Nocebo: statins and side effects

Have you ever heard of a nocebo? Possibly not, but it’s effectively the opposite of a placebo: you expect to experience side effects when you take a drug, so you do! And a study out this week suggests this nocebo effect could be playing a significant role in the difficulties some people have with taking cholesterol-lowering drugs called statins, as Katie Haylor has been hearing...

James - Most of the time when patients suffer side effects from statins, although they are real, they are probably not caused by the statin molecule themselves, but rather by the act of taking a tablet.

Katie - That's cardiologist James Howard from Imperial College London. James and colleagues have recently published the findings of a clinical trial called SAMSON, which sought to better understand why some people have such a difficult time taking cholesterol lowering drugs called statins.

James - Statins are actually one of the most prescribed medicines in the UK because they can help prevent heart attacks and strokes. But so many of our patients suffer from side effects, and some people have estimated that half of patients have had to stop taking statins within two years of being prescribed to them.

Katie - The team recruited 60 people who'd all actually stopped taking statins in the past due to side effects. These can be wide ranging in severity and type, but in this study, 60% of people had experienced muscle aches and pains.

James - We gave them a suitcase, and inside that suitcase there were twelve jars. And four of those jars contained these statin tablets; four of the jars contained what we call placebos, which are just sugar tablets that look identical to the statins; and four of them were empty. And for every month of the following year, they were told to start a different jar in a random order that we told them. And we also - if they didn't own their own - gave them a smartphone, and they used that to tell us every day, on a scale of 0 to 100, how good or bad they felt.

Katie - Crucially neither the participants nor the scientists knew who was taking what throughout the study.

James - The patients of course knew when they weren't taking tablets, which was the case for four months of the year. But for the other eight months of the year, they didn't know if the tablets they were taking were statin tablets or the sugar tablets.

Katie - And it was tough going for some.

James - 49 of them managed to complete the full year. That means 11 of them didn't. And of those, around half of those had to stop because they found the side effects so bad they didn't want to carry on.

James -  Now the 49 that did finish, they also occasionally had to stop their tablets because the side effects were so bad, but the next month they were willing to come back and keep doing the experiment.

Katie - Well the team sat down with the participants and showed them the scores of how they'd been feeling throughout the year and which tablets - statins, sugar pills, or none - they'd been taking.

James - When people don't take tablets, they don't get very many symptoms at all. When they take statins, they actually feel much worse, but they feel 90% as bad taking the sugar tablets. So what we think is going on is that when people take statins, they are concerned that they will feel worse. And actually, this does make them feel worse. And we call this the nocebo effect.

Katie - The team actually found that explaining this nocebo effect to the people on the trial had a pretty big impact.

James - When we sat down with patients and talked about their symptoms and showed them their results, half of them were able to go back on to statins, without problems, and were still taking them six months later. For the half that aren't back on statins yet, a lot of them say they actually want to go back, but because of the COVID crisis and things like that, they haven't been able to make appointments with their GP doctors. So only around half of half of our patients refuse to go back on the statins because they felt they really did have side effects.

Katie - So what about that 10% that wasn't reflected in the placebo group? Are they drug-related side effects?

James - So it's a little bit difficult to say that because whenever you make a measurement in a clinical trial, you know you're not going to be quite precise enough. And because of that, we are saying most side effects seem to be caused by this very interesting nocebo effect. Some patients do get satin side effects caused by the drug themselves because that's the case with all drugs. We're just saying it's probably a lot rarer than we previously thought. By sitting down with patients and showing them the science, you can get them back on tablets that previously they haven't been able to take. So communication is the most important thing.