The simple act of swallowing a pill, even if that pill contains no active ingredients, has the power to affect a patient’s symptoms – especially when it comes to depression and pain management. This is known as the placebo effect, and it’s the reason clinical trials must compare new treatments with ‘fake’ treatments in order to demonstrate that they actually work. There’s also the less well known nocebo effect, in which a person experiences negative effects that are unrelated to any active ingredient in their treatment.
The exact mechanisms behind the placebo and the nocebo aren’t well understood, but it’s clear that the expectations of the recipient are important. Tell someone that a pill will cure their back pain, and they may experience pain relief, even if that pill was full of sugar. Tell the same person that the pill will give them headaches, and they are more likely to report headaches than if you had said nothing.
Analyses suggest that the placebo effect may be becoming more powerful. One study looked at 84 placebo-controlled trials of painkillers that took place between 1990 and 2013. They found that at the start of those trials, the real painkillers outperformed the painkillers by about 27%. Yet by 2013, they only outperformed the placebo treatments by about 9%. The absolute effectiveness of the real treatments didn’t change much over this time period, so this effect couldn’t be explained solely by painkillers becoming less effective. Rather, the placebo effect seemed to grow in strength. However, this isn’t the only interpretation possible.
Though the placebo effect seemed to grow in size, the effectiveness of the painkillers did not. The benefits of a placebo effect should apply even when taking the active compound. However, the data shows the placebo effect ‘stealing’ effect size from the real drug. This has made some people sceptical, as they argue that the effects should be additive or synergistic – that is to say, if the placebo effect was really becoming more powerful, then the absolute effect of the painkillers should also be becoming more powerful.
As a counterpoint, not all drugs work synergistically. In clinical trials, it is generally assumed that the placebo effect and the effect of the drug add up, meaning that the drug effect minus placebo effect equals true drug effectiveness. However, this isn’t necessarily true, especially when the placebo effect and a drug are both tapping into the same biological mechanism – the release of natural painkillers (endorphins) for example.
Assuming the placebo effect is getting stronger, what could be the cause? The researchers conducting the aforementioned analysis found an interesting clue: the placebo effect only seemed to be growing in the United States, not in other countries. This could be because the US is one of the few countries where drugs may be advertised directly to consumers. This means that improvements in drug marketing over the years could more directly impact expectations of consumers and thereby boost the placebo effect. Another suggested explanation is that drug trials conducted in the US tend to be larger, longer and more expensive. The ‘glamour’ of such trials might provide another route by which the strength of the placebo effect could be enhanced. Indeed, there is data suggesting that larger and longer trials produce stronger placebo effects.
Can you fool your brain? More or Less Podcast: https://www.bbc.co.uk/programmes/p0bm79m2
Increasing placebo responses over time in U.S. clinical trials of neuropathic pain: https://doi.org/10.1097/j.pain.0000000000000333
Placebo Effect Grows in U.S., Thwarting Development of Painkillers: https://www.scientificamerican.com/article/placebo-effect-grows-in-u-s-thwarting-development-of-painkillers