Research published this week based on multiple studies conducted over the past several years concluded that placebos can be effective even when those taking them are aware that they’re being given inactive pills.
This was a surprising finding since most of us have been led to believe that placebos work because people think they’re being given active medication, suggesting that the “placebo effect” is dependent on an element of deception. Because of an ethical proscription against lying to patients in clinical practice, the use of placebos has therefore been historically limited to research although calls to integrate them into medical care as safer alternatives to medications are increasingly common.
With this week’s published research, the UK-based newspaper The Guardian ran an article with the headline, “I knew they were sugar pills but I felt fantastic’ – the rise of open-label placebos.” It told of a woman named Linda Buonanno who was enrolled in a clinical trial for the treatment of irritable bowel syndrome and despite being aware that she would be receiving an “inactive substance like a sugar pill” nonetheless felt better. “I know it’s crazy,” she said, “I felt fantastic… I was able to go out dancing and see my friends again.” When the study concluded, the article said, she was “unable to obtain further effective placebos and her symptoms returned.”
For those familiar with the science of placebos, this is something of a ridiculous statement, reflecting a widespread misunderstanding of placebos and how they might work.
In recent years, other research attempting to link placebo response to observable neurochemical changes in the body and brain has led to a flurry of media headlines touting the increasingly popular belief that placebos can “help people heal themselves.” And yet, a more accurate view of placebos is that “they” aren’t really working at all.
To understand the details of why this is so, we need to start by defining a placebo as an inactive or inert pill. Although placebos are often referred to as “sugar pills,” a sugar pill isn’t an inert substance – if it was, no one would ever buy Skittles or any other pill-sized candy for that matter. So, modern day placebos aren’t sugar pills – they’re pills that look like medications, but contain no actual ingredients, sugar or otherwise, that cause any physiologic effects in the human body.
Next, we have to discuss the traditional role of placebos in research where they have served as comparisons to active medications in “randomized controlled trials” (RCTs). By randomly assigning half the subjects in a study to active medication and the other half to placebo, researchers can be confident that any observed differences in outcome between the two groups are due to medication since all of the other conditions that might affect an outcome are on average the same. Research subjects are usually “blinded” to whether they’ve been given active medication or placebo, as are the investigators rating their treatment response (this is known as “double-blinding”).
The importance of blinding was discussed in a previous Psych Unseen blogpost called, “The Blind Leading the Blind: Medications, Gluten, & Violins,” but the basic idea is that blinding prevents a study subject’s expectations from influencing the outcome of the study. It’s well-known that the expectation of a treatment response can lead to the subjective perception of that response, whether positive (e.g. a subject feels better or reports a reduction in symptoms) or negative (e.g. side effects; the so-called “nocebo” response).
For placebos, this mechanism of action has been called the “expectancy hypothesis,” though psychologically speaking, it’s simply an illustration of the power of confirmation bias. Believe an effect will happen and you’ll tend to look for evidence that it did. When blinding is well-done in a study, this confirmation bias is distributed equally across both treatment conditions and therefore cancelled out, so that it can’t be used to explain any observed differences in outcome between comparison groups.
What most people writing about placebos in the media forget is that the responses reported by research subjects taking placebos aren’t only due to expectation effects or confirmation bias. In an RCT, both positive and negative outcomes may also be a result of all of the other things that are occurring during study enrollment. For example, research subjects participate in assessments consisting of many hours of weekly face time with research staff who take thorough histories and closely monitor how a subject is feeling over the course of the study. This often amounts to much more time and attention than a patient would spend with their usual clinician in routine care.
This explains why placebo response in conditions like depression can often be as high as 50% – having someone listen to you and watch over you closely can make people feel better. Therefore, while research subjects treated with placebos are receiving an inert pill, that’s not the same as saying that they’re receiving “no treatment” – far from it.
Beyond the therapeutic effects of contact with caring individuals, research subjects are usually are paid for their time – usually modestly, but sometimes more significantly. They also often want to please the researchers and in the case of those with treatment refractory conditions, can feel thankful to have been enrolled in a study. These factors can lead research subjects to want to report positive effects, claiming that they feel better when they don’t necessarily feel any different.
It’s just as important to keep in mind that the reported outcomes in clinical trials might have nothing to do with the experimental conditions at all. Again taking the example of depression, symptoms like mood or insomnia often ebb and flow in response to other things happening in one’s life or for no detectable reason at all. Likewise, side effects like headaches might occur from any of a number of reasons, independent of being in a research study or taking a medication or a placebo.