Polypharmacy means taking multiple medications.  The normal threshold for polypharmacy is the use of 4 or more different, regular (usually daily) medications.

Occasionally organisations use higher thresholds.  For example NICE guidance on multimorbidity (NG56) states that services “must use an approach to care that takes account of multimorbidity for people of any age who are prescribed 15 or more regular medicines”.  However, as the risk of adverse drug reactions and interactions increase with age and frailty, a lower threshold is appropriate for older people with frailty.

Causes of increasing polypharmacy

The main underlying causes of increasing polypharmacy are:

  • Our ageing population;
  • Increasing multimorbidity;
  • The implementation of clinical guidelines.

Longer life expectancy is leading to an increase in the prevalence and coexistence of long-term conditions, known as multimorbidity.  At the same time, a drive towards the universal implementation of evidence-based guidelines for individual long term conditions has increased prescribing of medications for cardiovascular, metabolic, respiratory and central nervous system conditions, in particular.  However, this guideline driven approach focuses upon individual condition management and often fails to take a holistic view or give due consideration to a person’s frailty or multimorbidity, even though age and comorbidity are often exclusions for the evidence base upon which single condition guidelines are developed.  Older people living with frailty are therefore very often subject to complex treatment regimes involving multiple medications.

Adverse impacts of polypharmacy

The adverse impacts of polypharmacy for the individual include:

  • Increased treatment burden
  • Direct adverse drug reactions
  • Adverse reactions resulting from drug interactions
  • Impaired treatment efficacy due to diminished adherence.

There are also adverse economic consequences through reduced cost effectiveness and increased direct and indirect healthcare costs.

As well as being frequent recipients of polypharmacy, older people living with frailty are also more susceptible to the problems associated with polypharmacy when compared to younger people and those without frailty.  The risks of adverse drug reactions and interactions are increased by age and frailty associated changes in pharmacodynamics (how a drug affects the body) and pharmacokinetics (how the body affects the drug), with changes in drug metabolism increasing the risks of toxicity and interactions.

For example, reduced rate of clearance of levothyroxine (a manufactured form of the thyroid hormone) from the body can result in increased risk of adverse consequences of overtreatment. Furthermore, weight loss, which is a phenotypic characteristic of frailty, can result in increased side effects of fat soluble drugs and is also associated with lower blood pressure, which can increase side effects, in particular falls, associated with some drugs.

Adverse drug reactions occurring particularly frequently and causing very significant risk in older people include falls, sedation, constipation, electrolyte disturbance and cognitive impairment, including delirium. Certain groups of drugs have been highlighted as particularly high risk in this respect.  These include:

  • Anticholinergics – drugs that block the action of acetylcholine, a chemical messenger that helps to send messages from your nerves to your muscles (risks include falls, cognitive decline, constipation)
  • Benzodiazepines – a class of psychoactive drugs used to treat insomnia and anxiety (risks include sedation, confusion, falls)
  • Diuretics – any substance that promotes increased production of urine or diuresis (risks include dehydration, constipation, falls)
  • Selective serotonin reuptake inhibitors (SSRIs) – a widely used type of antidepressant medication (risks include hyponatraemia or low sodium levels and delirium)
  • Antihypertensives – drugs used to treat high blood pressure (risks include falls)

It is important that clinicians can make prompt recognition of adverse drug reactions and therefore avoid mistaking the problem for a new medical condition, which can in turn lead to a ’prescribing cascade’ and increased risks from additional unnecessary treatment. For example, prescription of diuretics can lead to incontinence, which if mistaken for a new problem could lead to the prescriptions of an anticholinergic, which can in turn cause constipation and delirium, and so on, often ultimately resulting in falls and injury, which are the most common serious adverse consequence of polypharmacy.

Improving compliance and reducing risks of polypharmacy

Polypharmacy can also result in reduced efficacy due to poor compliance. There is evidence that in older people the likelihood of non-compliance rises in proportion to the number of drugs a person is prescribed and the complexity of the dosing regime.  This risks the loss of health benefits by poor adherence to important and necessary treatments. Furthermore, the cognitive decline which can often be an adverse consequence of polypharmacy can reduce the ability of a person with frailty to self care, which in turn increases the risk of both medication errors and of reduced efficacy due to poor adherence.

The risks of treatment conflicts and adverse consequences of polypharmacy for people with frailty are often compounded by poorly coordinated care, with multiple prescribers and inadequate medication reviews. However, these challenges can be addressed through the process of Comprehensive Geriatric Assessment (CGA).

CGA is clinically effective in improving the clinical management of older people with frailty, including medication optimization, by helping to prioritise problems and develop an individual person-centred care and treatment plan. Although the main aim of such medication reviews may be seen as in reducing medication (often termed ‘de-prescribing’) and simplifying treatment regimes, they also have an important role in identifying the absence of treatments which could have important clinical benefits, whether for an underlying condition, e.g. bone protection, or if indicated in association with other treatments, e.g. gastro-protection, in the presence of non steroidal anti-inflammatory drugs.

Tools are available to help determine the appropriateness of prescribing certain medications for older people. These tools can therefore assist in polypharmacy reviews for people with frailty. For example, Beers’ criteria focus upon drugs that should be avoided in older people. The Screening Tool for Older Persons Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) expand upon Beers’ criteria to build instruments which not only identify medications which are commonly inappropriately prescribed for older people, but also identify those which are commonly omitted even though they may offer clinical benefits.

However, although these individual tools can be helpful when reviewing polypharmacy for older people with frailty, they are not on their own sufficient to ensure a tailored individualised approach to treatment. In order to be most effective they must be used as part of a CGA to design holistic person centred treatment plan that must focus upon the preferences of the patient and their care givers, take into account findings from across all domains of the CGA and be appropriate and consistent with a person’s physical and mental capacities. Furthermore, because frailty is a dynamic condition, there must be a clear recognition of the need for an ongoing process of assessment and review, in order to adjust goals of treatment and care in alignment with each individual’s frailty trajectory.


Further information

2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

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NHS Wirral CCG STOPP START Tool to Support Medication Review

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Medicines optimisation: the safe and effective use of medicines to enable the best possible outcomes NICE Guidance (NG5)

Polypharmacy and medicines optimisation: Making it safe and sound – Kings Fund Report

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