One size fits all? How to optimize the prescribing of appropriate polypharmacy in chronic diseases, using a behavioral approach – a United Kingdom perspective

KEYWORDS:

• Prescribing
• polypharmacy
• multimorbidity
• Theoretical Domains Framework
• behavior change techniques
• intervention

1. Introduction

The use of medicines is the mainstay of chronic disease management. However, chronic disease management has now evolved into the management of more than one disease for many patients, which in turn, has led to the use of multiple medicines (sometime described as polypharmacy) to manage these chronic diseases. The concept of polypharmacy has also undergone an evolution in terms of definition (many of which have relied on numerical thresholds) and value judgments (should polypharmacy be considered negative or positive in terms of treatment). This editorial will explore these issues, and consider how polypharmacy can be optimized at a population and patient level, with a focus on behavior change as a means to achieve appropriate polypharmacy.

2. Polypharmacy: what it is and what it isn’t

Polypharmacy has usually been associated with the prescription and use of multiple drugs. There have been a variety of definitions employed which have used numerical thresholds to describe polypharmacy, such as four or more regularly prescribed medicines [1]. More recently, the term hyperpolypharmacy has also entered the literature, defined as 10 or more medicines [2]. Indeed, there has been the long-standing view that polypharmacy is a ‘bad thing’ and should be addressed by prescribers reducing the number of medicines being prescribed [2]. Studies have shown that the use of multiple medicines may expose patients to a higher risk of adverse events, hospitalizations and challenges with adherence [2]. Frail, older people are particularly susceptible to adverse effects of medicines due to changes in pharmacokinetics and pharmacodynamics which will affect clinical responses to medicines [3]. Indeed, further consideration needs to be given to the possibility of drug–drug interactions (some of which may be severe or life-threatening) which may occur as a result of prescribing of multiple medicines while attempting to manage multimorbidity [4]. An appreciation of which medicines act as inducers or inhibitors of other medicines is important when planning how best to prescribe for older people.

However, with increasing prevalence of multimorbidity (defined as the presence of two or more long-term conditions [5,6]), there is growing recognition that more medicines will be required to manage more medical conditions. Guidelines increasingly recognize that more than one medicine will be needed in the management of some long-term conditions, for example, diabetes. This is despite the fact that many trials will exclude older people with multimorbidity and polypharmacy, thereby creating an evidence vacuum [7]. Assessments of prescribing appropriateness should no longer focus on the number of medications prescribed and consider the presence of more than one condition in differentiating between ‘many’ medicines (appropriate polypharmacy) and ‘too many’ medicines (inappropriate polypharmacy [8]). ‘Appropriate polypharmacy’ acknowledges that patients may need and can benefit from many medications, provided that prescribing is evidence-based, avoids interactions and adverse events and reflects patients’ clinical conditions. In parallel, the addition of further medications to achieve appropriate polypharmacy needs to be carefully calibrated against adequate monitoring of disease control, with regular review by health-care professionals.

3. Evidence and guidance for appropriate polypharmacy

At a population level, research has shown that polypharmacy, when appropriate, can be beneficial for patients. One notable study linked electronic records from primary and secondary care in Scotland, and assessed the association between polypharmacy (defined as multiple medicines) and unplanned hospitalizations [9]. Admissions were more common in patients on multiple medications, but the risk for hospitalization varied according to the number of medical conditions. For patients with extensive multimorbidity (i.e. six or more conditions), patients taking four to six medications were no more likely to have unplanned admissions than those taking fewer medications (i.e one-three) [9]. According to the authors, this evidence suggested that polypharmacy based on a numerical threshold could no longer be considered as harmful. Recognition of the clinical context and the extent of multimorbidity needed to part of the decision-making on the use of medicines [9]. Thus, there should be a focus on appropriate prescribing and appropriate disease management. And this is the challenge for everyday practice. Recognition of the need for multiple medicines (while reducing the risk of adverse events) has been reflected in advice to health-care professionals. The United Kingdom (UK) National Institute for Health and Care Excellence (NICE) has issued guidance on the clinical assessment and management of multimorbidity [5]. The use of medicines featured prominently in the guidance, calling for review of medicines, consideration of medicines or non-pharmacological treatments that might be started as well as stopped, and discussion with the patient about approaches to disease management and the patient’s priorities for treatment (see later). A complementary publication from NICE, specifically about polypharmacy, has emphasized the difference between appropriate and problematic polypharmacy, the value of assessing the risks and benefits of individual treatments recommended in guidance for single health conditions and potential under-treatment in some conditions, for example, primary prevention of stroke and transient ischemic attack [10].

4. Interventions supporting prescribing of appropriate polypharmacy

Synthesis of trial findings has not found strong evidence as to what supports the prescribing of appropriate polypharmacy. A Cochrane review published in 2018 (and currently being updated) found little evidence on how to achieve appropriate polypharmacy and included studies reported little detail on the approach to intervention development and content [1]. A review of systematic reviews examining interventions addressing polypharmacy reported that interventions focusing on appropriate prescribing in the context of polypharmacy produced some benefits, but there was no consistent evidence on other outcomes, such as health-care utilization, morbidity, or mortality [11]. It is important to consider the impact of an intervention on outcomes that are important to patients, health-care providers and policymakers to ensure that assessed interventions can have the widest possible impact and which will allow for synthesis of similar studies to reinforce the strength of evidence [12].

5. How can we improve the prescribing of appropriate polypharmacy and will a ‘one-size-fits-all’ approach work?

Guidance produced by authoritative organizations, such as NICE, and outlined above have also strongly endorsed the role of partnership between prescriber and patient, recognizing a patient’s individual needs, preferences for treatment, health priorities, lifestyles, and goals [5]. Therefore, while guidance provides general principles to work to, individualization of treatment plans should be the goal. This suggests that a ‘one-size-fits-all’ approach will not be consistent with this guidance, and a different approach is needed which will require time and appropriate skills. Increasingly, decision-making of this nature, that is, prescribing, is being viewed through a behavioral lens, using the latter to help develop approaches to improve prescribing. Avorn [13] has highlighted the importance of the psychology behind decision-making, particularly the choices that are made about medicines in terms of prescribing of, and adherence to, medicines. Studies are now beginning to emerge which have focused on what drives decisions around the selection of medicines, and how decisions can be driven by changes in behavior. A program of work focusing on appropriate polypharmacy has used the Theoretical Domains Framework (TDF), which has been derived from 33 psychological theories that can help to identify barriers and facilitators to behavior change [14] in terms of prescribing polypharmacy and adherence to polypharmacy [15,16]. By identifying barriers and facilitators, it is then possible to link to strategies to overcome barriers or use the facilitators by applying behavior change techniques (BCTs) which can be embedded into an intervention. BCTs have been described as the ‘active ingredients’ of an intervention and are responsible for incurring behavior change [17]. An example of a BCT may be something like a prompt or cue which will remind an individual to perform a particular task, for example, an alert received on a mobile telephone as a reminder.

This program of work has developed an intervention that has focused on the prescribing of appropriate polypharmacy in older people in primary care, using a range of BCTs. The intervention, denoted as PolyPrime [18], is based around a short online video, targeting general practitioners (GPs). The intervention is delivered through the video (approximately 10 minutes in duration, equating to a typical consultation), which demonstrates how appropriate polypharmacy can be prescribed (i.e. the behavior) by a GP, through a simulated typical consultation with an older patient (played by an actor). The BCT being conveyed is ‘Modelling or demonstrating of behavior.’ The video also includes commentary from both the GP and patient emphasizing what they have gained professionally and personally from the consultation (BCT ‘Salience of consequences’). After viewing the video, GPs plan when and how they will ensure that target older patients are prescribed appropriate polypharmacy (BCT ‘Action planning’). They are reminded by practice staff to conduct such prescribing when these target patients present at the practice (BCT ‘Prompts/cues’) [18]. The intervention is currently undergoing pilot testing. The two main outcomes being assessed in this study are medication appropriateness, and health-related quality of life [12]. The selection of these outcomes has been informed by a core outcome set (COS) which has been defined as ‘an agreed or standardized set of outcomes that should be assessed and reported as a minimum for trial evaluations of similar interventions’ [19]. The PolyPrime pilot study will also conduct a cost analysis, based on the costs associated with the intervention, patients’ use of the health service and prescriptions. Other work which is focusing on interventions seeking to improve polypharmacy include the MultimorbiditY Collaborative Medication Review And Decision Making (MyComrade) study [20] and the Improving Medicines use in People with Polypharmacy in Primary Care (IMPP) study [21]. The MyComrade study is testing an evidence-based, theoretically informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care, and similar to PolyPrime, is based on aspects of behavior change. IMPP seeks to develop, implement, and evaluate an intervention to optimize medication use for patients with polypharmacy in a general practice setting. Medication review will be undertaken by GPs and pharmacists based in general practices. Both studies have yet to report findings.

6. Conclusions

Polypharmacy has been viewed as ‘one of the most pressing prescribing challenges’ [22] and it will continue to remain so as the population ages, and multimorbidity increases in incidence and prevalence. And medicines will continue to be the mainstay of management. Although there may be advances in formulations, such as the Polypill, which combine two or three medicines into a single dosage unit [23], prescribers and patients will still have to make decisions about getting the balance right between many (appropriate polypharmacy) or too many (inappropriate or problematic polypharmacy) medicines. Research needs to focus on developing interventions that will promote the prescribing of appropriate polypharmacy and support the individual requirements of prescribers and patients alike, thereby recognizing that one size will not fit all.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author wishes to acknowledge the support of the Dunhill Medical Trust (grant number: R298/0513) and the HSC R&D Division Cross-border Healthcare Intervention Trials in Ireland Network (CHITIN) programme, funded by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB) project reference CHI/5431/2018.