How many pills are too many?

“It is an art of no little importance to administer medicines properly: but, it is an art of much greater and more difficult acquisition to know when to suspend or altogether to omit them.” Philippe Pinel 1745-1826.

As a teenage medical student, I struggled to understand the nature of my future trade. The penny finally dropped in the third or fourth year of my studies. The practice of modern medicine is largely about drugs.

Unfortunately, drugs are dangerous. An estimated one-fifth of all emergency admissions in the elderly are drug-related, and it is thought that 140,000 people are hospitalised in Australia each year from “medication misadventure”.

This is a startling amount of misadventuring - although, after a couple of decades in the game, I have decided that any medicine, herb or complementary medicament that is guaranteed 100 per cent safe is also guaranteed 100 per cent useless. Even placebos create multiple, unpredictable effects on an individual’s body.

Invariably, useful drugs sometimes cause harm. This means that both doctors and patients should realise that a reasonable treatment for a serious condition is not always a reasonable treatment for a mild case. Medication should be safer than the affliction it treats.

Polypharmacy

“The greater number of simples that go unto anie compound medicine, the greater confusion is found herein, because the qualities and operations of verie few of the particulars are thoroughlie knowne”. William Harrison 1534-1593.

Polypharmacy is the use of multiple medications by a patient. Surveys suggest up to one third of very elderly patients take six or more medications. Many people with disabilities are in the same situation. Understanding what needs to be taken, and when, is difficult enough for the doctor let alone the patient.

The computer software I mostly use for patient notes allows 13 current prescriptions to be viewed at one time. The programmers obviously thought this would be sufficient. To see more than this number of medications you need to scroll down within a text box. Disconcertingly, I do lots of scrolling.

Polypharmacy creates more problems than just financial costs and difficulties swallowing mountains of pills. Most notably, there is a high risk of drug interactions and side effects. This risk is said to rise exponentially as the number of drugs taken increases. Many people would be surprised at how little is known about the effect of mixing just two pharmaceuticals - let alone a dozen or more.

Particularly in patients with communication problems, side effects can go unnoticed or get misinterpreted as a natural deterioration in their condition. Ironically, when side effects are detected, the medical reflex is often to treat these with extra drugs.

Lies, damned lies and statistics

“All who drink of this remedy recover in a short time, except those whom it does not help, who all die. Therefore it is obvious that it fails only in incurable cases.” Galen c.129-c.216.

The science underlying modern pharmaceuticals gets distorted by commercial considerations. Manufacturers quite naturally seek to present their products favourably, for instance, by highlighting relative risk reduction when absolute risk reduction gives a more accurate picture of a drug’s efficacy. If trials suggest a medication will reduce a patient’s risk of stroke over the next five years from, say, 4 per cent to 3 per cent then the relative risk reduction is an impressive-sounding 25 per cent (the risk reduces by one fourth) but the absolute risk reduction is a measly 1 per cent (one chance in a hundred).

Even more useful in understanding a drug’s therapeutic impact are figures known as Number Needed to Treat (NNT) and Number Needed to Harm (NNH). NNT is the inverse of the absolute risk reduction and indicates the number of patients who need to receive a treatment for one patient to achieve the desired benefit. For instance, an NNT of five means if five patients receive a treatment then one patient benefits.

Number Needed to Harm is the number requiring treatment before one patient is harmed. In many clinical situations, it is pretty much unknown. Try asking your doctor for the NNT and NNH of treatment you receive. They probably won’t know. I usually don’t.

Low NNTs are good whereas low NNHs are bad. Highly effective treatments, for instance antibiotics for susceptible infections, have excellent NNTs under two. Preventive measures, for instance drugs to reduce high blood pressure or high cholesterol, often have disappointing NNTs of over 100 in all but the very highest risk groups.

With so many patients on so many drugs, it is worth considering whether every drug they take is actually essential. For instance, a patient on ten drugs with respectable NNTs of five would appear to have about one chance in ten million that every drug being taken is of benefit and over one chance in ten that absolutely none of the ten drugs taken are helpful.

Incidentally, the NNT for regular exercise to prevent a heart attack is perhaps about three. In other words, compared with high-tech drugs, exercise is vastly more effective at preventing heart attacks and is almost certainly less harmful. No wonder an apocryphal tsar had an interesting solution when he discovered his most disease-ridden province also had the most doctors. He killed the doctors.