Abstract
New drug treatments, new indications for older drug treatments, lower thresholds for treating risk factors in preventative medicine, and an ageing population acquiring multiple pathologies all contribute to the development of polypharmacy. Longitudinal studies document the rise in prescribed medications, particularly in the elderly. The potential dangers of adverse drug reactions and interactions, poor adherence and confusion associated with ever-increasing polypharmacy are likely to worsen. Strategies to reduce prescribing will obviously decrease the dangers of polypharmacy. These include more considered prescribing when contemplating additions to patients’ already lengthy prescription lists, and external reviews of medicine lists by a doctor or pharmacist. Despite such strategies, polypharmacy seems inevitable and considerations must be given to simplifying patients’ multiple drug administrations using single-daily-dose regimens, fixed-dose combination pills, calendar-blister packaging and pill organizers.
Introduction
In developed countries, increasing numbers of drugs are now available to combat many chronic illnesses, and more preventative medicines are prescribed for conditions such as osteoporosis, ischaemic cardiovascular and cerebrovascular disease. Since most chronic diseases are associated with older age, the elderly are the main target for this increase in prescribing. Apart from advancing age, other factors leading to increased drug prescribing include newer treatments for diseases such as Alzheimer's disease, wider indications for various cardiovascular drug classes, and lower thresholds at which conditions such as hypertension and hypercholesterolaemia are now treated. 1 The increased use of primary and secondary preventative prescribing strategies, particularly in atheromatous cardiovascular disease has led to many patients taking long-term statins, antiplatelet drugs or warfarin, consistent with the wider indications for such drugs. 2,,3
Scale of the problem
In the UK, where older people make up a fifth of the population but consume almost half of prescription items, 4 adults aged >65 years take a mean of two daily prescribed drugs. 5,,6 In the >75 years age group living in the UK, this mean daily drug usage increases to 2.5. 6 In comparison, in community studies, people over 75 years old consume a mean 3.5 drugs daily in Northern Italy, 7 and four drugs daily in Denmark. 8 Most community studies of drug usage show that women take more prescribed drugs than men.
Polypharmacy is defined as the use of five or more drugs, and is prevalent in more than 10% of community-dwelling people aged >65 years in the UK. 4,,6 The prevalence of polypharmacy rises to 15% in UK residents over 75 years old. 6 Multiple drug usage is common in all developed countries; in the US, polypharmacy is found in as many as 40% of those older than 65 years. 9 Nursing home residents are a small but important group of patients who ingest many daily drugs, taking an average of 6–8 drugs daily. 10,,11
The increase in community prescribing
To quantify this ever-increasing problem, community studies in Nottingham, 12 Finland, 13,,14 the Netherlands, 15 USA 16 and Sweden 17,,18 have documented the increase in the number of drugs taken in primary care over time. Although these studies show marked variations in prescribed drug frequencies, they all show increases in the number of drugs prescribed over time. For example, a Dutch general practice study of patients >65 years old documented a mean of 1.3 drugs per patient in 1994, increasing to 1.8 drugs per patient in 1999, 15 while a Finnish community study of similarly aged individuals showed that the mean number of prescribed drugs increased from 3.1 in 1991 to 3.8 in 1999. 14 In a Swedish longitudinal study, 70-year-old residents of Gothenburg took a mean 3.2 drugs in 1971 and a mean 3.7 drugs in 2000. 17 The increases in drug prescribing are typically in anti-thrombotic drugs, sex hormones, angiotensin-converting-enzyme inhibitors, acid suppressors and lipid-lowering drugs. 18
The increase in hospital prescribing
Fewer data are available on the actual numbers of drugs taken by hospitalized patients. In a Norwegian study of drug-related problems, in-patients took a mean 4.6 drugs at the time of admission. 19 Hospitalized Swiss in-patients receive a median of six drugs daily. 20 Patients leaving the general medicine department of a teaching hospital in Boston, USA, are discharged with a median of eight drugs. 21 In medical patients acutely admitted to a UK district hospital, the median number of prescribed drugs taken on admission doubled from two in 1994, to four in 2004. 22 Patients were discharged with a median of three drugs in 1994 and five drugs in 2004. Correspondingly the median number of daily drug administrations on discharge increased from four to eight over the decade, with some patients now being discharged with more than 20 different daily drug doses. 22
Patients’ more detailed drug regimens are symptomatic of the increased complexity of modern medicine. For example, a patient with myocardial infarction 15 years ago might have been discharged from hospital with aspirin, a beta-blocker and nitrolingual spray. Now such a patient will also routinely receive a statin and also possibly an angiotensin-converting-enzyme inhibitor, an omega 3 fatty acid supplement and clopidogrel. Diseases such as type 2 diabetes and heart failure increasingly demand more complex drug regimens, and polypharmacy seems difficult to avoid. It is hardly surprising that as each new edition of the British National Formulary gets fatter, primary care computerized prescription lists continue to lengthen, and hospital in-patients now frequently have more than one drug chart.
Dangers of polypharmacy
Complex multiple-drug regimens lead to poor medication administration routines with non-compliance, therapeutic duplication, confusion between generic and trade names, 23 and more adverse drug reactions and drug interactions. It is estimated that approximately 5% of hospital admissions are linked to adverse drug reactions. 24–27 Adverse drug reactions are more likely to occur with polypharmacy, 28,,29 in the elderly 25 and in women. 20,,25,27 Adverse drug reactions occur in 5–10% of hospital inpatients, 20,,24,26,27 and are associated with increased length of stay and costs. 20,,30 Even the transition from out-patient to in-patient can be associated with prescribing transcription errors, and these are more likely with polypharmacy. 31,,32
Strategies to reduce polypharmacy
Many polypharmacy regimens represent sound prescribing, but there is also inappropriate prescribing, particularly in the elderly. 33–35 In the USA, criteria for inappropriate prescription drug usage among nursing home residents 36 have been extended to promoting improved drug therapy in elderly persons in all settings. 35,,37–39 Central to such criteria are lists of drugs associated with worse outcomes and ideally avoided in the elderly. Anxiolytic, antidepressant and hypnotic drugs feature prominently on these lists. Although there is some evidence of a decline in inappropriate drug prescribing, 39 attempts to reduce polypharmacy in general have had limited success. Some of the most successful strategies to reduce the numbers of drugs taken by elderly patients in the community have involved pharmacists reviewing patients’ medication lists and then discussing changes face-to-face with the prescribing doctor. 40,,41 Studies of interventions communicating pharmacists’ written advice on drug list review have been less successful. Although visits to patients’ homes may uncover unrecognized problems with medication usage, 23 such home-based medication reviews do not always improve outcomes. 42 Since older people residing in nursing homes are usually on more drugs than older people living in their own homes, attempts to review and reduce medication lists in this setting may be more fruitful. 43,,44 In the US, it is mandatory for nursing homes to employ a pharmacist to regularly review prescribed medication lists.
Clinicians considering adding another drug to a patient's medication list must consider whether the benefit will outweigh possible harm. Hospital specialists should look beyond the single disease being managed to the needs and whole health of the patient. However, little is known about the net effect on health improvements when one multi-drug regimen (e.g. for cardiovascular risk) is added to another (e.g. for osteoporosis). Hospital doctors should clarify to a patient's general practitioner the indications for a new drug therapy and, particularly when the patient is no longer to be under hospital review, its likely duration.
Specialist societies should specifically advise on whether the benefits of some interventions are readily extrapolated to the very elderly patient. For example more information is needed about the benefits of starting statin medication in patients over 85 years old, 45,,46 and a better awareness of the number needed to harm relative to the number needed to treat is required when elderly patients are commenced on antiplatelet agents or warfarin.
Despite attention to the above measures, increased polypharmacy in the elderly seems inevitable in an ageing population acquiring multiple pathologies. In the face of this, simplifying patients’ multiple drug administrations must be addressed. Single daily dose regimens and using one drug to treat more than one disease (e.g. hypertension and angina) will simplify drug routines. Fixed dose combination pills, calendar-blister packaging and pill organisers such as Dosett boxes may improve medication adherence, but these strategies have not been rigorously tested. 47 Polypharmacy, particularly in the elderly, is here to stay, and efforts to minimize its dangers must be intensified.
