The puzzle of the placebo effect

The placebo effect remains an ‘incontrovertible part’ of what clinicians see on a daily basis and medicine should seek to understand why, according to Dr Paddy Barrett

Be it immunotherapy, CRISPR gene editing or the Apple Watch ECG, there is little doubt we are firmly in the realm of a technology-based medical future. Thankfully, this medical future is largely evidence-based and founded on sound science: No witchcraft or snake-oil salesmen here. Or maybe that’s what we think, and a large part of what we still do today is influencing patient care in ways not too different from the faith healers of the past.

So what is the common thread that links today’s physicians with these historical healers?

The placebo effect.

Let me explain.

We have all encountered the patient who genuinely feels better after a simple conversation; no medications were prescribed, yet patient benefit was genuinely achieved. What is less obvious is the role of such an effect when the medical intervention was somewhat more substantial, as in the case of a reduction in knee pain after a sham arthroscopy procedure.

Now, I am not stating that all medical interventions, be they verbal, pharmacological or surgical, exert their influence solely via the placebo effect. But what is clear is that separating that effect from the medically-expected outcome is something as a community we continue to struggle with. So, if the placebo effect is an appreciable part of what we do as clinicians, are we very different to the ‘charlatan healers’ of the past?

Clearly, the answer is yes, and the reason lies in the evidence-based intent by which we approach each medical encounter. Yet the placebo effect remains an incontrovertible part of what we do on a daily basis, and we still don’t know how to appropriately factor it into clinical care or how to consider its role.

The word ‘placebo’ comes from the Latin ‘I shall please’, again a nod to our historical brethren who had little by way of genuine treatments to offer and simply gave their patients ‘something’ in an effort to please. And often it did.

Why it often ‘did please’ speaks in part as to the explanation of how the placebo effect might work. Reasoning as to why the placebo effect may exist includes concepts such as regression to the mean, an idea that implies that most phenomena have a natural fluctuation, so many of these occurrences are likely to improve anyway, irrespective of any preceding intervention.

Second is the expectancy effect, where when you think you are going to change, ie, improve, you do.

Clearly, there has to be a biological basis for these changes. Theories tend to focus on the release of endogenous cannabinoids or opioids, but in reality, our scientific understanding of the placebo effect is poor.

The placebo effect’s history is likely as old as ‘healing’ itself. One of the first official descriptions was by the Catholic Church, as far back as the 16th Century, in their testing of fake relics in the use of exorcisms on those they believed were feigning being possessed. They only used the ‘real relics’ for genuine cases of satanic possession. It wasn’t until around the time of World War II that the placebo effect was officially recognised and introduced into clinical trial testing. There have been countless studies investigating the role of placebo effect, ranging from its impact on mood, to chronic pain and the optimising of sports performance.

What is less studied, and even less recognised, is the role of the placebo effect’s ‘evil twin’, the ‘nocebo’ effect. Taking its name from the Latin ‘I shall harm’, the nocebo effect is when a placebo elicits a negative outcome, such as muscle aches in those on placebo statin therapies; or the withdrawal effects in those stopping placebo versions of hormone replacement therapy post-menopause.

The impact of both the placebo, and indeed nocebo effect, is that influence likely contaminates all our medical literature to date. Separating real from placebo-derived differences might be harder than we might wish to believe, particularly when our careers are so heavily invested in such interventions.

We have an easier time believing that a thoughtful encounter with an irritable bowel syndrome patient is likely to make a positive difference. But when it comes to the placebo effect’s role in more invasive procedures, we find ourselves proceeding with far more caution. Yet we know that the possibility is a genuine one.

It is estimated that 90 per cent of alternative medicines are placebo-based and, as evidenced-based physicians, we are comfortable accepting that figure. What makes us increasingly uncomfortable is the possibility that the role of the placebo effect is far more influential than we had previously considered when it comes to the medical interventions we provide, as evidence-based as they seem.

Will we ever entirely eliminate the placebo effect from medical practice?

I doubt it.

But what we can do is always consider its role, even when we are supremely confident of a medical intervention’s efficacy. Only then will we progress towards truth. And that is what will truly separate us from our faith healer cousins of the past.