Polypharmacy, appropriate and inappropriate

I have seen it asserted that ‘polydactyly’ is an inappropriate word, because it means many digits (fingers or toes), and we all have many digits. This analysis is superficial. The Greek word $\pi o\lambda {\upsilon }^{´}\varsigma$ (polus) had several meanings, such as many, mighty, long, and wide. The English prefix poly-usually takes the first of these meanings; polymyalgia means pain in many muscles, polyneuropathy disease of many nerves. However, $\pi o\lambda {\upsilon }^{´}\varsigma$ could also mean too much or too many. We all have many red blood cells, so polycythaemia means having too many; someone who drinks too much has polydipsia; and polydactyly means too many fingers or toes. But there is one word in which both meanings are possible — polypharmacy, the prescribing of either many drugs or too many drugs. The term is usually used in the second of these senses, and pejoratively. But polypharmacy can be beneficial, and by itself is not the real problem—the problem is whether each drug has been prescribed appropriately or inappropriately, both individually and in the context of the whole prescription.^1,2

There are many conditions in which the combined use of three or more drugs is beneficial and appropriate. Diabetes mellitus is often treated with several drugs at once.³ In tuberculosis we combine three or four different drugs, to prevent the emergence of resistant mycobacteria. We use three drugs to eradicate Helicobacter pylori from the stomach and three or four in the HAART regimen used to treat AIDS. A striking example of potentially beneficial polypharmacy is the ‘Polypill’, with six proposed ingredients—aspirin, a statin, and folic acid, plus three antihypertensive drugs.⁴ The antihypertensive drugs are recommended in half the usual doses, reducing the risks of adverse effects, which are distinct for the different types of drugs, while multiplying the therapeutic benefit, since all lower the blood pressure. It has been claimed, from predictions based on a large amount of published evidence, that if everyone over 55 years old took the ‘Polypill’, the burden of heart attacks and strokes in the population would be reduced by over 80%.⁴ The risk of any adverse effect is an estimated 17% and of an adverse effect serious enough to warrant withdrawal 1–2%; aspirin is the major contributor to these figures, and those unable to tolerate it could beneficially take the other five ingredients with little risk.

On the other hand, inappropriate polypharmacy is common and is associated with an increased risk of adverse drug reactions and interactions. For example, if a patient takes eight medicines, each of which carries an independent 5% chance of an adverse drug reaction, the overall risk of an adverse reaction is 34%, and there are 28 potential drug–drug interactions, taking only pairs of drugs into account.

In this issue of the Journal, a group from the Netherlands (GPs, community and clinical pharmacists, and geratologists) report their findings in a survey of 102 elderly patients in primary care, each of whom was taking four medicines or more (755 medicines in all).⁵ In 96 patients they detected 457 instances of inappropriate prescribing that they considered to be clinically important or potentially so. In about 60% of these the medicine was not useful, had been used in the wrong dose or for the wrong duration, or was not judged appropriate for use in elderly people.

Inappropriate prescribing was not the only problem. There were also many instances of inappropriate non-prescribing, and in 23% of the patients they were considered to be important. They included failure to give aspirin to patients with ischaemic heart disease or an ACE inhibitor to patients with cardiac failure—failure, indeed, all round.

There are some problems with this study. For example, of the 10 categories of inappropriateness that the authors defined, two were contradictory. One included, ‘medicine[s] used for treatment of a side-effect caused by another medicine, [for example] omeprazole for treatment of stomach problems probably caused by ketoprofen …’, but another was, ‘omission of drug therapy that is indicated for the treatment or prevention of a condition, [for example] lack of prescribing a laxative to a patient using an opiate’. Furthermore, the clinical importance attributed to inappropriate prescribing was in some cases doubtful. For example, the authors assert that co-prescription of digoxin and diuretics should not cause problems if potassium concentrations are checked regularly; however, one cannot check the potassium often enough to ensure avoiding a harmful interaction (for example, if the patient one day takes the wrong dose of diuretic). A major problem of monitoring for adverse effects is that things are more likely to go wrong between tests.

However, the results of this study remind us that it is important to review our patients' medications regularly, whether they are young or old, in order to determine how appropriate they are, especially (although not only) if they are taking many drugs. How regularly such reviews should be performed is the potential subject of another study.

Conflict of interest

The author has stated that there are none.