Deprescribing in the Older Patient: A Narrative Review of Challenges and Solutions

Figures & data

Table 1 Summary of Systematic Reviews Examining Safety and Efficacy of Deprescribing Interventions

Citation	Study Population	Deprescribing Target	Number and Type of Studies	Impact on Medication Use*	Impact on Global Health Outcomes (Mortality, Hospitalization, Geriatric Syndromes)*	Adverse Drug Withdrawal Effects*
Cardona et al 2021^Citation74	Palliative care patients aged ≥ 65 years in hospital setting.	Most studies focused on general deprescribing.	5 RCTs, 1 retrospective non-RCT, 1 prospective non-RCT.	Hospital-initiated multi-component, multidisciplinary deprescribing interventions reduced PIMs.	No evidence of reduction in long-term mortality and hospitalization.	3 studies reported no difference between deprescribing intervention and control groups in adverse drug withdrawal effects after 2–3 months.
Bloomfield et al 2020^Citation52	Community-dwelling older adults aged ≥ 65 years.	Most studies focused on general deprescribing.	12 RCTs and 26 cluster randomized controlled trials.	9/13 studies showed a reduction in PIMs.	Meta-analysis of RCTs showed comprehensive medication review resulted in a 26% relative risk reduction (OR 0.74; 95% CI: 0.58–0.95) or 1.4% absolute reduction in all-cause mortality, but no significant effect on hospitalization (RR 1.07; 95% CI: 0.92–1.26). Most RCTs showed no significant improvement in falls or health-related quality of life.	NR
Kua et al 2019^Citation75	Nursing home residents aged ≥ 60 years.	Most studies focused on general deprescribing.	30 RCTs	Meta-analysis of RCTs showed deprescribing interventions significantly reduced the number of people with PIMs by 59% (OR 0.41; 95% CI: 0.19–0.89).	Meta-analysis of RCTs showed deprescribing was effective in reducing all-cause mortality (OR 0.90; 95% CI: 0.82–0.99) but not falls (OR 0.85; 95% CI: 0.73–1.00) and hospitalization (OR 0.72; 95% CI: 0.31–1.66). Subgroup analysis showed deprescribing interventions involving structured medication review by healthcare professionals were associated with a reduction in all-cause mortality (OR 0.74; 95% CI: 0.65–0.84), and falls (OR 0.76; 95% CI: 0.62–0.93).	NR
Ulley et al 2019^Citation43	Community-dwelling older adults aged ≥ 65 years.	Most studies focused on general deprescribing.	12 RCTs, 1 non-RCT, 9 cross-sectional studies.	4/22 deprescribing intervention studies showed an overall reduction in number of medications.	13/22 deprescribing intervention studies reported improved adherence. However, there is insufficient evidence to conclude that deprescribing interventions routinely improve medication adherence in community-dwelling older adults.	NR
Shrestha et al 2019^Citation76	Older patients aged ≥ 65 years with life-limiting illness and limited life expectancy in hospital and RACF.	Most studies focused on general deprescribing.	3 RCTs and 6 non-RCTs.	Deprescribing interventions reduced PIMs in older patients with life-limiting illness and limited life expectancy.	Impact of deprescribing intervention on mortality, quality of life, falls, physical and cognitive function remain unclear. One non-RCT study reported a significant decrease in mortality at 12 months.	NR
Nakham et al 2019^Citation77	Older adults aged ≥ 65 years in community, hospital, nursing home settings.	Anti-cholinergics	4 RCTs and 4 non-RCTs.	2 of 4 RCTs and all non-RCT studies reported a decrease in anticholinergic burden following deprescribing interventions.	Only 1 RCT reported clinical outcome (cognitive function), and showed no statistically significant difference between deprescribing interventions and control group.	NR
Thillainadesan et al 2018^Citation78	Older adults with a median age of ≥ 65 years in hospital setting.	Most studies focused on general deprescribing.	9 RCTs	Deprescribing interventions in hospital setting were safe and effective at reducing PIM.	Impact on clinical outcomes such as mortality, quality of life, falls and hospitalization was uncertain.	NR
Wilsdon et al 2017^Citation79	Older adults aged ≥ 65 years in community and hospital settings.	7 studies focused on PPI deprescribing, 14 studies focused on general deprescribing.	6 RCTs and 15 non-RCTs	6 of 21 studies demonstrated effective deprescribing interventions, 11 were inconclusive, 4 were ineffective. Types of effective deprescribing interventions included geriatrician-led deprescribing, academic detailing for GPs, population-wide education and promotion strategy.	No clear evidence that PPI deprescribing translates into better clinical outcomes in older people.	NR
Reeve et al 2017^Citation80	Older adults aged ≥ 65 years in community, hospital and nursing home settings.	Benzodiazepines or Z-drugs	5 RCTs and 2 non-RCTs	RCTs and non-RCTs showed deprescribing of benzodiazepine and Z-drugs was feasible in older people. However, the benefits and sustainability of these interventions are unclear.	NR	Most RCTs and non-RCTs studies showed no difference in prevalence of withdrawal symptoms or sleep quality.
Page et al 2016^Citation22	Older adults aged ≥ 65 years in community, hospital and nursing home settings.	General deprescribing and single medications.	56 RCTs and 60 non-RCTs	Meta-analysis of RCTs showed deprescribing reduced both total number of medications (MD −0.99; 95% CI: −1.83 to −0.14) and PIMs (MD-0.49; 95% CI: −0.70 to −0.28).	Meta-analysis of non-RCTs showed deprescribing polypharmacy (≥3 medications) were associated with a significant reduction in mortality (OR 0.32; 95% CI: 0.17–0.60). However, meta-analysis of RCTs showed deprescribing polypharmacy (≥3 medications) had no statistically significant mortality benefit (OR 0.82; 95% CI: 0.61–1.11) and no significant change in risk of falls (OR 0.65; 95% CI: 0.40–1.05) or quality of life measures. Deprescribing of single medication class was not associated with a significant difference in mortality and quality of life measures in both RCTs and non-RCTs.	RCTs showed deprescribing interventions were not associated with a significant increase in adverse drug withdrawal events.
Johansson et al 2016^Citation81	Older adults aged ≥ 65 years in community, hospital and nursing home settings.	General deprescribing	21 RCTs and 4 non-RCTs	3 RCTs showed deprescribing interventions reduced total number of medications compared to controls.	Meta-analysis of pooled data from RCTs and non-RCTs showed deprescribing strategies had no effect on all-cause mortality (OR 1.02; 95% CI: 0.84–1.23). There was no convincing evidence from RCTs and non-RCTs that deprescribing was effective in improving clinical outcomes (hospitalization and mortality).	NR

Notes: * Specific numerical data in the forms of odds ratio (OR), risk ratio (RR) or mean difference (MD) and 95% confidence interval are only reported if the study has performed meta-analyses of the outcomes of interest.

Abbreviations: GPs, general practitioners; CI, confidence intervals; NR, not reported; OR, odds ratio; PIMs, potentially inappropriate medications; PPI, proton pump inhibitor; RACF, residential aged care facility; RCTs, randomized controlled trials.

Table 2 Summary of Challenges of Existing Deprescribing Research and Potential Solutions for Future Studies

	Challenges	Potential Solutions
Patients	Assessing deprescribing outcomes based on clinician preferences.^Citation24,Citation25	Involving patients in all phases of research including defining relevant outcomes, using patient reported outcome measures, and using individualized goal attainment scale outcomes.^Citation21,Citation24
	Unclear how to best educate patients about deprescribing.^Citation22	Exploring the acceptability and effectiveness of different educational programs on deprescribing and how to best tailor these to different patient populations such as patients with different levels of health literacy.^Citation22
Healthcare Professionals	Data on clinical outcomes
	Lack of sufficiently powered RCTs assessing long-term deprescribing benefits, safety and sustainability.^Citation22^–^Citation24,Citation28 Existing studies assessing outcomes such as the feasibility of deprescribing or reduction in the medicines count instead of clinical outcomes.^Citation22^–^Citation25	Large RCTs with long-term follow-up assessing prescribing and clinical outcomes and outlining the deprescribing protocols used.^Citation22^–^Citation25,Citation28
	Detail reported in methods of exiting studies
	Deprescribing schedule not explicitly reported.^Citation22 Management of patients during deprescribing such as withdrawal symptoms not outlined.^Citation25	Practical guidance regarding appropriate management during deprescribing, including providing safer alternatives such as nonpharmacological therapy.^Citation25
	Generalizability to Clinical Practice
	Range of drug classes seen in clinical practice not explored for deprescribing.^Citation22 Not specifying comorbidities and concurrent medications and not accounting for these potential confounders.^Citation26,Citation29,Citation30 Excluding patient populations such as palliative care.^Citation20,Citation30	Deprescribing different drug classes seen in practice, in different patient populations and explicitly specifying characteristics such as frailty, comorbidities and concurrent medications, adjusting for any potential confounders.^Citation20,Citation22,Citation29,Citation30,Citation82
Health Organizations	Large, robust studies assessing cost-effectiveness of deprescribing interventions, including models of care with time specifically dedicated to deprescribing are limited.^Citation25,Citation28 Healthcare organizations undertake deprescribing research as separate groups nationally and internationally.^Citation25	More studies exploring cost-effectiveness of different deprescribing interventions, including models of care with dedicated time for deprescribing.^Citation25 Collaboration between different healthcare organizations to increase capacity to undertake large deprescribing trials.
	Electronic healthcare systems do not always include deprescribing prompts embedded into them.^Citation31,Citation32	Exploring deprescribing interventions embedded into electronic healthcare management systems.^Citation31,Citation32
	Studies exploring specific roles of different healthcare disciplines during the deprescribing process are limited.^Citation28	More research to understand specific roles of different health disciplines which may help develop streamlined, efficient processes around deprescribing.^Citation28

Figure 1 Deprescribing challenges and their solutions across different levels of healthcare system, informed by multiple sources.^36,38

Abbreviations: CCDSS, Computerized Clinical Decision Support Systems; QIs, Quality Indicators

Table 3 Summary of Challenges and Solutions of Implementing Deprescribing in the Healthcare System, Data from Multiple Sources^36,38

	Challenges	Solutions
Patients	Poor health literacy, reluctant to discontinue medications due to false belief. Patients are often passive recipients of medications, not involved in the decision making process on the use of medications.	Provide educational materials and tools (eg patient-held medication record, medication passport) to enhance patient awareness about inappropriate polypharmacy and understand the benefits and harms of each medication. Engage and empower patients to play an active role in their health care, so they can safely manage their own medications.
Healthcare Professionals	Increasing number of complex geriatric patients with multimorbidity. Lack of formal training in prescribing for older patients with complex polypharmacy. Time constraints to counsel patients on medication-related harms.	Provide health professionals with tools, guidelines and educational resources on how to manage polypharmacy in older people. Develop educational curricula on safe medication management and deprescribing for both undergraduate and postgraduate health professionals. Provide additional incentives to health professionals that conduct a medication regimen review as part of routine health check-up.
Health Organizations	Healthcare systems and practices of medication are often complex and dysfunctional. Fragmentation of care within healthcare system. Poor coordination and communication between different health professionals (eg specialists and general practitioners) when new medications are initiated.	Integrate health services across all levels of healthcare systems to provide multidisciplinary patient-centered care. Establish a national deprescribing working group of leading experts, regulators and policymakers to develop strategies, guidelines and action plans on polypharmacy and deprescribing in older people.

Table 4 Summary of Systematic Reviews to Evaluate Computerized Clinical Decision Support Systems (CCDSS) in Deprescribing in Older Adults

Citation	Study Population	Deprescribing Target	Number and Type of Studies	Impact on Medication Use*	Impact on Global Health Outcomes (Mortality, Hospitalization, Geriatric Syndromes)*	Adverse Drug Withdrawal Effects*
Bloomfield et al 2020^Citation52	Community-dwelling older adults aged ≥ 65 years.	Most studies focused on general deprescribing.	4 RCTs	2 studies reported reduction in PIMs in the intervention group, and 2 reported no effect.	NR	NR
Monteiro et al 2019^Citation51	Older adults aged ≥ 65 years in community and hospital settings.	General deprescribing and single medications.	10 RCTs and 6 non-RCTs	CCDSS may reduce PIMs.	NR	NR
Dalton et al 2018^Citation53	Older adults aged ≥ 65 years in hospital setting.	General deprescribing and single medications.	2 RCTs and 6 non-RCTs	Intervention patients were less likely to be prescribed a PIM (OR 0.6; 95% CI: 0.38 −0.93)	Most studies did not assess global health outcomes such as falls, hospitalization or mortality. One non-RCT study showed CCDSS resulted in a statistically significant reduction in inpatient falls.	NR
Iankowitz et al 2012^Citation54	Older adults aged ≥ 65 years in community and hospital settings.	General deprescribing and single medications.	4 RCTs and 1 non-RCTs	CCDSS had the potential for decreasing the number of PIMs, conclusions about unplanned hospitalizations could not be made. The computer systems were significantly effective in decreasing frequency of ordering PIMs.	NR	NR

Notes: * Specific numerical data in the forms of odds ratio (OR), risk ratio (RR) or mean difference (MD) and 95% confidence interval are only reported if the study has performed meta-analyses of the outcomes of interest.

Abbreviations: RCT, randomized controlled trial; c-RCT, cluster randomized controlled trial; CCDSS, computerized clinical decision support systems; NR, not reported; PIMs, potentially inappropriate medications; OR, odds ratio; CI, confidence intervals.

Table 5 New South Wales Therapeutic Advisory Group (NSW TAG) Polypharmacy Quality Use of Medicines (QUM) Indicators⁸³

Identification of Older Patients at High Risk of Medication-Related Harm
1. Percentage of older patients that are appropriately assessed for risk of harm from inappropriate polypharmacy 2. Percentage of older patients that are appropriately assessed for risk of medication-related falls 3. Percentage of older patients that are appropriately assessed for risk of medication-related impairment of cognitive and/or physical function
Intervention: a hospital-based medication review (HBMR)
4. Percentage of older patients at high risk of medication-related harms that receive a hospital-based medication review and, if applicable, a deprescribing plan
Optimising discharge communications and continuation of medication care at transitions of care
5. Percentage of older patients at high risk of medication-related harms with a recommendation for a post-discharge medication review, when hospital-based medication review is not performed 6. Percentage of older patients whose discharge summaries contain a current, accurate and comprehensive list of medicines, including explanations for any medication therapy changes and, if applicable, details of a deprescribing plan 7. Percentage of older patients who receive a current, accurate and comprehensive medication list, including explanations for any medication changes and, if applicable, details of a deprescribing plan, at the time of hospital discharge

Notes: Reproduced with permission from New South Wales Therapeutic Advisory Group (NSW TAG) Polypharmacy Quality Use of Medicines (QUM) Indicators. Available from: https://www.nswtag.org.au/qum-indicators/ Accessed May 6, 2021. © NSW Therapeutic Advisory Group Inc 2020.⁸³

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