Evidence-Based Deprescribing: Reversing the Tide of Potentially Inappropriate Polypharmacy

Direct Deprescribing Targeting All Medicines

The evidence base for direct patient-level deprescribing that assesses all medicines, not just specific medicine classes, features several high-quality observational studies and controlled trials, and subgroup findings from a recent comprehensive systematic review. In this review of 132 studies, which included 56 randomized controlled trials [47], mortality was shown in randomized trials to be decreased by 38% as a result of direct (ie, patient-level) deprescribing interventions. However, this effect was not seen in studies of indirect deprescribing comprising mainly generic educational interventions. While space prevents a detailed analysis of all relevant trials, some of the more commonly cited sentinel studies are mentioned here.

In a controlled trial involving 190 patients in aged care facilities, a structured approach to deprescribing (Good Palliative–Geriatric Practice algorithm) resulted in 63% of patients having, on average, 2.8 medicines per patient discontinued, and was associated with a halving in both annual mortality and referrals to acute care hospitals [48]. In another prospective uncontrolled study, the same approach applied to a cohort of 70 community-dwelling older patients resulted in an average of 4.4 medicines prescribed to 64 patients being recommended for discontinuation, of which 81% were successfully discontinued, with 88% of patients reporting global improvements in health [49]. In a prospective cohort study of 50 older hospitalized patients receiving a median of 10 regular medicines on admission, a formal deprescribing process led to the cessation of just over 1 in 3 medicines by discharge, representing 4 fewer medicines per patient [50]. During a median follow-up period of just over 2.5 months for 39 patients, less than 5% of ceased medicines were recommenced in 3 patients for relapsing symptoms, with no deaths or acute presentations to hospital attributable to cessation of medicines. A multidisciplinary hospital clinic for older patients over a 3-month period achieved cessation of 22% of medicines in 17 patients without ill effect [51].

Two randomized studies used the Screening Tool of Older People’s Prescriptions (STOPP) to reduce the use of PIMs in older hospital inpatients [52,53]. One reported significantly reduced PIMs use in the intervention group at discharge and 6 months post-discharge, no change in the rate of hospital readmission, and non-significant reductions in falls, all cause-mortality, and primary care visits during the 6-month follow-up period [52]. The second study reported reduced PIMs use in the intervention group of frail older patients on discharge, although the proportion of people prescribed at least 1 PIM was not altered [53].

Recently, a randomized trial of a deprescribing intervention applied to aged care residents resulted in successful discontinuation of 207 (59%) of 348 medicines targeted for deprescribing, and a mean reduction of 2 medicines per patient at 12 months compared to none in controls, with no differences in mortality or hospital admissions [54]. The evidence for direct deprescribing is limited by relatively few high-quality randomized trials, small patient samples, short duration of follow-up, selection of specific subsets of patients, and the absence of comprehensive re-prescribing data and clinical outcomes.

Methods Used for Direct Deprescribing

At the level of individual patient care, various instruments have been developed to assist the deprescribing process. Screening tools or criteria such as the Beers criteria and STOPP tool help identify medicines more likely than not to be inappropriate for a given set of circumstances and are widely used by research pharmacists. Deprescribing guidelines directed at particular medications (or drug classes) [55], or specific patient populations [56], can identify clinical scenarios where a particular drug is likely to be inappropriate, and how to safely wean or discontinue it.

In applying a more nuanced, patient-centered approach to deprescribing, structured guides comprising algorithms, flowcharts, or tables describe sequential steps in deciding which medications used by an individual patient should be targeted for discontinuation after due attention to all relevant factors. Such guides prompt a more systematic appraisal of all medications being used. In a recent review of 7 structured guides that had undergone some form of efficacy testing [59], the strongest evidence of efficacy and clinician acceptability was seen for the Good Palliative–Geriatric Practice algorithm [48] (Figure) and the CEASE protocol [29,30,50,60] (Table). Both have been subject to a process of development and refinement over months to years involving multiple clinician prescribers and pharmacists. 

Clinical Circumstances Conducive to Deprescribing

Deprescribing should be especially considered in any older patient presenting with a new symptom or clinical syndrome suggestive of adverse medicine effects. The advent of advanced or end-stage disease, terminal illness, dementia, extreme frailty, or full dependence on others for all cares marks a stage of a person’s life when limited life expectancy and changed goals of care call for a re-appraisal of the benefits of current medicines. Lack of response in controlling symptoms despite optimal adherence and dosing or conversely the absence of symptoms for long periods of time should challenge the need for ongoing regular use of medicines. Similarly, the lack of verification, or indeed repudiation, of past diagnostic labels which gave rise to indications for medicines in the first place should prompt consideration of discontinuation. Patients receiving single medicines or combinations of medicines, both of which are high risk, should attract attention [63], as should use of preventive medicines for scenarios associated with no increased disease risk despite medicine cessation (eg, ceasing alendronate after 5 years of treatment results in no increase in osteoporotic fracture risk over the ensuing 5 years [64]; ceasing statins for primary prevention after a prolonged period results in no increase in cardiovascular events 8 years after discontinuation [65]). Evidence that has emerged that strongly contradicts previously held beliefs as to the indications for certain medicines (eg, aspirin as primary prevention of cardiovascular disease) should lead to a higher frequency of their discontinuation. Finally, medicines which impose demands on patients which they deem intolerable in terms of dietary and lifestyle restrictions, adverse side effects, medicine monitoring (such as warfarin), financial cost, or any other reason likely to result in nonadherence, should be considered candidates for deprescribing [25].