1 Introduction
The prescribing of multiple medicines, or polypharmacy, is increasingly common in clinical practice, particularly in older people (age ≥65 years) [
1‐
3]. This is likely owing to multiple factors including increasing life expectancy and the consequent growth in the prevalence of multimorbidity (i.e. the presence of two or more long-term conditions), as well as the enhanced availability of effective drug treatments and prescribing guidelines that advocate the use of more than one drug in the prevention and management of various health conditions [
4,
5].
Polypharmacy is often clinically indicated and beneficial in specific conditions (e.g. diabetes mellitus, hypertension) and patient populations (e.g. patients with multimorbidity). However, the use of multiple medicines poses medication safety risks to patients [
5,
6]. For example, a repeated cross-sectional analysis of community-dispensed prescribing data for 310,000 adults in Scotland found that the number of dispensed medications was the characteristic most strongly associated with potentially serious drug–drug interactions; 81 % of patients receiving ≥15 drugs were exposed to potentially serious interactions compared with 11 % of those dispensed two to four drugs [
5]. Drug interactions are a form of adverse drug event (ADE) that have been identified as a preventable cause of medication-related hospitalisations [
7,
8]. Balancing the clinical benefits and safety risks associated with the use of multiple medications is a difficult task; hence, polypharmacy has been described as one of the greatest prescribing challenges [
9].
This article outlines current perspectives on polypharmacy, makes the case for adopting the term ‘appropriate polypharmacy’ in ensuring patient safety, and outlines the inherent challenges for practice and research in doing so.
2 Polypharmacy: ‘Many’ Medicines or ‘Too Many’ Medicines?
One of the challenges in discussing polypharmacy and the associated medication safety implications is that the term itself currently lacks a universally accepted definition. Although we have referred to polypharmacy as the prescribing of multiple medicines, it is also commonly defined using a numerical threshold (e.g. co-prescribing of four or five medications) [
10,
11]. The term can also have a dual meaning [
12,
13]. For example, polypharmacy can refer to the prescribing of ‘many drugs’ or ‘too many’ drugs, the former being entirely appropriate [
12]. Polypharmacy has often been viewed negatively and seen to signify inappropriate drug therapy or ‘too many’ drugs [
12,
13]. Observational studies have highlighted the association between polypharmacy in older people and potentially inappropriate prescribing (PIP) [
14,
15], as well as negative clinical outcomes that pose risks to patients’ safety and well-being (e.g. ADEs, medication non-adherence) [
11]. Hence, interventions aimed at improving the appropriateness of prescribing for patients receiving polypharmacy have often focussed on reducing the number of prescribed medications [
16].
However, interventions that seek to solely reduce the number of prescribed medicines fail to consider inappropriate prescribing in its entirety. Inappropriate prescribing does not only encompass over-prescribing (prescribing of more drugs than clinically necessary) and mis-prescribing (incorrect prescribing of a necessary drug), it also includes under-prescribing (failure to prescribe a clinically indicated drug) [
17,
18]. Under-prescribing is common in older patients and the associated clinical consequences pose safety risks to patients (e.g. ischaemic stroke in patients undertreated for atrial fibrillation) [
19]. Polypharmacy has been associated with under-prescribing in older people [
20,
21]. For example, Kuijpers et al. [
20] showed that a significantly higher proportion of patients receiving polypharmacy (defined as four or more medicines) were under-treated (42.9 %) compared with those receiving fewer medicines (13.5 %). It has been speculated that fear of causing ADEs is contributing to under-prescribing by clinicians [
19] and this could partly account for the reported reluctance among clinicians to initiate new medications in patients receiving polypharmacy [
22].
Recent cohort studies using population datasets have challenged existing assumptions that polypharmacy is always hazardous, or indicative of poor care, and have highlighted the importance of considering the clinical context underlying prescribing [
23,
24]. For example, an analysis of Scottish primary care data linked to hospitalisations for a sample of approximately 180,000 adults showed that the strength of the association between the number of regular medicines and unplanned hospitalisations was greatly reduced when the number of clinical conditions was accounted for [
23]. As noted by Guthrie et al. [
5] polypharmacy is “potentially problematic rather than always inappropriate” and, as such, assessments of prescribing appropriateness need to extend beyond the number of drugs prescribed and consider co-existing medical conditions in differentiating between ‘many’ and ‘too many’ medicines.
Owing to the lack of a universally accepted definition, there have been calls to abandon the term polypharmacy in favour of terms such as ‘hyperpharmacotherapy’ or ‘polytherapy’ [
13,
25]. However, it is difficult to see this happening because of the term’s widespread use in the literature. Instead, an arguably better solution to this long-standing issue would be to follow Aronson’s recommendation and qualify the term as either appropriate or inappropriate [
12]. A recent report published by the King’s Fund in the UK has promoted the term ‘appropriate polypharmacy’, described as ‘prescribing for an individual with complex or multiple conditions where medicine use has been optimised and prescribing is in accordance with best evidence’, rather than existing thresholds that define polypharmacy based on the number of prescribed medications [
26]. The concept of ‘appropriate polypharmacy’ recognises that patients can benefit from multiple medications provided that prescribing is evidence based and reflects patients’ clinical needs. Greater use of this term may help to dispel existing misconceptions that polypharmacy signifies ‘too many’ medicines and reduce reluctance among clinicians to initiate necessary medicines in patients already receiving polypharmacy.
4 Recommendations for Future Clinical Practice and Research
In ensuring the prescribing of appropriate polypharmacy, researchers and clinicians need to maintain a broad focus. The challenges posed by the prescribing of polypharmacy are neither limited to the older population nor the prescribing of ‘too many’ drugs. In the absence of a universally applicable, valid and reliable measure of appropriate polypharmacy, future assessments of prescribing appropriateness should assess both under-prescribing and over-prescribing across all adult populations using validated tools as surrogate markers (e.g. STOPP/START [
51], PROMPT [
37]). Medication regimen complexity should also be considered to reduce factors other than the absolute number of medications that contribute to the overall treatment burden (e.g. dosing frequency). This could ultimately enhance medication adherence.
Efforts to optimise polypharmacy should adopt a patient-centred approach as advocated by recent guidance [
33,
34]. It is important to recognise that appropriate polypharmacy is not a fixed end-point but rather an ideal concept. The threshold that differentiates between the prescribing of ‘many’ drugs and ‘too many’ drugs will not only vary according to individual patient’s clinical conditions, but also over time. For example, as multimorbid patients age and become frail, preventive medications become less meaningful, and clinicians must establish when it is appropriate to transition from disease-modifying treatment to a palliative approach, whereby medications are reduced or discontinued [
26]. Accordingly, regular medication reviews will serve an increasingly important function in ensuring appropriate prescribing according to patients’ existing clinical conditions and life expectancy.
In the absence of a universal indicator with suitable sensitivity and specificity for identifying patients receiving inappropriate polypharmacy, it may be better to focus on specific drug classes that pose safety risks. Researchers and clinicians can draw from the existing body of observational research on PIP to identify suitable target drug classes.
Finally, more attention needs to be paid to the clinical outcomes associated with appropriate polypharmacy. A Cochrane review of interventions to improve appropriate polypharmacy in older people highlighted that assessments of clinically relevant outcomes (e.g. quality of life) have been lacking in trials to date and, where assessed, findings have often been inconsistent or difficult to compare because of heterogeneity in measurement scales [
10]. Increasing emphasis is being placed on the importance of ‘core outcome sets’ (COS) as an agreed and standardised set of outcomes that should be measured and reported, as a minimum, in all trials in a specific clinical area [
52]. COS are intended to ensure that selected outcomes are relevant to key stakeholders and to overcome problems with heterogeneity in outcome measurements that have hindered the pooling of data in systematic reviews. Ongoing work as part of the COMET (Core Outcome Measures in Effectiveness Trials) initiative is seeking to establish rigorous methods for developing COS [
52,
53] and future research should focus on developing a COS for trials of interventions aimed at improving appropriate polypharmacy.
5 Conclusion
In current clinical practice where the prescribing of multiple medicines is increasingly common in adults with multimorbidity and advanced age, differentiating between ‘many’ drugs and ‘too many’ drugs is proving ever more complex. Previous assumptions that polypharmacy is synonymous with ‘too many’ medicines or inappropriate prescribing have been undermined because when patients’ clinical context is taken into consideration, the prescribing of ‘many’ medicines can, in fact, be entirely appropriate. Conceptualising polypharmacy as a numerical threshold is unhelpful because it fails to consider that the appropriate number of medicines varies according to individual patients’ clinical needs and may overlook the omission of potentially beneficial medications, which can equally pose risks to patients’ safety and well-being. We contend that, as a stand-alone term, polypharmacy should be interpreted as the prescribing of multiple medicines and, rather than quantifying the term according to the number of prescribed medicines, greater emphasis should be placed on qualifying the term based on the clinical appropriateness of the combination of medicines for the individual patient. Increased use of the term ‘appropriate polypharmacy’ could encourage greater consideration of the clinical context underlying prescribing, as well as increased acceptance that the prescribing of multiple medicines is ‘potentially problematic rather than always inappropriate’.
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