Abstract
Polypharmacy is the use of several concurrent medications by one individual. It is an increasingly common phenomenon in an ageing population with multiple morbidities, and can often be a challenge for the GP. When used appropriately, medication can prolong life and aid symptom control. When medications are used unnecessarily, polypharmacy can have adverse effects, particularly on elderly patients. This article aims to help the GP manage patients on multiple medications, be aware of potential problems this may cause, and give guidance on medication reviews.
The GP curriculum and polypharmacy in the elderly
Understand the physical, psychological and social changes that may occur with age and relate them to the adaptations that an older person makes, and to the breakdown of these adaptations, e.g. when hearing, vision or cognitive function continue to worsen Understand the special factors associated with drug treatment, e.g. the physiology of absorption, metabolism and excretion of drugs, the hazards posed by multiple prescribing, non-compliance and iatrogenic disease
Polypharmacy
True polypharmacy is defined as the use of several different medications by one patient at the same time (Duerden, Avery, & Payne 2013). As patients now live longer, the number of medications one patient may take has also increased. Although polypharmacy can occur in both primary and secondary care, it is GPs who often take on the management of long-term conditions and prescriptions. GPs often face a difficult challenge to keep up-to-date with information about developments, so that they can not only provide the best treatment for their patients but also be aware of potential drug interactions and adverse effects.
How common is polypharmacy?
Polypharmacy appears to be on the increase. The prescribing cost analysis of England confirms a rise in the amount of medications dispensed in the community. In 2013, 1 billion medications were dispensed in the community, a rise of 3% from the previous year and at a net ingredient cost of £8.6 billion (Heath and Social Care Information Centre, 2014). Several reasons may be responsible for this rise: an ageing population; advances in medical management of diseases; and using medications in disease prevention.
A recent Scottish study of 300 000 patients showed the mean number of dispensed medications per patient had risen from 3.3 in 1995 to 4.4 in 2010, with those using over five medications increasing from 12 to 22%. In the population of over 65 year olds, the proportion of patients with polypharmacy was also particularly high, with 16.4% receiving 10 or more medications (Guthrie & Makubate, 2012). In the UK, 45% of prescriptions are dispensed to adults over 65 years in age (Wynne & Blagburn, 2010). A study of nursing home residents demonstrated an average use of eight medications per patient (Barber et al., 2009). Commonly prescribed items in the elderly population include aspirin, anti-hypertensives and statins.
Drug pharmacokinetics and pharmacodynamics
With age comes a significant change in drug pharmacokinetics and pharmacodynamics. These can be divided into changes in drug absorption, distribution, metabolism and excretion. There are a number of factors that contribute, including reductions in body weight, renal excretion and liver enzyme function (Milton, Hill-Smith, & Jackson, 2008). These changes are summarised in Fig. 1.
Mechanisms leading to pharmacokinetic variations of drug effects in the elderly.
The two most clinically significant changes relate to drug metabolism and excretion. First, the combination of reduced hepatic blood flow and reduced hepatic mass result in changes to the concentration of drugs metabolised by the liver (Brody, Larner, & Minneman, 1998). As a result, specific caution needs to be taken when prescribing drugs that are metabolised by the liver and have a narrow therapeutic window, such as warfarin, theophylline and phenytoin. Second, a reduction in renal clearance results in the reduced excretion of water-soluble drugs. Many prescribers are aware of this and know to adjust doses based on renal function. However, this can be misleading in older people, due to lower muscle mass causing the creatinine to remain within the ‘normal’ range, despite a significant impairment in the filtration rate. Therefore, specific caution is required and dose adjustment needs to be made to renally-excreted drugs, such a digoxin, lithium and gentamicin (Anathhanam, Powis, Cracknell, & Robson, 2012).
In relation to pharmacodynamics, the elderly are deemed to be more sensitive to the effects of certain drugs, particularly those that affect the central nervous system. As a consequence, drug classes such as benzodiazepines should be used with caution, and if absolutely necessary, then at a reduced dose to minimise the risk of falls and other adverse events (Milton et al., 2008). In addition, age is associated with decreased regulatory functions, therefore anti-hypertensives can more easily result in postural hypotension and opiates in respiratory depression (Brody et al., 1998).
Risk factors for polypharmacy
Factors that lead to increased polypharmacy can be split into those related to the patient, and those related to the physician. In the patient, the presence of multiple co-morbidities is a risk factor for polypharmacy and treating such patients appears to have become the norm in general practice. A recent cross-sectional study in Scotland looked at 1 751 841 patients and explored the relationship between age, socio-economic status and sex, with multiple morbidities. It demonstrated that a quarter of all patients, and over half of patients with a chronic disorder, reported to have multiple co-morbidities. Multiple co-morbidities were also strongly related to age, and will become an increasingly more prevalent challenge in the ageing population of the UK (Barnett et al., 2012) (see Fig. 2). In the UK, the average age is expected to rise from 39.7 years in 2010 to 42.5 in 2035. The percentage of patients over the age of 85 years will rise dramatically, from 1 400 000 in 2010 to 1 900 000 in 2020 and 3 500 000 in 2035 (National Office for Statistics, 2012).
The number of chronic conditions related to age.
Patient behaviour and understanding can also contribute to polypharmacy. Poor patient knowledge of medications may lead to duplicate or unnecessary medications being prescribed by physicians who do not have access to their current or previous medication list. This may be a particular problem as patients move between primary and secondary care. It may also lead to a ‘prescribing cascade’, where a physician fails to realise that a new symptom is an adverse drug reaction or a side effect, and so another drug is deployed to treat this problem. Patients who see several different physicians at several different sites also increase the risk of duplicated medications or drug interactions.
The physician may also contribute to polypharmacy. A sometimes misguided perception that patients want to leave the consultation with a prescription can lead to inappropriate or unnecessary prescribing. Poor or inaccurate medication counselling by doctors can lead to patients taking medications incorrectly or for inappropriate lengths of time. Signing repeat prescriptions without proper review, failing to do regular medication reviews with patients, and a poor knowledge of drug interactions can also lead to polypharmacy or unwanted adverse drug effects (Abdulraheem, 2013).
Adverse effects of polypharmacy
Polypharmacy can have significant adverse effects on patients of any age, but an elderly patient is even more vulnerable. Polypharmacy can increase the occurrence of side effects, drug interactions, adverse drug reactions and non-adherence, and can also contribute towards the ‘geriatric syndrome’.
Examples of medications to be used with caution in the elderly.
Concurrent use of multiple medications can increase the risk of adverse drug reactions. Adverse drug reactions (ADRs) are reported to account for 6.5% of hospital admissions, of which 70% are avoidable. In 2008–09, more than 500 000 bed-days were attributed to adverse events caused by medicines, at a cost to the NHS of £235000000 (Royal Pharmaceutical Society, 2013).
ADRs may be sub-classified into Type A or Type B reactions. Type A reactions are predictable or related to the mechanism of action, for example, bleeding on warfarin, and this may occur if drug interactions raise the plasma levels of a medication. Type B reactions are unpredictable and unexpected, for example, anaphylaxis or Stevens–Johnson syndrome. The risk of ADRs is 15% with two medications, and increases to 58% with five medications and 82% with over seven medications (Masodi, 2008). The four most common drug groups associated with preventable drug-related admissions are reported by Howard et al. (2006) to be: anti-platelets (16%); diuretics (15.9%); non-steroidal anti-inflammatory drugs (11%); and anti-coagulants (8.3%).
Polypharmacy can also negatively influence medication adherence. In the elderly, non-compliance is stated as being as high as 50% (Social Care Institute for Excellence, 2005) and the likelihood rises with the number of medications prescribed. Poorer adherence with advancing age has been linked to a number of factors, such as the complexity of the therapeutic regimen, visual or hearing impairment, cognitive or functional impairment and social isolation (Osterberg & Blaschke, 2005). Poor adherence to medication regimes can lead to disease progression, poor symptom control, hospital admissions and even death. Between 11 and 30% of drug-related admissions are due to medication non-compliance, with significant cost to the NHS (Col, Fanale, & Kronholm, 1990)
Polypharmacy can worsen frailty, a term which refers to the collection of health problems an older adult may face. This includes delirium and cognitive impairment, falls and decreased functional ability.
Drugs are a common risk factor for delirium. Although delirium is often multifactorial, it is estimated that drugs alone can account for 12–39% of delirium cases. The most common medications to cause delirium are opiates, benzodiazipines and anti-cholinergics (Alagiakrishnan & Wiens, 2004). Medications with an anti-cholinergic effect can risk worsening a developing dementia. Potential culprits include some anti-histamines and oxybutynin. The Anticholinergic Cognitive Burden Scale (Indianapolis University Center for Aging Research, 2012) is a useful tool for GPs; it lists risky medication and gives them each a score from one to three. For each point, the risk of cognitive impairment may increase by as much as 46% over 6 years.
Falls in the elderly are common and can cause significant physical and emotional harm. Polypharmacy has been shown to increase the risk of falls in older adults, even after adjustment for age, disability, types of medication and co-morbid conditions (Ziere et al., 2006). Medications commonly involved included blood pressure medications, diuretics, laxatives, anti-cholinergics, hypnotics and benzodiazepines.
Polypharmacy has been associated with a general decline in functional ability in the elderly. A prospective study of community-dwelling older adults (412 women and 328 men) found that an increased number of prescribed medications correlated to an increased difficulty in performing activities of daily living (Magaziner, Cadigan, Fedder, & Hebel, 1989).
Under-prescribing in the elderly
Under-prescribing of drugs in the elderly can also be a problem. Doctors may restrict the use of potentially appropriate medications due to fears of drug-related problems. In many cases, drug use in the elderly may be even more effective than the young, as the baseline risk is higher and therefore numbers needed to treat may be less.
The HYVET study looked at the management of hypertension in the very elderly population. It included 3845 people over the age of 80 years, with a systolic blood pressure of over 160 mmHg and compared the outcomes of treatment with indapamide +/− perindopril, to those given placebos. The results showed a clear reduction in fatal and non-fatal strokes among those whose blood pressure was actively treated (Beckett et al., 2008). Similar results have been found in studies of the use of statins in older people (e.g. the PROSPER study). There has, however, been criticism that these trials only included relatively fit older patients, and therefore, the results cannot be generalised to the older population as a whole.
Importantly, despite these trials having potential flaws, they are extremely important in the world of geriatric medicine. Most medication trials actively exclude older patients, those with polypharmacy or multiple co-morbidities. Therefore, most of the clinical guidelines commonly used in both general practice and hospital medicine are based upon results derived from trials on a younger, fitter cohort than the majority of their patients. As a consequence, the trials may not pick-up on adverse drug events or interactions that occur in older people. It could be argued that we should have separate guidelines for older people, taking into account both the physiological changes and social aspects that impact on medication choices in this age group (Duerden et al., 2013).
Personal account of living with polypharmacy.
Reducing inappropriate polypharmacy: evidence-based tools
The 10 criteria of the Medication Appropriateness Index.
Opportunities to reduce polypharmacy in primary care
Reviews of medications, monitoring for side effects and blood test monitoring should be commonplace in the GP consultation. However, for more complicated patients, the GP may need to arrange separate appointments where both the doctor and the patient understand that the main purpose of the consultation is a medication review. Structuring the review around a clinical medication review, assessment of compliance and review of side effects can be helpful. It is also important to consider the frailty and expected life expectancy of the patient. For example, the use of certain cardio-protective agents, such as statins, is unlikely to provide much added benefit if life expectancy is less than 6 months. GP practices have a pharmacist who can work closely alongside a GP. Such pharmacists are often under-utilised in terms of assisting with complex medication reviews; however, their expertise can be invaluable. A randomised controlled trial demonstrated that a pharmacist located in a primary care clinic was able to provide education to both patient and prescriber, and also decrease polypharmacy and prescribing errors (Milos et al., 2013).
Other than allocated appointments for medication reviews, there are multiple other opportunities for GPs to look at polypharmacy. In 2014, NHS employers and the General Practice Committee agreed to have a named GP and a health check for all 75 year olds. This provides a longer appointment time to do a full geriatric assessment, where all physical, psychological and social needs can be addressed and a full medication review can be conducted.
In the UK, it is estimated that over 75% of patients over 60 years in age may be on repeat prescriptions (Duerden et al., 2003). Repeat prescriptions can provide convenience and ease for patients on several prescriptions. However, it can also pose significant risks to patients. Thorough review of all medications on a repeat prescriptions must take place before signing the prescription, including identifying when the last repeat was issued. Risks associated with repeat prescriptions include failure to identify drug reactions, medications used for unnecessary lengths of times, costs of drug wastage, and no face-to-face medication reviews that may identify problematic side effects. Such is the risk associated with repeat prescribing that the Medical Protection Society issued a ‘risk alert' and conducted a clinical risk assessment, finding that 95.7% of practices had problems with repeat prescribing (Medical Protection Society, 2012).
A GP must also be aware of the potential drug-related problems a patient may encounter following a recent hospital inpatient admission. More than 40% of medication errors occur because of poor medication reconciliation at transitions of care. In addition, discrepancies in medications at discharge are linked to poor adherence and increased risk of patient readmission (Redmond et al., 2013). Over 40% of hospital discharge summaries may never be received by the GP, with many patients’ regular medications stopped without a clear reason (Sharma, 2011). A GP must therefore be vigilant when reading summaries to spot medication changes, and where unclear, get clarity from the inpatient team on why medications may have been changed, stopped or started.
Many GP practices will have a nursing or residential home for whom they provide care. This is an excellent opportunity to look at polypharmacy. Studies in patients who live in care homes have made some useful suggestions for improving polypharmacy. First, they suggest having one named GP and pharmacist for a single care home, allowing better continuity of care. Accurate recording of omitted doses is important, and may be assisted by the use of an electronic prescription system (Barber et al., 2009). Nursing home patients are often frailer and more unwell, and a short life expectancy may mean that it is more appropriate to stop certain preventive medications.
A practical way to help patients who are taking multiple medications is to use monitored dose systems (MDSs), which include dosette boxes and blister packs. A recent Cochrane Review looked at data on over 2000 participants, and found that those using such systems took a greater proportion of their pills (Mahtani, Heneghan, Glasziou, & Perera, 2011). They also looked at specific outcomes, such as blood pressure and Haemoglobin A1c (HbA1c), and found that those patients using MDSs typically had lower values. However, not all the data was favourable, and therefore they concluded that these systems might be a low-cost way to increase adherence, but more research is needed to improve their design and use. In addition, a study of the use of MDSs in nursing home residents found that those using these systems actually had poorer medication usage. This was thought to relate to problems with their construction e.g. specific instructions going missing, drugs getting mixed up, or with the additional use of an acute treatment (Barber et al., 2009).
Key points
Drug metabolism in the elderly is different, due to changes in body fat, and renal and liver functions Polypharmacy is common, with 22% of patients taking over five medications Polypharmacy can cause ADRs, increased experience of side effects, poor adherence, and functional and cognitive impairments in the elderly Under-prescribing of appropriate medications is also a problem in the elderly Several evidence-based tools exist to assist doctors in reducing polypharmacy There are multiple occasions in primary care to reduce polypharmacy, including over-75’s health checks, reviewing repeat prescriptions and in nursing homes.