containing data from five trials of open-label placebos (placebos that patients know are placebos). We found that open-label placebos seem to benefit patients with back pain, depression, allergic rhinitis, irritable bowel syndrome (IBS) and attention deficit hyperactivity disorder (ADHD).

The history of open-label placebos can be traced back to at least 1965 when Baltimore doctors, Lee Park and Uno Covi, gave open placebos to 15 neurotic patients. They told the patients: “Many people with your kind of condition have been helped by what are sometimes called sugar pills and we feel that a so-called sugar pill may help you too.” Many of the patients got better. Paradoxically, since these were neurotic patients, they thought that the doctors had lied to them and given them real drugs.

Since Park and Covi’s pioneering study, many more rigorous ones have been undertaken. In a typical recent study that was included in our review, Ted Kaptchuk of Harvard Medical School randomly allocated 80 patients with severe IBS to receive either placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no treatment (the control group). After three weeks, the researchers found that the open-label placebo group improved by 15% more than those in the control group.

One of the participants in the trial, Linda Buannono, had been suffering from IBS for years and nothing had helped. On some days she was in so much pain she could barely leave the house. The open-label placebo had a big effect on her, so much so that she said: “I never felt better in my life.” But, at the end of the trial, she stopped receiving the placebos and her IBS became worse again. She went to her pharmacist to ask for some open-label placebos, but he told her it would be unethical for him to do so.

The trials in our systematic review were all quite small and weren’t “blinded”. (Blinding is where the participants and/or the researchers don’t know who’s getting what.) In these types of trials, participants and researchers need to know who is getting the open-label placebo and who isn’t, so it’s not possible to blind them. Trials that are not blinded are considered to be somewhat biased. However, the trials were consistently positive and we also know a bit about how open-label placebos work, suggesting that bias cannot explain away these results.

Lifting the lid on open-label placebos

Open-label placebos probably work in two ways. The first is expectation. Open-label are usually given with a positive suggestion (the doctor will tell the patient the pill is just a placebo but adds that it “produces significant improvement for patients like you”. This positive suggestion creates a positive expectation, which can activate the reward mechanisms in the brain and help the body produce its own substances, such as painkilling endorphins.

The second is conditioning. Just as Pavlov’s dogs learned to associate the sound of a bell with food and began salivating whenever they heard the bell, most of us have been conditioned to expect a positive outcome when a trusted doctor gives a treatment. So even though we know a pill is a placebo, our bodies may react in a way that helps us heal. There have been several studies, including one in humans, showing that the immune system can be activated much in the same way that Pavlov’s dogs salivated at the mere sound of a bell.

Since open-label placebos work, does this mean doctors should start handing them out like Smarties? That may be unwise because it would support a pill-popping, overmedicalised culture. Fortunately, our review of open-label placebos demonstrates something more general: placebo effects are real for many common conditions. And we can benefit from placebo effects without actually using placebo pills. Doctors who give positive messages and take time to communicate with enhanced empathy to patients can have positive benefits whether or not they give pills. Far from being unethical, since placebo effects can benefit many patients it is probably unethical not to exploit them.

Jeremy Howick has received funding from the National Institute for Health Research (NIHR) and the Medical Research Council (MRC), both in the United Kingdom.