Just say no to drug combos

Most of us believe that, as we get older, we’re going to suffer increasing disability and illness, and medicine convinces us that it’s just a natural part of ageing. To deal with the symptoms of decline, we’re given a variety of prescription drugs - usually in combination. It’s now commonplace for the over-65s to be taking five or more medications on a regular basis.

Yet, far from being a fountain of youth, prescription drugs - especially in combination - may well be hastening the problems of old age: physical frailty, loss of vital-organ function and even mental decline.

The tendency of doctors to dole out multiple drugs to the elderly is worrying because this population group is getting larger by the day. Today, 13 per cent of the US population is over 65, a figure set to rise dramatically in the coming years. Yet, seniors consume, on average, 30 per cent of all prescription drugs (Health Prom Dis Prev, 1992; 8: 127-41). In the UK, the over-65s account for 18 per cent of the population, but nearly half of all prescription drug use (Pharm J, 1997; 259: 686-8).

And these figures are conservative as drug use among the elderly is believed to be grossly underreported.

Doling out drugs
The problem lies in the way doctors approach healthcare in the elderly, and their sketchy knowledge of which drugs are both effective and appropriate for this age group. A recent large-scale study of more than 765,000 seniors showed that more than one-fifth of their prescriptions were inappropriate for their age group (Arch Intern Med, 2004; 164: 1621-5). Ten years ago, a widely publicised report revealed that nearly a quarter of elderly Americans were being prescribed one or more medications that were countraindicated for this patient population (JAMA, 1994, 272: 292-317).

But the most dangerous practice of all - practised all over the world - is polypharmacy, where several different drugs are prescribed at once without sufficient understanding of how these drugs react in combination.

Most older Americans, for example, take an average of three to five drugs (J Am Geriatr Soc, 2001; 49: 277-83), and that doesn’t include over-the-counter medications or herbals. In Canada, 91 per cent of older patients are taking one or more drugs (prescribed or over the counter) - the average per patient was more than four apiece (Ann Emerg Med, 2001; 38: 666-71). In the UK, at least a third of patients over 75 are taking four or more prescription drugs (BMJ, 2004; 329: 434). An Australian survey of more than 200,000 veterans found that:
* more than half were taking more than five separate drugs
* one-fifth were taking more than 10 drugs
* around one in 14 was taking more than 15 drugs
* one in 30 was taking 20 drugs (Aust NZ J Public Health, 1997; 21: 469-76).

While this kind of reckless prescribing used to be confined to nursing homes, it’s now a risk faced by anyone over the age of 50. Besides ignoring the inherent dangers of interactions between drugs, doctors increasingly prescribe drugs ‘off label’ - that is, for conditions and at dosages different from those approved, a well-known major cause of adverse drug reactions.

As the number of drugs taken increases, the risk of adverse effects increases exponentially. Compared with taking only one drug, the risk of ill effects when taking five increases by a further 4 per cent. But if 16 drugs are taken, the added risk skyrockets to 54 per cent (Clin Geriatr Med, 1990; 6: 293-307).

Polypharmacy: a new illness
So common are drug side-effects that doctors now recognise ‘iatrogenic disease’ - doctor-induced disease - from prescribed drugs as a leading cause of illness and death.

Indeed, the Journal of the American Medical Association, the leading scientific publication for the US medical profession, announced that adverse drug reactions were the leading cause of death in hospitalised patients, after the other big killers: heart disease, cancer, stroke, lung disease and accidents. Also, adverse drug events in older patients led to hospitalisation in 25 per cent of those 80 years and older (JAMA, 1998; 279: 1200-5).

In the US, it’s been estimated that, for every dollar spent on drugs in nursing homes, another is spent treating the iatrogenic illness caused by those medications (Arch Intern Med, 1997; 157: 2089-96).

Worse, doctors may mistake an adverse drug effect for a new illness, and end up piling on even more drugs to an already overcrowded regime - the so-called ‘prescribing cascade’ - which, of course, leads to even more side-effects (BMJ, 1997; 315: 1096-9).

The older body
Most medicines are tested on healthy people in their 30s and 40s because, like children, the elderly are not considered ideal subjects for medical study. This is because an older body reacts differently to medication.

In the elderly body, four aspects make drug use potentially risky:
* absorption
* distribution
* metabolism
* excretion.

Contrary to typical belief, absorption is not generally affected by age. Older people absorb medications fully, though perhaps more slowly. But once in the system, drugs may behave differently from how they would in a younger body.

In older people who are overweight, fat-soluble drugs can accumulate in fatty tissue and reach toxic proportions. Similarly, the uptake of water-soluble drugs may be slowed by increased fatty tissue, but their effects are greater and longer-lasting. In the elderly, the metabolism of drugs in the liver and excretion through the kidneys may also be slower or less complete, again with more risk of toxicity and damage to those organs.

Breaking the habit
Doctors and elderly patients - and the patients’ families - need to work together to break the habit of polypharmacy. Sadly, many physicians are loath to change their ways. A study from Australia showed that, even when general practitioners were presented with evidence of their own inappropriate prescribing habits over a two-year period, they still did not change their ways (BMJ, 1999; 318: 507-11).

This entrenched attitude makes it more incumbent upon the older patient himself to be a strong medical consumer and do his own homework about each drug being taken (see box), and to insist that your doctor cut out any drugs you don’t need.

Around half of the most popular prescription drugs (such as sedatives and mood enhancers) interact with alcohol (Generations, 1988; 12: 9-13). The older patient needs to be especially vigilant about this interaction, even with over-the-counter remedies, as many of these themselves contain alcohol.

Not prescribing drugs for self-limiting or lifestyle health problems is also important. Many of the ailments affecting seniors are linked to behavioural or lifestyle factors such as smoking or alcohol consumption. Likewise, many of the degenerative diseases that plague older adults can be traced back to six factors of unhealthy ageing:

* Altered mitochondrial function due to oxidative stress. Mitochondria are the energy powerhouses of the cell, where nutrients are broken down to release energy for cell repair, defence mechanisms, neuromuscular function, and other processes that maintain the body and help resist ageing. Mitochondrial disorders such as fibromyalgia, heart problems, immune deficiencies, and central and peripheral nervous system problems such as Alzheimer’s and dementia are associated with accelerated ageing (N Engl J Med, 1995; 333: 638-44).

* Increased protein glycation. In this process, blood sugar (glucose) is turned into glycated proteins, including glycohaemoglobin, which is involved in the control of blood sugar in diabetics - but too many of these proteins can lead to poor glucose control. Other proteins in the body become glycated when there is poor control of insulin and glucose metabolism. This can lead to periodontal disease and tooth loss (J Periodontal Res, 1996; 31: 508-15), skin ageing and wrinkling (J Clin Invest, 1993; 91: 2463-9), and an increased risk of heart disease (J Clin Invest, 1995; 96: 1395-402).

* Chronic inflammation. This begins in the gut, triggered by allergens or parasites, and can give rise to local and systemic immune reactions with gut-associated lymphoid tissue (GALT). Among genetically susceptible individuals, chronic inflammation is associated not only with gastrointestinal and liver-related disorders, but with the risk of Alzheimer’s and heart diseases as well (Neurology, 1997; 48: 626-32; N Engl J Med, 1997; 336: 973-9).

* Poor metabolism of homocysteine (an amino acid) increases the risk of heart disease (JAMA, 1997; 277: 1775-81), stroke and dementia among certain individuals.

* Compromised detoxification means that toxins accumulate in the body, including drugs as well as environmental pollutants that may be toxic in themselves, and also contribute to free-radical production.

* Altered immunity may result from all of the above. As immunity declines, susceptibility increases to infectious agents as well as to allergens.

These problems can all be modified through diet and exercise (see boxes on page 2 and above).

If your doctor doesn’t tell you - or, more likely, doesn’t know - you also need to find out which drugs are not appropriate for seniors (see box, page 3). It’s now known that one in four and one in seven older patients are receiving at least one inappropriate medication (Ann Pharmacother, 2000; 34: 338-46). The most often prescribed risky drugs are long-acting benzodiazepines (tranquillisers and sleeping pills), the antiplatelet drug dipyridamole (Persantine), the pain reliever propoxyphene (Darvon) and the tricyclic antidepressant amitriptyline (Elavil).

Staying alert for gradual changes that may signal a harmful side-effect is essential. Important ‘red-flag’ symptoms include changes in mood, energy, attitude or memory. Too often, these alterations are overlooked, ignored or just chalked off to ‘old age’ or senility. But virtually every heart drug, blood pressure drug, sleeping pill and tranquilliser can trigger these symptoms. So, when a psychological symptom appears - in yourself, a senior patient or a loved one - look to the medications first.

Cutting down on drug use
By asking a few simple questions, you can avoid the prescribing cascade. If you don’t feel confident enough to challenge your physician, take a supportive family member with you.

* Is this illness minor or self-limiting? If so, it may be best to go without drugs.

* Can I get better with lifestyle changes? Losing weight, stopping smoking, curtailing alcohol use and more frequent exercise can all provide substantial benefits, often working as well as - or even better than - prescribed drugs.

* How long has it been since the doctor has reviewed the drugs I am taking? Researchers suggest regularly bagging up all the medicines you’re using (including over-the-counter ones) and taking them to your doctor for a review. Check whether any of the drugs you’re taking can be discontinued.

* Do I need all these drugs? Chances are, the answer is no. Simplifying your drug regimen to include only those that are proven and essential will reduce the risk of drug-induced illness.

* Can the dose be reduced? Challenging your doctor on the dosage and frequency of the prescribed drugs can often result in a reduction, without any loss of benefit.

* What are the adverse effects of this/these drugs? Make sure that your physician has given you a comprehensive list of the potential adverse effects of your medications. Read all the information that comes with a drug so that side-effects are not ignored or wrongly put down to old age.

* Is there a less toxic drug that can do the same thing? There is almost always an alternative medication. Insist on the safest drug possible.

* Should I report this adverse effect? The answer is always yes. Underreporting of adverse drug reactions, or wrongly attributing such symptoms to old age, means that the extent of the problem of polypharmacy will remain largely hidden.

Healthcare in the over-65s rests on the false assumptions that to be old is to be sick and that medicine will cure these problems. To reach your three score and 10, you have a better prospect by looking to your diet and exercise, and saying no to drugs - especially a handful of them.

Pat Thomas