Researchers in the United States have recently reported a study that suggests that paracetamol may dampen people’s emotional reactions. It would be reckless to come to any firm conclusions on the basis of a single study done on students, but the report may prompt people to give more thought to the potential side-effects that accompany the drugs they take every day. Like millions of other people around the world, I feel well most of the time; but without the two drugs I take – a diuretic and a statin – my blood pressure and my cholesterol would be higher. And we know from systematic reviews of randomised trials that my risk of heart attack and stroke would be higher, too.
Most of the drugs that lower blood pressure have similar efficacy levels, but they differ when it comes to side-effects. The drug I started taking caused an irritating, chronic cough, which disappeared when I switched to an inexpensive diuretic. Side-effects of drugs are important to everyone, but particularly to people expected to take them for a lifetime – and they deserve greater attention than they have received from researchers and regulators.
How about unwanted effects of statins? Trials have shown that statins can reduce heart attacks and strokes, but, very rarely, they cause a serious muscle breakdown. I haven’t experienced that, but since I started taking statins I feel I may have developed some muscle weakness. Might this be caused by these drugs? Although the drugs may be causing my symptoms, they may equally be due to something else – for example, walking and cycling only in “unhilly” Oxford.
As a passably healthy person who is expected to take drugs for the rest of my life, I want to find out if the muscle weakness I am experiencing is likely to be due to the statin I’m taking. Unfortunately, the available information from trials doesn’t provide solid evidence one way or the other. So what to do? What if I stopped taking the statin and I stopped experiencing muscle weakness? Would that mean that the statin had caused the problem? Or might I have just persuaded myself that there had been a change in my symptoms? Whatever the cause of the reduced symptoms, I would be forced to reconsider whether the possible adverse effects of the drugs on the quality of my life outweighed their relatively modest beneficial effects. This is clearly an unsatisfactory situation.
To find out whether my muscle weakness is due to the statin, or my imagination, or to some other cause, I would need to do personal, unbiased research. In jargon terms, what I need is a randomised, placebo-controlled, n-of-1 crossover trial. In such a trial, I would be randomly allocated successive periods of a few weeks to either continue taking my statin, or instead, to take an apparently identical dummy pill, recording my muscle symptoms throughout. After several crossovers, I would compare the frequency of my recorded symptoms during the periods I was taking statin, with the periods I was taking the dummy pill. The results would indicate whether the statin was likely to be the cause of the muscle weakness and so help me decide whether or not to consider abandoning the drug.
Nice has recently recommended that another 3 million well people in England and Wales who are moderately more likely than average to experience a heart attack or a stroke should take a statin for the rest of their lives. There is solid evidence that these drugs will, on average, decrease heart attacks and strokes. For any particular individual among the extra 3 million, however, the likelihood of experiencing this benefit is quite small: every year, three out of a thousand people taking statins would be expected to avoid a heart attack or stroke. Some people might regard this as too modest a dividend from becoming a “patient” and taking a drug for a lifetime – particularly if one pays for taking it by suffering unwanted effects.
This is just one example of our need for more reliable information about the possible side-effects of widely used drugs. Side-effects of drugs should matter to everyone, and people who are basically well have a particular interest in making informed choices about whether to take drugs for a lifetime. Research to address inadequately assessed, widely used drugs should be an expected component of good medical practice. And for that to happen, some of the many obstacles to integrating research in everyday practice will have to be removed.
