Deprescribing: a 20-year retrospective

It has been 20 years since Michael Woodward wrote, as part of the ‘Geriatric Therapeutics’ series, the first article on deprescribing.¹ Since then, the term ‘deprescribing’ has become part of the medical lexicon, and by October 2023 more than 1000 articles had appeared in PubMed with ‘deprescribing’ in the title. While several definitions of deprescribing have appeared, at its heart it represents a process, supervised by a health professional and using a shared decision-making approach, for identifying and withdrawing (or dose reducing) medications which are not indicated or are ineffective or where potential harm outweighs potential benefit, with the aim of improving patient health.²

Numerous studies have documented the burden and ill-effects of inappropriate prescribing and polypharmacy, particularly among older, frail and multimorbid patients. The expectation that clinicians should adhere to various single-disease guidelines, derived from clinical trials involving mostly younger people, has led to an increase in exposure to polypharmacy. Older people, especially those who are frail, tend to experience lower efficacy of chronic medications and higher risk of adverse effects.³ Among people taking multiple medicines, many feel burdened by their treatment.⁴

In response to these observations, a plethora of deprescribing tools, protocols, guidelines and checklists have appeared to assist clinicians and patients in countering polypharmacy, treatment burden and medication-related harm.^{2, 5, 6} These aids can be broadly categorised as implicit or holistic approaches which consider all medications a patient is taking or more specific aids targeting high-risk medications, such as benzodiazepines, anticoagulants and oral hypoglycaemics.

In addition, ‘deprescribing networks’ have been established in various countries which comprise geriatricians, general physicians, primary care clinicians, clinical pharmacologists, pharmacists and other discipline representatives committed to researching and implementing ways of reducing inappropriate medication. The first deprescribing network was established in Australia in 2014.⁷ Subsequently, similar networks were established in the United States,⁸ Canada,⁹ England¹⁰ and Northern Europe.¹¹ These networks have been instrumental in producing and disseminating drug-specific, evidence-based deprescribing guidelines for clinicians, providing consumer-facing resources and support, developing national action plans for improving quality use of medications, promoting deprescribing research and convening national and international deprescribing conferences to share knowledge and forge collaborations.

Evidence has shown that deprescribing interventions can be feasibly conducted in a variety of clinical settings and can safely reduce the number of potentially inappropriate medications. Whether deprescribing prevents adverse drug events (ADEs), mortality or hospitalisations or improves mental and physical function and quality of life (QOL) has been harder to prove.¹² There are indications that direct, patient-focused interventions may reduce mortality, while some trials, but not all, have indicated favourable impacts on hospital admissions and QOL.¹³ More recent trials have focussed on using computer-generated medication advice or decision supports, some linked with electronic medical records, to encourage more consistent application of deprescribing in routine practice. Although reductions in potentially inappropriate medications were again seen, significant effects on other outcomes, including ADEs, deaths, hospital presentations, falls and QOL, have not materialised.¹² Why is that?

There are several possible reasons: the absolute reductions in the numbers of harmful medications were often very small (<0.5 medication per patient); uptake of deprescribing advice by prescribers was often no more than 50%; deprescribing interventions (reviewing medication lists, identifying candidate drugs for deprescribing, formulating and executing agreed deprescribing regimens with patients) were often limited to just one or two dedicated consultations; the effects of deprescribing certain drugs vary from person to person so that signals of benefit may be lost in aggregated data; hard endpoints such as deaths and ADEs are infrequent without long-term (>12 months) follow-up; and measures of function or QOL may be too insensitive to detect patient-important benefits. Also, for deprescribing to be successful, it must involve communication between and proactive engagement of the entire chain of multiple prescribers and pharmacists for individual patients; in addition, changes in illness trajectories necessitate timely revision of deprescribing regimens. In a world of time-pressured clinicians working in fragmented healthcare systems, it is perhaps not surprising that real-world clinical trials, contending with the aforementioned constraints, have failed to demonstrate consistent improvements in clinical outcomes.

Does this lack of proof render deprescribing efforts a waste of time? Certainly not. Patients still benefit from reducing medication burden, incur less out-of-pocket costs and are more likely, with fewer medications, to adhere to those that are essential for better health. Healthcare systems also benefit from the cost savings from the cessation of unnecessary medications, which can be redirected to better uses. With time, the full potential of deprescribing will be recognised as a result of better designed trials (including the much underrated n-of-1 trial); more precise identification of patient subgroups at greatest risk of medication harm and likely to benefit from deprescribing (including by means of artificial intelligence); more nuanced, whole-person deprescribing guidelines that include non-pharmacological substitutes; protected and scheduled time and linked remuneration for prescribers and pharmacists to conduct regular deprescribing reviews; fully connected electronic medical records for transferring medication-related information between multiple clinicians; and more empowered patients who question the necessity of their medications. When first prescribing a medication, determining the timing and circumstances for stopping will also help, as deprescribing is often not considered until problems emerge. Developing deprescribing resources for the growing number of patients with cognitive impairment and dementia constitutes another pressing challenge.

In the last 20 years, deprescribing has come to be recognised and embraced as a legitimate and important clinical practice for improving medication safety and patient health. The scale of polypharmacy and medication harm has been made clear, and deprescribing applied judiciously has proven safe. These observations alone argue for its systematic application in clinical practice, and in time one can reasonably predict that health benefits will become more apparent.

The author declares that he has no conflicts of interest.

No funding was received for this article.