Deprescribing: What do we know, and where to next?

Abstract

Deprescribing has been defined as the process of identifying and discontinuing medications in which existing or potential harms outweigh potential benefits within the context of an individual patient's care goals, function, values and preferences.1 Internationally, there has been an increasing recognition of the need for progressing research into deprescribing due to the high prevalence of unnecessary polypharmacy (multiple medication use) and known medication-related harms. The need to fill these knowledge gaps has been identified by the formation of the Australian Deprescribing Network (ADeN) in 2015,1 and subsequently by the Canadian Deprescribing Network2 and more recently by the English Deprescribing Network,3 and the US4 and Northern European Deprescribing Research Networks. Deprescribing networks are typically comprised of multidisciplinary groups of clinicians, academic researchers, policymakers and consumer representatives, which will be essential to facilitate translation of deprescribing into clinical practice. Deprescribing has been featured extensively in the British Journal of Clinical Pharmacology5-10 with a number of imperative reviews covering various areas of research. Two recent systematic reviews have focused on a specific patient population, namely people with limited life expectancy.8, 10 Lundby and colleagues8 reviewed the attitudes of healthcare professionals towards deprescribing in people with limited life expectancy, outlining the significance of four themes: “(i) patient and relative involvement; (ii) the importance of teamwork; (iii) health care professionals' self-assurance and skills; and (iv) the impact of organizational factors.” Whilst Shrestha et al.10 found that deprescribing interventions in people with a limited life expectancy (or life-limiting illness) were effective at improving medication appropriateness, but further research is required into the clinical outcomes and cost-effectiveness. While more research is being conducted with a focus on deprescribing, we have also seen methodological challenges in this new field. Defining “deprescribing” has been an ongoing discussion, for example, whether dose reduction is part of deprescribing. A systematic review of deprescribing definitions published in 20156 found that the majority of definitions in the literature to date used terms related to discontinuation (e.g. stop, cease, withdraw), while a limited number also included dose reduction, substitution and tapering. Two more recent papers have discussed the broader concept of deprescribing in order to advance the research in this field.11, 12 While it can be important to capture both the outcomes of medication cessation and dose reduction in deprescribing trials, the chosen outcome may depend on the clinical question and patient group studied as well as the setting and drug/drug classes targeted. Given the lack of a consistent definition, future studies should clinically justify the chosen outcome and include details of how the outcome was defined so that the success, benefits and potential harms of deprescribing trials can be appropriately represented and summarised in future work. Furthermore, given that doctors and patients often decide to stop a medication in clinical practice, knowledge of the potential harms and benefits of deprescribing is vital to inform clinical decisions and health service research. A 2015 systematic review concluded that deprescribing is feasible, likely safe and may lead to better clinical outcomes such as reduced mortality.13 However, another methodological limitation in this field is that studies aiming to capture the potential benefits and harms of deprescribing can vary widely in their design. Moving forward, it may be useful to distinguish deprescribing studies into ‘medication cessation’ vs ‘deprescribing intervention’ trials. Medication cessation trials are those where deprescribing/medication cessation is attempted in all participants in the intervention group. These trials (which generally target a single drug/drug class) provide direct information about the clinical benefits and harms of deprescribing in the target population. Deprescribing intervention trials, on the other hand, are where an intervention (such as an educational intervention or medication reviews) is applied to a participant group which aims to increase, but does not require, deprescribing. These studies are typically focused on the success of the intervention, and therefore primary outcomes may be the proportion of participants who stopped a medication. In addition, clinical outcomes are also often captured, but are likely reliant on the success of the intervention in achieving deprescribing as well as the characteristics of those who did deprescribe, and any unintended consequences or benefits of the intervention that were not a direct result of deprescribing. While both types of studies are clearly important and can provide information about the safety and benefits of deprescribing, the results of these studies may not be directly comparable. Future work is required to develop a taxonomy of studies to enable better comparison of interventional deprescribing studies. Another important area of research is understanding enablers and barriers to implementing deprescribing into clinical practice. The involvement and empowerment of consumers in the deprescribing process has been highlighted by two reviews published in British Journal of Clinical Pharmacology, the first describing a patient-centred process for deprescribing in practice6 and the second an environmental scan of patient educational materials for deprescribing.9 Fajardo et al. identified 48 patient educational materials for deprescribing; however, significant limitations of the available materials were identified, including unbalanced presentation of potential harms and benefits, above average reading levels, and lack of materials targeting preventative medications.9 Moreover, qualitative research has been essential in increasing our knowledge of the potential barriers to and enablers of deprescribing in practice. Barriers may exist at the patient/public, healthcare provider, healthcare organisation and broader environment (policy, government, regulatory) level and are likely to be intertwined.14 Moving on from this knowledge to the development, feasibility, implementation and sustainability of interventions to increase deprescribing in practice is a future research focus in this field. Use of theory and learning from the behavioural science7 and the implementation and de-implementation science fields may help enable understanding the success of previous deprescribing intervention trials and planning for future research. For example, the systematic review by Hansen and colleagues7 applied the Behavioural Change Techniques (BCT) taxonomy to previously conducted deprescribing studies to examine which components of interventions were effective in reducing inappropriate medication use. They found that combinations of a range of BCTs were effective; however, significant heterogeneity in the studies impeded any strong conclusions. Lastly, collective international efforts are needed to inform evidence on the safety and efficacy of medication withdrawal and economics of deprescribing across health care settings, and to establish systems to educate multidisciplinary health professionals at all stages of training to deprescribe. Danijela Gnjidic is funded by the Australian National Health and Medical Research Council (NHMRC) Dementia Leadership Fellow. Emily Reeve is supported by a National Health and Medical Research Council (NHMRC)-Australian Research Council (ARC) Dementia Research Development Fellowship. There are no competing interests to declare.

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