Deprescribing in Older Adults

STATE OF THE ART REVIEW
Deprescribing in older adults with polypharmacy
BMJ: first published as 10.1136/bmj-2023-074892 on 7 May 2024. Downloaded from http://www.bmj.com/ on 7 May 2024 by guest. Protected by copyright.
Anna Hung,1,2,3,* Yoon Hie Kim,4,* Juliessa M Pavon4,5
A B S T RAC T
1
Department of Population
Polypharmacy is common in older adults and is associated with adverse drug events,
Health Sciences, Duke University cognitive and functional impairment, increased healthcare costs, and increased risk
School of Medicine, Durham,
NC, USA of frailty, falls, hospitalizations, and mortality. Many barriers exist to deprescribing,
but increased efforts have been made to develop and implement deprescribing
2
Duke-Margolis Center for
Health Policy, Durham, NC, USA
3
Center of Innovation to interventions that overcome them. This narrative review describes intervention
Accelerate Discovery and
Practice Transformation, Durham components and summarizes findings from published randomized controlled trials
VA Health Care System, Durham,
NC, USA
that have tested deprescribing interventions in older adults with polypharmacy, as well
4
Division of Geriatrics, as reports on ongoing trials, guidelines, and resources that can be used to facilitate
Department of Medicine, Duke
University School of Medicine, deprescribing. Most interventions were medication reviews in primary care settings, and
Durham, NC, USA
5
many contained components such as shared decision making and/or a focus on patient
Geriatrics Research, Education,
and Clinical Center (GRECC) care priorities, training for healthcare professionals, patient facing education materials,
Durham VA Health Care System,
Durham, NC, USA and involvement of family members, representing great heterogeneity in interventions
*
Co-first authors addressing polypharmacy in older adults. Just over half of study interventions were
Correspondence to: A Hung
anna.hung@duke.edu found to perform better than usual care in at least one of their primary outcomes, and
Cite this as: BMJ 2024;385:e074892 most study interventions were assessed over 12 months or less.
http://dx.doi.org/10.1136/
bmj‑2023‑074892
Series explanation: State of the
Art Reviews are commissioned Introduction care goals, functional status, life expectancy, values,
on the basis of their relevance Polypharmacy, commonly defined as taking at and preferences.”14 This process is often supervised
to academics and specialists
in the US and internationally.
least five drug treatments, is common in older by a healthcare professional, but shared decision
For this reason they are written populations.1 2 The prevalence of this condition, making is critical, because deprescribing decisions
predominantly by US authors. when combined across multiple countries, is about need to consider patient and care partner values
45% in older populations (those aged 65 years or and preferences.15 16 Contrary to a simplistic goal
older) compared with 27% in younger populations of reducing the number of drug treatments, the
(those aged under 65 years).1 Although older adults essence of deprescribing lies in achieving a nuanced
are more likely to have multiple chronic conditions, balance: acknowledging the concept of “appropriate
and guidelines often recommend multiple drug polypharmacy.”17 18 This approach recognizes that
treatments, studies have found that polypharmacy certain medical conditions can warrant the use
can lead to problems such as adverse drug events, of multiple drug treatments to effectively manage
drug–drug interactions, drug treatment non- symptoms, prevent complications, and improve
adherence,3 4 cognitive and functional impairment,5 overall patient wellbeing. Deprescribing, in this
and increased risk of frailty, disability, falls, context, seeks not to diminish the drug treatment
hospitalizations, and mortality.6-8 count arbitrarily, but rather to ensure judicious and
Polypharmacy is also associated with the use of contextually appropriate drug treatment use.
potentially inappropriate medications,9 10 which is Coined in 2003, the term “deprescribing” has
linked to increased risk of hospitalization and visits to witnessed significant growth in usage, research,
the emergency room.11 Furthermore, polypharmacy and the development of supporting networks, and
can result in higher healthcare costs; the total has gained particular momentum since 2016.19 This
healthcare costs of patients with polypharmacy evolution highlights the growing acknowledgment
are twice as high as those of patients without of deprescribing as a crucial strategy in optimizing
polypharmacy.12 Affordability of drug treatments is drug treatment regimens to meet the specific needs
already problematic, given that, for example, nearly and goals of individual patients. Concurrently, the
one third of older adults in the United States with substantial growth in randomized controlled trials
multiple chronic conditions spend more than 20% of evaluating deprescribing interventions attests to the
their income on medical care.13 increasing emphasis on evidence based approaches.
One way to tackle polypharmacy is via deprescribing, Several excellent reviews of deprescribing
which can be defined as the “systematic process of interventions in older adults exist, but they differ
identifying and discontinuing drugs when existing slightly in focus; for example, some are limited to
or potential harms outweigh existing or potential comprehensive medication review interventions,
benefits within the context of an individual patient’s or target a specific population such as community
the bmj | BMJ 2024;385:e074892 | doi: 10.1136/bmj‑2023-074892 1

dwelling, frail, or multimorbid.20-23 This narrative barriers at the patient, provider, and system levels.
review summarizes randomized controlled trials One example of a patient barrier is uncertainty of
that assess deprescribing interventions addressing outcomes from deprescribing (and a fear of negative
polypharmacy in older adults. consequences). Other patient barriers could be poor
access to deprescribing education, or difficulty in
Prevalence of polypharmacy understanding medical jargon.30 31 Deprescribing of
Over the past few decades, polypharmacy has a drug treatment can also represent a radical change
become a common and widespread problem among for patients with a chronic condition, who might
older adults. In the US, for example, the prevalence have been told for a long time to focus on achieving
of polypharmacy among adults aged 65 and older adequate disease control (eg, low A1c in the case of
increased from 13% in 1998 to 43% in 2014,24 25 diabetes).32
with the most recent estimates from 2017-2018 at
45%.26 This increase was driven in particular by the Provider barriers
growing use of cardioprotective and antidepressant Meanwhile, providers can also lack training and
drug treatments,24 and the highest prevalence of evidence on how to deprescribe (eg, how to taper and
polypharmacy is seen among populations with heart monitor), and can also lack knowledge and experience
disease.26 Additional reasons for increases in the use in engaging in complex conversations about
of drug treatments include the start of Medicare Part deprescribing.31 33-35 Providers themselves might fear
D (ie, prescription drug coverage for older adults) in the potential consequences of discontinuing drug
2006, as well as quadrupled spending on direct-to- treatments (eg, potential adverse drug withdrawal
consumer pharmaceutical advertising (from $985 events, inadequate disease control) especially if they
million in 1996 to $4.24 billion in 2005).27 do not have guaranteed follow-up with the patient.
Similarly, a survey conducted across 17 European Another provider barrier is inertia around making
countries and Israel also revealed a high prevalence of changes to drug treatments when patients are not
polypharmacy in adults aged 65 and older, varying from experiencing any drug treatment related problems.
26% to 40%, with the lowest estimates in Switzerland, Additional provider barriers include consultation
Croatia, and Slovenia and the highest estimates in constraints (eg, insufficient time or resources
Portugal, Israel, and the Czech Republic.28 In other to support deprescribing), uncertainty around
regions of the world, the prevalence of polypharmacy discontinuing a drug treatment that, for example,
was 46% in Hong Kong, 39% in Taiwan, 32% in South was initiated by another provider, uncertainty
Korea, and 20% in Australia.29 around roles and responsibilities among providers,
Whereas polypharmacy is a pervasive phenomenon and poor communication and collaboration among
in contemporary healthcare, particularly as providers.31 33-35 Many of these barriers are due to the
individuals contend with complex and coexisting healthcare environment in which providers work.
health conditions, a distinction must be made
between inappropriate polypharmacy and appropriate System barriers
polypharmacy, which ensures optimal patient care. Many system barriers exist. One example is
Inappropriate polypharmacy refers to the excessive, a culture of diagnosing and prescribing in
unnecessary, or unmonitored use of drug treatments, medicine.31 33 34 Evidence based guidelines often
potentially leading to adverse effects, drug–drug recommend prescribing medicine but do not make
interactions, and diminished overall wellbeing. On recommendations on when to later stop the medicine.
the contrary, appropriate polypharmacy entails the Evidence based guidelines also focus on a single
deliberate and evidence based use of multiple drug disease, and evidence based guidelines for older
treatments to serve the specific needs of a patient, adults with multimorbidity are lacking. Care itself
often stemming from the complexity of their medical for these older adults is fragmented, with multiple
conditions. In the context of deprescribing, the specialists and potential delays and/or mishaps
focus shifts to identifying instances of inappropriate in communication, which can further contribute
polypharmacy and streamlining drug treatment to inappropriate polypharmacy. Additionally, the
regimens, to align with the principles of appropriate payment incentive structure in healthcare does
polypharmacy. Thus, the objective of deprescribing not encourage complicated conversations around
is to tailor treatment regimens to individual patient deprescribing, in-depth consideration of patient care
needs, minimize potential adverse effects, and goals, and often there is a lack of shared decision
ensure that the remaining prescribed drug treatments making tools and resources.31 33 34 Also, performance
contribute meaningfully to a patient’s overall health metrics for providers and insurance plans can
and quality of life, while accounting for the principles inadvertently encourage inappropriate overuse of
of evidence based practice. drug treatments (to ensure adequate disease control)
and make it difficult for deprescribing to attain
Barriers to deprescribing individual patient goals.36
Patient barriers
Despite the need to tackle inappropriate Barriers across settings
polypharmacy, deprescribing is not commonplace. These barriers are not uniform across healthcare
Published literature has identified a myriad of settings; primary care, hospitals, long term care, and
2 doi: 10.1136/bmj‑2023-074892 | BMJ 2024;385:e074892 | the bmj

private settings face unique challenges.30 35 37 For provider teams that have clear roles and
instance, primary care confronts challenges using a responsibilities related to deprescribing decisions.
diagnostic and prescribing culture, while hospitals Examples of system facilitators include resources
contend with competing inpatient tasks, patient and tailored support tools to enable deprescribing
resistance during hospitalization, and post-discharge conversations, deprescribing guidelines, and
follow-up concerns. Long term care settings grapple evidence on optimal deprescribing practices.30 31 33 35
with resource shortages and coordination gaps, and The greater availability and acceptability of non-
private settings face obstacles related to awareness, pharmacological alternatives, which allows for
commitment, and incentives for deprescribing. substitution of the deprescribed drug treatment,
Healthcare providers, including physicians, can also allow for patients and providers to feel
pharmacists, and nurses, exhibit varied attitudes more comfortable with deprescribing. At the broader
and knowledge gaps, influencing deprescribing system level, insurance plans have medication
implementation. Specific drug treatment classes, therapy management programs and have been
such as benzodiazepines, introduce unique incentivized through quality measures to monitor
challenges, including patient beliefs, lack of and encourage discontinuation of potentially
knowledge, and emotional attachments to the drug inappropriate medications.44
treatment.38 39 Finally, increasing awareness of drug treatment
overload; for example, media campaigns and reducing
Implementation strategies industry influence can also help facilitate a culture
Overcoming these barriers is paramount for successful that normalizes deprescribing.45 Facilitators and
deprescribing, and implementation science can offer barriers to deprescribing are important to consider
valuable tools and strategies. Key implementation in deprescribing interventions, and in our review of
strategies for successful deprescribing include studies, we extracted various intervention components
structured education and training for providers and that would deal with some of these facilitators and
patients to enhance knowledge and confidence, barriers.
patient centered approaches like shared decision
making and motivational interviewing, offering Source and selection criteria
non-pharmacological alternatives to reduce drug A literature review was conducted to identify
treatment reliance, and providing resources such published randomized controlled trials of
as clinical decision support tools and deprescribing deprescribing interventions in older adults with
algorithms.40 Additionally, fostering improved polypharmacy. Searches were conducted in PubMed
communication and collaboration among healthcare and Embase on 2 April 2023 using the free text
settings and providers is crucial for maintaining search terms, “deprescribing” and “polypharmacy”,
continuity and consistency of care. Integrating and filtering on randomized controlled trials,
implementation science principles requires controlled studies, systematic reviews, and meta-
understanding healthcare system complexities, analyses. We included studies that were published
securing provider buy-in, and tailoring interventions from 1 January 2012 to the day of the search and
to specific contexts, as recent research underscores were in English. We limited our search to randomized
the value of this approach in overcoming barriers controlled trials that enrolled those at least 65
and optimizing facilitators in diverse healthcare years of age and with polypharmacy (defined as
landscapes. taking at least five drug treatments). We excluded
pilot/exploratory randomized controlled trials and
Facilitators to deprescribing ancillary publications of the randomized controlled
Studies have identified patient, provider, and system trial (eg, trial protocol only, process evaluation).
facilitators that cover a wide spectrum.30 31 33 35 We also manually searched through references
Most older adults (84-88%) are willing to of identified studies and systematic reviews of
deprescribe their drug treatment, based on provider broader scope interventions for older adults with
recommendations.41 42 In fact, 67% of older adults polypharmacy, and included studies if deprescribing
report wanting to reduce the number of drug was a part of the intervention (either explicitly by
treatments they are taking, and this desire increases the term “deprescribing” or implicitly by reporting
when they are taking more drug treatments.43 Patient reduction in drug treatments as a trial outcome).
willingness and attitudes toward deprescribing vary, Two reviewers reviewed each article and any
but it should be noted that this desire on average discrepancies were resolved through discussion. We
does exist. described intervention components and summarized
Shared decision making processes with clear key findings based on primary outcomes and any
communication and a gradual introduction of key secondary outcomes that were reported in the
the topic, as well as active patient and caregiver publication abstract. This distinction was made
involvement, can enable deprescribing. Examples because many of the trials included a very long
of provider facilitators include training to achieve list of secondary outcomes. We then categorized
in-depth drug treatment knowledge related to whether the study intervention was found to have a
deprescribing outcomes (eg, potential adverse drug statistically significant effect (p<0.05) on: (a) at least
withdrawal events) along with multidisciplinary one primary outcome; (b) if not, at least one of the

key secondary outcomes; or (c) neither primary nor Similarly, additional studies were excluded if they
key secondary outcomes. We acknowledge that if a did not specify that the recruited patients had to
randomized controlled trial tested many outcomes, be using a minimum of five drug treatments (ie, the
then there could be multiplicity concerns. For this most common definition of polypharmacy), because
narrative review, we report on these outcomes the scope of this narrative review was older adults
without adjustment and are limited by what was with polypharmacy.
reported on in the randomized controlled trial.
Secondarily, we searched for ongoing randomized Results
controlled trials of deprescribing interventions in Out of 433 articles identified, 21 articles met all
older adults with polypharmacy and applied the eligibility criteria (fig 1). Of these articles, 15 took
same inclusion/exclusion criteria as aforementioned. place in primary care (11 in primary care practices
We defined the randomized controlled trial as and four in community pharmacies), four focused
“ongoing” if the primary outcome results had not yet on hospital transitions, and two on nursing home
been published as a manuscript. To identify these settings (fig 2). Most studies took place in Europe or
ongoing studies, we documented any trials that North America, and over half (12 of 21) were cluster
had published protocols from the aforementioned randomized controlled trials (see supplementary
PubMed and Embase searches that did not yet have table 1). While the majority (12 of 21) targeted
primary outcomes results reported in a manuscript, patients aged ≥65, four studies targeted patients
and also searched through the ClinicalTrials.gov and aged ≥70, and five studies targeted patients aged
the International Standard Randomised Controlled ≥75 (figs 3-7). The majority (12 of 21) examined
Trial Number Registry databases. populations with at least five drug treatments,
When conducting this narrative review, we while eight studies used higher thresholds (eg, at
identified several completed studies46-50 and least 7, 8, 10, or 15 drug treatments). Three studies
ongoing studies51 52 that were excluded because they additionally targeted deprescribing of specific
included slightly younger populations (minimum of drug classes (eg, benzodiazepines, psychotropics,
50, 55, or 60 years of age). Similar to prior reviews, anticholinergics). In addition to targeting older
we chose an age cutoff of ≥65 because interventions populations with polypharmacy, five studies further
and outcomes can vary for different ages.20-22 For focused on frail populations or those with multiple
example, the Beers criteria that are intended for use chronic conditions, alongside specific disease states
in older adults aged ≥65 define a commonly used list such as dementia or cardiovascular disease.
of potentially inappropriate medications that might All studies compared the intervention with usual
be used if interventions are targeting older adults.53 care. We found a wide variety of interventions,
with most including more than one component
to overcome different barriers to deprescribing.
Common intervention components explicitly
434
Studies from databases/registers
described in studies included medication reviews,
295 Embase 135 PubMed 3 Citation searching 1 Medline shared decision making processes and/or a focus
on patient care priorities, active involvement of
a multidisciplinary team, training for healthcare
49
Duplicates removed
professionals, electronic clinical decision support
tools or websites, patient facing deprescribing
educational materials, and involvement of family
385
(fig 7). Below, we summarize the intervention and
Studies screened
309
Studies excluded for not meeting inclusion
criteria during title/abstract screening stage Nursing
home
2
76
Studies assessed for eligibility
Hospital
55 4
Studies excluded for not meeting inclusion
criteria during full text screening stage
5 Not randomized controlled trial
5 Not in older adults (≥65 years)
37 Not randomized controlled trial results (protocol, pilot, etc) Primary
8 Not polypharmacy (≥5 meds) care
15
21
Studies included in review
Fig 1 | Flow diagram of included studies. Fig 2 | Number of studies by targeted setting.

Trial Care setting Intervention* Total Key results† Effect of

Patient sample intervention
characteristics size
Primary care
Medication reviews (n=2)
Lenander Primary care Pharmacist reviewed n=209 Primary: significant decrease in DRPs for intervention group (from 1.73 per patient at Intervention
et al, center questionnaire completed by baseline to 1.31 at follow-up, p<0.05) but not for control group at 12 months. However, affected ≥1
201460 patient regarding drug no significant difference in change in number of DRPs between groups primary
Age: ≥65 years treatments. Pharmacist met outcome
Drug treatments: with each patient and Larger reduction in number of drugs in intervention group versus control group
≥5 provided recommendations (p<0.046) at 12 months
to patients and GPs
Secondary: no significant differences in healthcare use between groups. No change in
self-rated health in intervention group; decrease in control group (p<0.02), resulting in
a significant difference in change in self-rated health between groups (p<0.047)
Jódar- Community Pharmacists underwent a n=1403 Primary: greater reduction (0.21 ± 0.06 drugs, 95% CI 0.092 to 0.335) in number of Intervention
Sánchez pharmacies three day training course of drug treatments in intervention group versus control group at six months affected ≥1
et al, medication review and primary
201561 Age: ≥65 years follow-up, and had visits by a Intervention group quality of life (per EQ-5D-3L) improved by 0.0528 ± 0.20 (p<0.001). outcome
Drug treatments: facilitator during the six Worsening was seen for control group (but not significant)
≥5 month follow-up.
Pharmacists and patients The mean total cost was €977.57 ± 1455.88 for intervention group and €1173.44 ±
had follow-up visits every 1.2 3671.65 for control group at six months. In the cost–utility analysis, the intervention
months was the dominant strategy
Medication reviews involving multidisciplinary teams (n=2)

Köberlein- General practices Comprehensive drug n=162 Primary: mean MAI score decreased (indicating improvement in appropriateness) Intervention
Neu et al, treatment management, significantly (p≤0.001) from the control phase (29.21, 95% CI 26.09 to 32.33) to the affected ≥1
201662 Age: ≥65 years which includes the collection intervention phase (22.27, 95% CI 19.00 to 25.54) at 15 months primary
Drug treatments: of information on the drugs outcome
≥5 each patient took, the way Secondary: number of DRPs declined
Other: ≥3 chronic they were stored, the
disorders affecting patient's drug intake and
two different handling, and any problems
organ systems; ≥1 that arose with
cardiovascular pharmacotherapy.
disease Interprofessional team
including PCP, pharmacist,
and homecare specialist
Romskaug Family practitioner (a) Clinical geriatric n=174 Primary: intervention group had a higher mean HRQoL score than control group, with Intervention
et al, practices assessment of patient an estimated between group difference of 0.045 (95% CI 0.004 to 0.086, p=0.03) at 16 affected ≥1
202063 combined with medication weeks primary
Age: ≥70 years review; (b) geriatrician and outcome
Drug treatments: family practitioner meeting; Secondary: more drug withdrawals, reduced dosages, and new drug regimens started
≥7 and (c) clinical follow-up in the intervention group
Other: drug
treatments
administered by
home nursing
service
Medication reviews including patient care priorities (n=1)

McCarthy General practices General practices were given n=404 Primary: both intervention and control groups had reductions in the number of Intervention
et al, access to the SPPiRE medicines with a small but significantly greater reduction in the intervention group affected ≥1
202264 Age: ≥65 years website, where they (incidence rate ratio 0.95, 95% CI 0.899 to 0.999, p=0.045) at six months primary
Drug treatments: completed an educational outcome
≥15 module and used a template No significant effect on the odds of having ≥1 PIM between groups
for an individualized patient
medication review that
identified PIMs, opportunities
for deprescribing, and
patient priorities for care
Medication reviews with a focus on shared decision making (n=1)
Mortsiefer General practices General practices were given n=510 Primary: no significant difference between groups in number of hospitalizations within Intervention
et al, three training sessions on 12 months did NOT affect
202365 Age: ≥70 years family conferences, a primary
Drug treatments: deprescribing guideline, and Secondary: mean (SD) number of drug treatments decreased from 8.98 (3.56) to 8.11 outcomes, but
≥5 a toolkit with relevant (3.21) at six months and to 8.49 (3.63) at 12 months in the intervention group, and did affect ≥1
Other: frailty nonpharmacologic from 9.24 (3.44) to 9.32 (3.59) at 6 months and to 9.16 (3.42) at 12 months in the key secondary
syndrome, life interventions. Three GP led control group, with a significant difference at six months (p=0.001) outcome (as
expectancy of ≥6 family conferences for shared reported in
months, and no decision making, including After six months, the mean (SD) number of PIMs was significantly lower in the publication
moderate or the participants and family intervention group (1.30 (1.05)) than in the control group (1.71 (1.25) (p=0.04)). No abstract)
severe dementia caregivers and/or nursing significant difference after 12 months
services, were subsequently
held per patient at home over
nine months
Fig 3 | Summary of findings from published deprescribing randomized controlled trials in older adults with polypharmacy (part 1). *Unless noted,
the control arm was usual care. †Results on secondary outcomes were included if they were notable enough to be included in the abstract. Focus
on adjusted results and intention-to-treat analyses when available. DRP=drug related problem; EQ=EuroQol; HRQoL=health related quality of
life; MAI=Medication Appropriateness Index; PCP=primary care physician; PIM=potentially inappropriate medication; SD=standard deviation;
SPPiRE=Supporting Prescribing in Older Adults with Multimorbidity in Irish Primary Care.


Multifaceted medication reviews (involving multidisciplinary teams and focusing on patient goals or shared decision making) (n=4)
Van der Community Medication review by n=157 Primary: no significant difference between groups in percentage of patients whose DBI Intervention
Meer et al, pharmacies community pharmacist in decreased by ≥0.5 at three months did NOT affect
2018 66
collaboration with the primary
Age: ≥65 years patient’s GP and patient Secondary: intervention patients scored higher on the digit symbol substitution test, outcomes, but
Drug treatments: measure of cognitive function (OR 2.02, 95% CI 1.11 to 3.67, p=0.021), and reported did affect ≥1
≥5 fewer sedative side effects (OR 0.61, 95% CI 0.40 to 0.94, p=0.024). No significant key secondary
Other: ≥1 difference in other secondary outcomes outcome (as
psycholeptic / reported in
psychoanaleptic publication
drug treatment abstract)
and DBI of ≥1
Mahlk- General practices Medication review by three n=579 Primary: no significant difference between groups in non-elective hospital admissions Intervention
necht et experts (internal medicine or death (composite endpoint) within 24 months did NOT affect
al, 202167 Age: ≥75 years specialist, clinical primary
Drug treatments: pharmacologist, and Secondary: falls occurred less frequently in the intervention group (adjusted OR 0.55, outcomes, but
≥8 evidence based medicine 95% CI 0.31 to 0.98, p=0.04). No significant differences for other outcomes did affect ≥1
expert) who provided specific key secondary
recommendations for drug outcome (as
discontinuation reported in
publication
abstract)
Campins Primary care Pharmacist reviewed drug n=503 Primary: intervention group had a significantly lower mean number of prescriptions per Intervention
et al, 2017 centers treatments according to the patient compared with control group (10.03 versus 10.91, p=0.001) immediately after affected ≥1
GPGP algorithm and the primary
Age: ≥70 years STOPP/START criteria and Intervention group was more likely to have drug treatment discontinuation (OR=1.85, outcome
Drug treatments: provided recommendations 95% CI: 1.17 to 2.90), dose adjustment (OR=3.94, 95% CI 2.70 to 5.74), and
≥8 to the patient's physician. substitution (OR=1.54, 95% CI 1.08 to 2.19) than control group at 12 months (also
Recommendations were seen at three and six months)
discussed with patient and
final changes made and No differences in the number of emergency visits, hospitalizations, and deaths
documented during a
face-to-face visit
Verdoorn Community Clinical medication review n=629 Primary: at six months, HRQoL (per EQ-VAS) increased more (3.4 points; 95% CI 0.94 to Intervention
et al, 2019 pharmacies focused on personal goals. (a) 5.8; p=0.006) and number of health problems with moderate to severe impact on daily affected ≥1
Patient interview by life decreased more (-0.34 problems; 95% CI −0.62 to −0.044; p=0.024) in the primary
Age: ≥70 years community pharmacist; (b) intervention group versus the control group outcome
Drug treatments: potential DRPs summarized
≥7 by pharmacist and No significant difference between groups for HRQoL measured with EQ-5D-5L or total
recommendations provided; number of health problems at three and six months
(c) pharmacist and GP have a
face-to-face meeting
regarding recommendations;
(d) plan discussed with
patient; and (e) two follow-up
appointments within three
months
Deprescribing materials sent to patients (n=2)

Bayliss et Primary care (a) An educational brochure n=3012 Primary: no significant difference between groups in number of long term drug Intervention
al, 202269 clinics and a questionnaire on treatments per individual and the percentage of individuals prescribed ≥1 PIMs at six did NOT affect
attitudes toward months primary
Age: ≥65 years deprescribing were mailed to outcomes or
Drug treatments: patients before a primary key secondary
≥5 long term care visit; and (b) clinicians outcomes
Other: dementia were notified about the reported in
or mild cognitive mailing and received abstract
impairment with ≥ deprescribing tip sheets
1 chronic medical (distributed at monthly clinic
conditions meetings)
Tannenbaum Community Community pharmacy n=261 Primary: 27% of the intervention group discontinued benzodiazepine use compared Intervention
et al, pharmacies randomized to direct-to- with 5% of the control group (risk difference, 23% (95% CI 14% to 32%) at six months affected ≥1
201468 consumer educational primary
Age: ≥65 years intervention describing the Secondary: dose reduction occurred in an additional 11% (95% CI 6% to 16%) outcome
Drug treatments: risks of benzodiazepine use
≥5 and a stepwise tapering
Other: ≥1 protocol
benzodiazepine
the control arm was usual care. †Results on secondary outcomes were included if they were notable enough to be included in the abstract. Focus
on adjusted results and intention-to-treat analyses when available. CI=confidence interval; DBI=drug burden index; DRP=drug related problem;
GP=general practitioner; GPGP= Good Palliative-Geriatric Practice; HRQoL=health related quality of life; OR=odds ratio; PIM=potentially
inappropriate medication; STOPP/START=Screening Tool of Older Person’s Prescriptions/Screening Tools to Alert Doctors to Right Treatment.


Deprescribing clinical decision support tool (n=2)
Rieckert General practices An electronic decision n=3904 Primary: no significant difference between groups in unplanned hospital admission or Intervention
et al, support tool comprising a death (composite endpoint) within 24 months did NOT affect
202070 Age: ≥75 years comprehensive drug review primary
Drug treatments: to support GPs in Secondary: reduction in number of drugs was greater in the intervention group outcomes, but
≥8 deprescribing compared with the control group (adjusted mean difference −0.45, 95% CI −0.63 to − did affect ≥1
0.26, p<0.001) key secondary
outcome (as
reported in
publication
abstract)
Jungo et General practices Structured six step n=323 Primary: no significant difference between groups in drug treatment appropriateness Intervention
al, 202371 medication review based on at 12 months (as measured jointly by the change in the MAI and assessment of did NOT affect
Age: ≥65 years the use of the STRIPA, which underutilization) primary
Drug treatments: was adapted to the primary outcomes or
≥5 care setting key secondary
Other: ≥3 chronic outcomes
conditions reported in
abstract
Deprescribing clinical decision support tool with deprescribing materials sent to patients (n=1)
Fried et al, Primary care TRIM, a web tool linking an n=128 Primary: no significant difference between groups in PACIC ratings related to shared Intervention
201772 clinics at a electronic health record to a decision making, clinician and patient communication at 90 days. However, TRIM was affected ≥1
Veterans Affairs clinical decision support associated with significantly more active patient communication and facilitative primary
Medical Center system, with individualized clinician communication and with more drug treatment related communication outcome
reports to clinician and among patients and clinicians
Age: ≥65 years patient
Drug treatments: Secondary: no effect on number of drug treatments or reduction in PIMs
≥7
Hospital
Deprescribing reports sent to clinicians (n=1)
Curtin et Hospital discharge A STOPPFrail guided n=130 Primary: mean (SD) change in number of drug treatments at three months was −2.6 Intervention
al, 202073 to nursing home deprescribing plan was (2.73) in intervention group and −0.36 (2.60) in control group (mean difference 2.25 ± affected ≥1
for long term care presented to attending 0.54, 95% CI 1.18 to 3.32, p<0.001) primary
physicians who judged outcome
Age: ≥75 years whether or not to implement Secondary: mean change in monthly drug treatment cost was –$74.97 ± $148.32 in
Drug treatments: recommended drug intervention group and –$13.22 ± $110.40 in control group (mean difference $61.74 ±
≥5 treatment changes 26.60, 95% CI 8.95 to 114.53, p=0.02). No significant differences between groups for
Other: advanced other secondary outcomes
frailty
Deprescribing reports sent to clinicians and patients from deprescribing clinical decision support tool (n=1)
McDonald Hospital discharge Personalized reports of n=5698 Primary: no significant difference between groups in reduction of ADEs within the first Intervention
et al, deprescribing opportunities 30 days post-discharge did NOT affect
202274 Age: ≥65 years generated by MedSafer primary
Drug treatments: software to address usual Secondary: deprescribing increased from 29.8% of control to 55.4% of intervention outcomes, but
≥5 home drug treatments and participants (absolute risk difference 22.2%, 95% CI 16.9% to 27.4%). No difference in did affect ≥1
Other: expected measures of prognosis and ADWEs between groups key secondary
survival of >3 frailty were sent to outcome (as
months physicians, pharmacists, reported in
patients, and family publication
members abstract)
Medication reviews (n=2)

Basger et Hospital discharge Discharge drug treatment n=183 Primary: no significant difference in number of prescribing appropriateness criteria Intervention
al, 201575 to home counselling and a medication applicable and met in intervention group, compared with control group, between did NOT affect
review by a clinical follow-up and discharge. No significant difference in HRQoL (per 36-Item Short Form primary
Age: ≥65 years pharmacist. Recommenda- Health Survey), except for the vitality subdomain (p=0.04) outcomes or
Drug treatments: tions were sent to GPs of key secondary
≥5 intervention group patients Eighty-eight intervention group patient medication reviews identified 750 causes of outcomes
DRPs (8.5 ± 2.7 per patient). Of these causes, 76.4% were identified by application of reported in
the prescribing appropriateness criteria set. GPs implemented 42.4% of recommenda- abstract
tions at three months
the control arm was usual care. †Results on secondary outcomes were included if they were notable enough to be included in the abstract. Focus on
adjusted results and intention-to-treat analyses when available. ADE=adverse drug event; ADWE=adverse drug withdrawal event; CI=confidence
interval; DRP=drug related problem; GP=general practitioner; HRQoL=health related quality of life; MAI=Medication Appropriateness Index;
PACIC=Patient Assessment of Care for Chronic Conditions; SD=standard deviation; STOPPFrail=Screening Tool of Older Persons Prescriptions in
Frail adults with limited life expectancy; STRIPA=Systematic Tool to Reduce Inappropriate Prescribing Assistant; TRIM=Tool to Reduce Inappropriate
Medications.


Olsson et Hospital discharge At discharge from hospital, n=150 Primary: no significant differences between groups in quality of life (per EQ-5D and Intervention
al, 201276 to home patients were registered in EQ-VAS) or quality of prescriptions (eg, number of drug treatments, PIMs) at six and 12 did NOT affect
the care planning system and months primary
Age: ≥75 years message was sent to the outcomes or
Drug treatments: research center. Patients key secondary
≥5 were randomized to one of outcomes
three groups: reported in
• Group A (control): home abstract
visit by study nurse within
one month after discharge,
quality of life survey by mail
at six months, and second
home visit by study nurse at
12 months
• Group B (intervention): as
group A plus a letter with a
prescription review sent to
PCP
• Group C (intervention): as
group B plus drug treatment
record with drug regimen and
indications sent to the
patient to enable participa-
tion in their drug treatment,
accompanied by an
instruction to use the record
throughout the healthcare
system, make notes, and
discuss their drug treatment
with their physician
Nursing home
Medication reviews involving multidisciplinary teams (n=2)
Kua et al, Nursing homes Five step deprescribing n=295 Primary: no reduction in falls at six months Intervention
202177 intervention involving a did NOT affect
Age: ≥65 years multidisciplinary team care Secondary: intervention was associated with a reduction in mortality (HR 0.16, 95% CI primary
Drug treatments: medication review with 0.07 to 0.41, p<0.001) and number of hospitalized residents (HR 0.16, 95% CI 0.10 to outcomes, but
≥5 pharmacists, physicians, and 0.26, p<0.001) did affect ≥1
nurses key secondary
Pre-post analysis showed reduction in pill burden at the end of the study and a outcome (as
conservative daily cost saving estimate of $11.42 (S$15.65) for the study population reported in
publication
About three quarters of deprescribing interventions were accepted by physicians abstract)
Milos et al, Nursing home or Drug treatments were n=369 Primary: compared with baseline, number of intervention group patients with ≥1 PIM Intervention
201376 community reviewed by trained clinical and number of intervention group patients using ≥10 drugs decreased at two months affected ≥1
pharmacists based on nurse (p=0.007 and p=0.001, respectively). No significant changes in control group patients primary
Age: ≥75 years initiated symptom outcome
Drug treatments: assessments with team Secondary: no changes in number of patients using ≥3 psychotropics, although the
≥10 based or distance feedback dosages of these drugs tended to decrease
Other: ≥3 to the physician
psychotropics
the control arm was usual care. †Results on secondary outcomes were included if they were notable enough to be included in the abstract. Focus on
adjusted results and intention-to-treat analyses when available. HR=hazard ratio; PIM=potentially inappropriate medication; S$=Singapore dollar;
VAS=Visual Analogue Scale.
key findings from each randomized controlled trial Primary care

according to setting. We highlight whether study Historically, medication reviews with the patient
interventions were found to have a significant impact have been a common approach to optimizing drug
on at least one primary outcome assessed; or if not, treatment management among older adults with
at least one key secondary outcome; or none, and polypharmacy in the primary care setting. These
report on that impacted outcome (figs 3-7). Within medication reviews typically consist of a healthcare
setting, we also organize the studies based on the professional, such as a pharmacist, reviewing
components included in the intervention. This a patient’s list of drug treatments, identifying
categorization is helpful in framing our findings, potential drug related problems, meeting with the
but not absolute, as there could be overlap and patient, and providing recommendations to the
variation in how much focus was given to each of the patient, physician, or both. Medication reviews can
components. be broad in nature and include patient education

16 care provider would send records to a homecare

Study interventions could include multiple components specialist, who would collect information to help
inform a pharmacist’s medication review. This
12
medication review was then followed up with
No of studies
recommendations that were sent back to the

8 homecare specialist and primary care provider.62 This
intervention was found to decrease the mean drug
4 treatment appropriateness index score (indicating
improvement in appropriateness) from the control
phase to the intervention phase at 15 months
0 (p≤0.001; primary outcome). In another medication
er ng
fo eam of
ie r
at de bsit on
m t
ie n
Pa ort clin sion are review intervention, the multidisciplinary team

tid in iorit g o
fa en
tie cis rev tio
ily
w
nt ool al d l
In ilas
e
yt t
at ribi
i
a
we cis
es hc
ar en
of vem
pr in
ica
included a geriatrician and a family practitioner who

su tron rof alt
l m sc
Ac are mak
or e
Tr iplin lvem
ed
l
na re
p he
vo
M
io p
met after a medication review and clinical geriatric
c n
t ic
isc vo
r
nt io
uc ing
g
assessment. This intervention led to a higher mean

ul ve
in
pp ic
pa e
ed c
ain
n dd
m ti
health related quality of life (HRQoL) score in the

f
s o are
ec
tie
cu h
intervention group versus the control group (p=0.03;

El
fo S
Intervention components primary outcome).63

Yet another component added to medication
Fig 7 | Frequency of intervention components.
reviews was an electronic decision support
website and a focus on patient care priorities
or shared decision making, which can align
deprescribing decisions with patient goals, facilitate
and/or drug treatment changes such as reductions communication between patients and providers,
in dose, discontinuing a drug treatment, or adding and reduce uncertainty in the deprescribing process.
drug treatments when appropriate. In our review, In one study, general practices were given access
two thirds (10 of 15) of primary care interventions to a website that provided an educational module
centered around medication reviews, and all and template for general practitioners to conduct
affected at least one primary or secondary outcome medication reviews that identified potentially
(with a majority (7 of 10) affecting the primary inappropriate medications, opportunities for
outcome; figs 3-7). deprescribing, and patient priorities for care.64 This
Medication reviews can vary depending on study found a larger reduction in the number of drug
how the drug treatment data are collected, who treatments in the intervention group versus control
is performing the review, and the extent to which group at six months (p=0.045; primary outcome).
follow-up is performed, along with whether In a second study, general practices were given a
additional components (such as training for the deprescribing guideline and training sessions on
healthcare professional) are provided. In one study, a family conferences, during which a medication
medication review conducted by a pharmacist based review took place with a frail patient and their
on a questionnaire completed by patients led to a family caregivers.65 While no effect was found on the
larger reduction in the number of drug treatments primary outcome (number of hospitalizations in 12
in the intervention group versus the control group months), the number of drug treatments (p=0.001)
at 12 months (p<0.046; primary outcome).60 In and number of potentially inappropriate medications
another study, pharmacist conducted medication (p=0.04; secondary outcomes) were lower in the
reviews were preceded by a three day training intervention group than in the control group at six
course for pharmacists and succeeded by six month months.
follow-up with the patient.61 Recommendations were Four more medication review interventions
made to patients, their physicians, or both, and this involved both multidisciplinary teams and focused
intervention led to a greater reduction (0.21 ± 0.06 on patient goals or shared decision making. In one
drugs, 95% confidence interval 0.092 to 0.335) in of these studies, community pharmacists conducted
the number of drug treatments in the intervention medication reviews with patients with a drug burden
group compared with the control group, improved index of ≥1 and subsequently met to discuss with
quality of life in the intervention group (p<0.001), the patient’s general practitioner, with patient
and a dominant strategy in a cost–utility analysis (all expectations and desires as key elements in final
primary outcomes). decisions.66 This study did not find an impact in the
In addition to healthcare professional training, proportion of patients who reduced their drug burden
another component commonly added to medication index by ≥0.5 at three months (primary outcome),
review interventions was the active involvement but did find an impact on cognitive function
of a multidisciplinary team, which can improve (p=0.021) and fewer sedative side effects (p=0.024;
communication and minimize provider barriers secondary outcomes). Another study included
around uncertainty in role regarding changes a medication review by three experts (internal
to the patient’s drug treatment regimen. In one medicine specialist, clinical pharmacologist, and
such medication review intervention, a primary evidence based medicine expert) who provided

Table 1 | Characteristics of ongoing deprescribing randomized controlled trials in older adults with polypharmacy
Trial name/acronym* Care setting Patient Estimated Estimated study
Registry number characteristics Intervention† Outcome measures sample size completion
SPIDER54 55 Primary care practices Participating practices will form Primary: PIM reduction at 12 months n=2576 March 2025
NCT03689049 Age: ≥65 years interprofessional learning collaboratives
Drug treatments: ≥10 and work with quality improvement Secondary:
coaches to review electronic medical patient and care provider perceptions of the
record data provided by their regional intervention, cost-utility of the intervention
practice based research networks, identify
areas of improvement, and develop and
implement changes.
PARTNER56 General practices and Intervention: (a) educational material for GPs Primary: reduction in PSA-PIM exposure, n=352 December 2024
NCT05842928 community pharmacies and pharmacists on PSA-PIM deprescribing; reflected by a reduction of ≥0.15 points on the
Age: ≥65 years (b) a moderated interprofessional workshop; PSA-PIM DBI at six months
Drug treatments: ≥5 (c) patient empowerment via a pre-planned
Other: ≥1 psycholeptic, patient–pharmacist consultation facilitated Secondary:
sedative, or by empowerment leaflets; and (d) shared frequency of deprescribing, total exposure
anticholinergic drug decision making as part of a pre-planned with PSA-PIM, frequency of new PSA-PIMs,
PIM patient-GP consultation. frequency of other PIMs, ADEs,
Control: usual care plus a pre-planned number of falls and hospitalizations due to
patient-pharmacist consultation to update falls, cognition, quality of life, insomnia
drug treatment plans and conduct a drug
treatment safety check with no particular
focus on PSA-PIM.
TAPER57 Family doctor practice Comprehensive multidisciplinary medication Primary: number of drug treatments at six n=360 June 2023‡
NCT02942927 Age: ≥70 years review by pharmacists and physicians months
Drug treatments: ≥5 in conjunction with patients, focused on
reducing drug treatment burden. Secondary:
quality of life, cognition, fatigue, pain, patient
enablement, sleep, disease burden, nutritional
status, treatment burden, falls, physical functional
capacity and ability, use of healthcare resources,
successful discontinuation or dose reduction,

changes in drug treatment side effects and
symptoms, serious adverse events, and drug
treatment self-efficacy
Pharmacist/family physician best/worst aspects

of intervention, confidence in drug treatment
discontinuation, experience with deprescribing
process, patient experience with deprescribing
process, satisfaction with intervention and care
around drug treatments, cost effectiveness
The general practice General practices Drug treatment optimization delivered Primary: number of PIMs at four months n=120 June 2023‡
based pharmacist Age: ≥65 years by targeted patient medication reviews.
medicines optimization Drug treatments: 5 Pharmacist will meet with both patients and Secondary:
program: a pilot prescribers. number of repeat drug treatments, percentage
cluster RCT, process of patients with polypharmacy, drug treatment
and economic changes (including deprescribing), ADEs, ADWEs,
evaluation58 59
ISRCTN18752158 quality of life, patient attitudes towards
deprescribing, treatment burden, patient
beliefs about necessity of drug treatments
*If available.
†Unless noted, the control arm will be usual care.
‡Although website reports that the study has been completed, the publication of a peer-reviewed journal article reporting results had not been identified at time of search.
ADE=adverse drug reaction; ADWE=adverse drug withdrawal event; DBI=drug burden index; GP=general practitioner; MAI=Medication Appropriateness Index; PIM=potentially inappropriate
medication; PSA=psycholeptic, sedative, or anticholinergic drug; RCT=randomized controlled trial.
specific recommendations for drug discontinuation fewer drug treatments (p=0.001) immediately after
to a general practitioner, who was invited to act on the review, and a greater likelihood of drug treatment
the recommendations based on a shared decision discontinuation, dose adjustment, and substitution
making process with the patient.67 This intervention at three, six, and 12 months (primary outcomes).
was not found to affect hospital admissions or death In a fourth study, the medication review conducted
(primary outcome) but did lead to fewer falls (p=0.04; by the pharmacist incorporated goal setting by
secondary outcome). In a third study, a pharmacist the patient and was followed up with face-to-face
performed a medication review with the final meetings with the patient’s general practitioner and
decisions agreed upon by both the physician and the discussion and follow-up with the patient. Compared
patient in a face-to-face visit. This intervention led to with the control group, this intervention led to an

improvement in HRQoL (3.4 points, 95% confidence can help providers with specific, actionable steps
interval 0.94 to 5.8, p=0.006) and a reduction in the in deprescribing, such as which drug treatment to
number of health problems with moderate to severe deprescribe, level of priority (among multiple drug
impact on daily life in the intervention group (−0.34 treatments that should be deprescribed), and how
problems, 95% confidence interval −0.62 to −0.044, to taper and monitor. In one study, a deprescribing
p=0.024) at six months (primary outcomes). plan was generated by a study physician,73 and in
Beyond medication reviews with patients, the second study, a report providing deprescribing
other interventions focused on patient facing opportunities was generated by clinical decision
deprescribing educational materials,2 deprescribing support software.74 In the first study, the report was
clinical decision support tools,3 or both.1 Patient sent to the patient’s physician, and in the second
facing deprescribing educational materials can study, the report was sent to physicians, pharmacists,
empower patients to take a more active role patients, and family members. Although the second
in deprescribing decisions, thereby serving as study was not shown to reduce adverse drug events
facilitators to deprescribing. Of the two interventions (primary outcome), both interventions led to
focused on patient facing deprescribing educational deprescribing, as evidenced by a greater reduction
materials, one was focused on benzodiazepines in the mean number of drug treatments after three
and provided specific information around the risks months (−2.6 intervention group v −0.36 control
of benzodiazepine use and a stepwise tapering group, mean difference 2.25, 95% confidence
protocol.68 This study was conducted by community interval 1.18 to 3.32; primary outcome for the first
pharmacies and reduced benzodiazepine use (27% of study) or increased deprescribing within 30 days
the intervention group discontinued benzodiazepine (29.8% control group v 55.4% intervention group,
use v 5% of the control group, risk difference adjusted risk difference 22.2%, 95% confidence
23%, 95% confidence interval 14% to 32%) at six interval 16.9% to 27.4%; secondary outcome for the
months (primary outcome). The other study mailed second study).
a general deprescribing educational brochure and Two additional studies involved either a
questionnaire to patients with dementia or mild pharmacist75 or a physician76 conducting a medication
cognitive impairment and their family members review, and then sending recommendations to the
prior to a primary care visit.69 This was coupled with patient’s general practitioner. In the second study,
clinician notification and deprescribing tip sheets, two intervention arms were tested to allow for further
but the intervention was not found to impact the patient engagement in one of those arms (eg, a
primary outcomes (ie, number of long term drug drug treatment record sent to the patient).76 Across
treatments or proportion of individuals prescribed ≥1 both studies, the interventions were not found to
potentially inappropriate medication) at six months. affect prescribing appropriateness, prescribing
Deprescribing clinical decision support tools quality (eg, number of drug treatments, number of
coupled with shared decision making processes can potentially inappropriate medications), or HRQoL
help overcome patient, provider, and system barriers (all primary outcomes). One study did report on
to deprescribing. Two such studies applied clinical implementation outcomes; for example, that 750
decision support tools that reviewed drug treatments, causes of drug related problems were identified, and
and identified potential problems for providers to that general practitioners implemented 42.4% of
then make subsequent treatment changes based on recommendations.75
shared decision making with the patient.70 71 Neither
study was found to impact their primary outcome Nursing homes
(ie, hospital admission or death within 24 months, The two interventions targeting nursing home
drug treatment appropriateness at 12 months); populations were both medication reviews involving
however, one study did find a greater reduction in multidisciplinary teams including pharmacists,
number of drug treatments (p<0.001), which was physicians, and nurses. The first intervention also
a secondary outcome.70 A fifth study combined use optionally involved family members for patients with
of a clinical decision support tool in primary care cognitive impairment, and was not found to reduce
clinics with individualized patient facing materials falls at six months (primary outcome), but was found
that included brief coaching on how to discuss to reduce mortality (p<0.001) and hospitalization
concerns with the provider.72 The intervention (p<0.001; secondary outcomes).77 The second study
was found to be associated with significantly more focused on older populations (aged ≥75 years) taking
active patient communication, facilitative clinician ≥10 drug treatments (specifically, ≥3 psychotropics),
communication, and drug treatment related and was found to reduce the number of patients with
communication among patients and clinicians ≥1 potentially inappropriate medication and the
(primary outcomes). number of patients using ≥10 drugs at two months
(p=0.007 and p=0.001, respectively; primary
Hospitals outcomes).78
At hospital discharge, four study interventions In summary, various deprescribing interventions
focused on sending deprescribing reports to in older adults with polypharmacy have been tested
clinicians2 and medication reviews.2 Interventions in randomized controlled trials across different
generating individualized deprescribing reports settings, with most (15 of 21 studies) conducted in

primary care settings. The majority of interventions communication (fig 8), and even greater diversity
centered around medication reviews, with a mix of was observed in the secondary outcomes collected
including additional components, such as a focus on (see supplementary table 1). Of the 21 studies, just
shared decision making and/or patient care priorities, over half11 reported a significant effect on at least
multidisciplinary teams, training for healthcare one primary outcome. Another six showed an effect
professionals, electronic clinical decision support on at least one of the key secondary outcomes,
tools or websites, patient facing deprescribing and four did not show an effect on primary or key
educational materials, and involvement of family. secondary outcomes. The variability in results can be
Such diverse intervention components represent attributed to not only heterogeneity in intervention,
how complicated deprescribing is and what is but also the choice of primary outcomes. Notably,
needed to overcome the myriad of existing patient, several studies emphasized the inadequacy of using
provider, and system barriers to deprescribing. clinical outcomes like hospitalization and death as
Medication reviews with patients were generally a sole measure for deprescribing success, owing to
successful in primary care settings (7 of 10 studies challenges in translating the impact of discontinuing
showing an impact on at least one primary outcome, drugs into such downstream outcomes. Several
and all showing an effect on at least one primary or studies using HRQoL as their primary outcome,
key secondary outcome), but not always successful and one study focusing on shared decision making
in other settings such as the hospital (two of two and patient-provider communication as its primary
studies not showing an effect on primary or key outcomes, further underscored the need for a more
secondary outcomes), although the number of comprehensive understanding of appropriate key
studies was very small. Great variation in the mix clinical endpoints in deprescribing interventions.
of intervention components, as well as diversity in Furthermore, variability in drug treatment related
study population, led to small sample sizes within outcomes across deprescribing studies adds to
each stratum, making it difficult to determine if one the complexity. Among primary outcomes, drug
particular component was considered to be more treatment related outcomes included number
or less successful. Ongoing randomized controlled of drug treatments; number or proportion of
trials of deprescribing interventions in older adults potentially inappropriate medications; medication
with polypharmacy will provide more evidence, and appropriateness index, drug burden index or
further patterns should emerge as the number of other prescribing appropriateness criteria; drug
studies grows. related problems or adverse drug events; drug
Primary outcomes assessed across studies included treatment changes (such as discontinuation, dose
drug treatment related outcomes (13 studies), HRQoL adjustment, or substitution; and proportion with
or health problems with impact on daily life, clinical ≥10 drug treatments (fig 9). This diversity hinders
outcomes such as falls, emergency room visits, the comparison and generalization of findings,
hospitalizations, and deaths, cost, and outcomes emphasizing the need for standardized measures. To
related to shared decision making or patient/clinician tackle these problems, the use of core outcome sets
can provide a standardized approach to outcome
measurement and enhance comparability across
diverse populations and settings in deprescribing
All primary outcomes assessed
research.79-81 Commonly recommended outcomes
Primary outcomes for which intervention had an effect
16 within core outcome sets include drug treatment
If study had multiple primary outcomes, all were reported appropriateness, drug related problems, and
hospitalizations associated with drug treatments,
12
ensuring a more consistent and comprehensive
No of studies
evaluation of deprescribing interventions.

8 In addition to outcome variability, difficulties
such as overestimating intervention effects, limited
provider acceptance, intervention spillover effects,
4
and challenges in tracking pharmacy adherence in
real world settings contribute to study variability.
0 Recognizing the necessity of longer observation
periods aligns with the complex nature of
om nt
lif m
tio or
fa ,
ilit r
it, ath
ut t o
ily le
tc e
ll)
e
n
e)
ica ng
ou atm
st os
vis de
da rob
deprescribing interventions over time. Best practices

un ki
co C
m g,
m a
on p
ed tre
m m
oo (e
ct lth
for successful deprescribing interventions require

co sion
lat g
yr e
pa ea
re Dru
targeting provider behavior change, employing

im r h
nc co
an ci
ici de
th (o
ge ut
methods to limit contamination effects in trials (eg,

er l o
wi ife
lin d
/c re
em ica
l
of
nt ha
cluster randomized trials), powering studies for

n, in
ty
tie o s
io Cl
ali
pa ed t
clinically meaningful effect sizes, and emphasizing

Qu
lat
longer follow-up periods. These practices contribute

at
Re
liz
ita
to a more robust understanding of deprescribing

sp
Primary outcome
ho
interventions and guide the development of effective

Fig 8 | Frequency of primary outcome assessed and if an effect was shown. strategies. While study follow-up periods varied

8 training for healthcare professionals. In the SPIDER

If study had multiple medication related cluster randomized controlled trial, targeting those
primary outcomes, all were reported
taking ≥10 drug treatments in Canada, primary care
6
practices will develop interprofessional learning
No of studies
collaboratives and work with quality improvement

4 coaches.54 55 The intervention will be compared
with usual care, and the primary outcome will be
2 reduction of potentially inappropriate medications
at 12 months. Secondary outcomes include cost
effectiveness, as well as patient and care provider
0 perceptions of the intervention.
ev l em
tio te
ne g
io ,
ns f
ug y
Next, the PARTNER cluster randomized controlled
ut ion
tio r o
dr ac
te bin
ica ria
t
ss
n
n)
s)
en
ica be
10 rm
tit at
ug ob
ria cri
ed op
trial in Germany targeting patients using ≥1
bs nu
ed m
(≥ ha
dr pr
op es
m pr
m Nu
su ti
yp
d
pr pr
ap
t, on
psycholeptic, sedative, or anticholinergic drug
er ate
ol
in
ap , or
en sc
rp
l
e
ad re
lly
m di
treatments comprises a multilevel, multicomponent
BI
pe
tia
st (
or rug
,D
ju ge
Hy
v
en
intervention.56 Firstly, educational material will be

AI
ad han
t
M
Po
se c
provided for general practitioners and pharmacists

do tion
on deprescribing psycholeptics, sedatives, and

ica
ed
anticholinergics, and a moderated interprofessional

M
Medication related primary outcome workshop will take place. Secondly, leaflets will be
Fig 9 | Frequency of specific drug treatment related primary outcomes. used to encourage patient empowerment during a
patient-pharmacist consultation. Thirdly, a patient-
general practitioner consultation involving shared
decision making will take place. This intervention
will be compared with usual care, plus a patient-
(fig 10), with six months being the most commonly
pharmacist consultation updating plans for drug
used timeframe, and 22 of 25 primary outcome
treatment (but without a focus on psycholeptics,
measures within 12 months, the question of whether
sedatives, or anticholinergics). The primary
deprescribing interventions have long term effects
trial outcome will be reduction in exposure to
remains unanswered. Two studies with 24 months of
psycholeptics, sedatives, or anticholinergics as
follow-up conducted in general practices indicated
measured by a point reduction of ≥0.15 in drug
effectiveness in reducing falls and the number of
burden index at six months. Secondary outcomes
drug treatments taken, suggesting potential long
include drug treatment related outcomes, such as
term benefits. However, further evidence is needed
frequency of deprescribing and frequency of other
to establish the sustained efficacy of deprescribing
potentially inappropriate medications as well as
interventions over extended periods.
quality of life and clinical outcomes such as falls, fall
related hospitalizations, cognition, and insomnia.
Emerging interventions
Two additional trials are testing interventions
Four ongoing randomized controlled trials are testing
focused on medication reviews. In the TAPER
deprescribing interventions in older adults with
randomized controlled trial targeting those ≥70
polypharmacy in Canada, Germany, and Ireland,
years in Canada, a multidisciplinary comprehensive
and are all focused on older adults who are being
medication review focused on reducing drug
seen in primary care practices (table 1). The first
treatment burden and conducted by pharmacists
two randomized controlled trials are investigating
and physicians with patients will be compared
with usual care.57 The primary outcome will be the
number of drug treatments at six months and there
are numerous secondary outcomes related to drug
If study had multiple follow-up periods for
multiple primary outcomes, all were reported
treatment use (eg, successful discontinuation or dose
8 reduction, changes in drug treatment side effects
and symptoms), quality of life, clinical outcomes
like cognition, physical functional ability, and falls,
6
healthcare resource use and cost effectiveness, and
No of studies
patient-reported deprescribing measures, such as

4 confidence in drug treatment discontinuation and
experience with the deprescribing process.
Lastly, a cluster randomized controlled trial in
2
Ireland will use targeted medication reviews, in
which pharmacists will meet with both patients and
0 prescribers.58 59 The intervention will be compared
1 2 3 4 6 12 15 24
with usual care, and the primary outcome will be
Follow-up period for primary outcome (months)
the number of potentially inappropriate medications
Fig 10 | Frequency of follow-up period for primary outcome. at four months. Secondary outcomes include drug

treatment related outcomes (eg, polypharmacy, Wales have produced guidance documents around
drug treatment changes, adverse drug reactions, management of polypharmacy in older adults,
adverse drug withdrawal events), quality of life, and including recommendations on how to deprescribe
patient reported deprescribing measures (eg, patient specific drug classes.90 Not all drug classes have
attitudes toward deprescribing and the necessity of deprescribing guidelines, and evidence is still
drug treatments). needed to support recommendations around optimal
In summary, four ongoing randomized controlled tapering and monitoring strategies. While a previous
trials are being conducted in primary care practices, review identified several drug classes at increased
with a mix of intervention components such as risk of adverse drug withdrawal events,91 further
medication reviews, patient empowerment leaflets, evidence (such as through deprescribing trials) is
and training for healthcare professionals. The needed to better understand the risk and severity of
primary outcomes are all drug treatment related, such adverse drug withdrawal events after deprescribing,
as reduction in potentially inappropriate medication how this varies, and how to minimize these potential
or based on a score measuring drug treatment risks.92 To help fill these evidence gaps, multiple
appropriateness (eg, medication appropriateness deprescribing networks are growing in Canada,93
index or drug burden index), and are measured Australia,94 the US,95 and Europe.96
over 4-12 months of follow-up. Secondary outcomes Additionally, disease specific guidelines are also
are numerous, and include newer patient reported beginning to include consideration of discontinuation
deprescribing measures (eg, attitude toward or de-intensification of treatment, especially
deprescribing and confidence in drug treatment among older adults with multiple comorbidities
discontinuation), as well as implementation and polypharmacy. For example, the American
outcomes (eg, costs, and patient/provider perception Diabetes Association guidelines and the American
of, experience with, and satisfaction with the Geriatrics Society guidelines both recommend de-
deprescribing intervention). intensification of diabetes drug treatments and
individualized glycemic targets among older adults
Guidelines with multiple comorbidities.97 98
Deprescribing guidelines, algorithms, and Polypharmacy in older adults is associated with
additional resources have been developed in recent an increased risk of using potentially inappropriate
years for specific drug classes such as proton medications,9 10 and several guidelines relate
pump inhibitors,82 diabetes drug treatments,83 to potentially inappropriate medications. These
antipsychotics,84 benzodiazepines and Z guidelines include the Beers criteria in the US,99
drugs,85 and dementia drug treatments86 by the the STOPP/START (screening tool of older persons’
deprescribing.org research team.87 Another research prescriptions/screening tools to alert doctors to right
team has also developed deprescribing guides for treatment) criteria in Europe100 and Japan,101 the
antidepressants, anticholinergics for Parkinsonism, PRISCUS list in Germany,102 the European Union (7)
antimuscarinics, sedating antihistamines, and potentially inappropriate medications (EU(7)-PIM)
opioids.88 Medstopper is a freely available web list which was developed by experts from seven
based tool that provides recommendations related to European countries,103 STOPPFrail (screening tool of
tapering and more.89 Additionally, countries such as older persons’ prescriptions in frail adults with limited
life expectancy) criteria in frail populations with
limited life expectancy,104 RASP,105 and NORGEP.106
16 Other approaches and tools developed to help
clinicians determine drug treatment appropriateness
include the drug burden index,107 the anticholinergic
12 risk scale,108 the medication appropriateness
No of studies
index,109 and the medication regimen complexity

8 index.110 Across study interventions identified in
this review, the most commonly used guidelines to
identify potentially inappropriate medications were
4
the STOPP, STOPP/START or STOPPFrail criteria (7 of
21) and Beers criteria (6 of 21; fig 11). Other ways to
0 identify potentially inappropriate medications were
STOPP, Beers Other* Not
based on country specific guidance, drug interaction
STOPP/START, stated
STOPPFrail databases (eg, LexiComp, UpToDate), EU(7)-PIM,
Guideline used in intervention to identify NORGEP, or targeting specific drug classes such as
potentially inappropriate medications† benzodiazepines or opioids.
Furthermore, quality measures have also been
Fig 11 | Frequency of guideline used to identify potentially inappropriate medications.
STOPP=screening tool of older persons’ prescriptions; START=screening tool to alert
used over the years to discourage potentially
doctors to right treatment study. *Included country specific guidelines, the EU(7)-PIM inappropriate medication use. For example, in the
list, NORGEP, drug-drug interaction databases (eg, LexiComp, UpToDate), and targeting US, the Centers for Medicare and Medicaid Services
specific drug classes like benzodiazepines and opioids. †Study interventions could has evaluated potentially inappropriate medication
apply more than one guideline. use in older populations through various quality

measures for Part D prescription drug insurance

QUESTIONS FOR FUTURE RESEARCH
plans, either generally (eg, high risk drug treatments
• How effective are deprescribing interventions in
in older people largely based on Beers criteria), or
focused on specific drug classes and disease states the long term (>2 years)? What patient, provider,
(eg, antipsychotic use among older adults with and system factors are associated with reinitiating
dementia, multiple anticholinergic drug treatments, treatments following deprescribing, and how
or multiple central nervous system active drug should these be dealt with? How sustainable are
treatments in older adults with polypharmacy).44 deprescribing interventions in real world clinical
Prescription drug plans are incentivized to reach out settings, and what are the associated costs (eg, to
to beneficiaries and reduce potentially inappropriate support staff)?
medication use to perform well on these measures, • What is the ideal primary outcome and core outcome
because these measures can potentially influence set? How might these outcomes be based on setting,
beneficiary enrollment and bonus payments. deprescribing intervention component, and study
In 2022, a new quality measure focused on population?
deprescribing benzodiazepines in older adults was • To what degree have patients been involved
developed,111 indicating that future deprescribing as stakeholders in the design of deprescribing
quality measures could be used alongside guidelines interventions, and to what extent do they affect
to incentivize deprescribing at a large scale. Similarly, effectiveness and implementation? How might patient
the Centers for Medicare and Medicaid Services input affect measures around adverse drug events?
also applies quality measures for nursing homes to • How does deprescribing differ across populations;
monitor antipsychotic and sedative use.112 for example, in under-resourced populations? How
In summary, recently developed deprescribing do social determinants of health and the influence
guidelines and algorithms have focused on collating of cultural traditions and provider bias limit the
evidence and providing recommendations (eg, effectiveness and implementation of current
whether and how to taper) for specific drug classes. deprescribing interventions?
A variety of potentially inappropriate medication • How do system level barriers such as uncoordinated
guidelines to help identify inappropriate drug health services delivery affect deprescribing?
treatment use exists, and quality measures can be How do disparate healthcare access, mistrust in
used to incentivize reduction of inappropriate drug health systems, poor communication, and provider
treatment use. As disease specific guidelines begin negligence in considering patients’/caregivers’
to include deintensification of treatment and the values, healthcare beliefs, and literacy levels affect
number of studies testing various deprescribing patients’/caregivers’ deprescribing decisions?
interventions grows, future guidelines should report • What types of culturally tailored interventions, shared
on the intervention components and implementation decision making, and educational tools specific to
strategies that have led to successful deprescribing deprescribing are most effective?
interventions, and how these vary across setting.
Conclusions
This review summarizes published and ongoing HOW PATIENTS WERE INVOLVED IN THE CREATION
deprescribing randomized controlled trials in OF THIS ARTICLE
older adults with polypharmacy, and describes We thank the US Deprescribing Research Network
important barriers and facilitators to deprescribing, Stakeholder Engagement Core and the two patient
as well as guidelines and resources that can stakeholders who provided valuable feedback,
support deprescribing. Medication reviews in including specific future directions for the ‘‘Questions
primary care settings continue to represent a for future research’’ section.
majority of deprescribing interventions, with many
interventions incorporating a mix of components.
Other intervention components included a focus
on shared decision making and/or patient care death), HRQoL, and more. Ongoing trials are
priorities, active involvement of multidisciplinary focused on primary care settings and are adding
teams, training for healthcare professionals, patient newer patient reported deprescribing outcome
facing educational materials, and involvement of measures (eg, attitude toward deprescribing and
family members, which shows how complicated confidence in drug treatment discontinuation), as
deprescribing can be. Just over half of interventions well as implementation outcomes (eg, costs, and
were found to be efficacious based on assessment patient/provider perception of, experience with, and
of primary outcome alone, suggesting that applying satisfaction with the deprescribing intervention).
such intervention components can help to overcome AH acknowledges the US Deprescribing Research Network Junior
barriers in deprescribing. Most outcomes were Investigator Intensive Program and the AGING Initiative Multiple
Chronic Conditions Scholars Program.
assessed within 12 months of follow-up, and varied
widely: drug treatment related (eg, number of drug Funding: AH is supported by VA HSR&D (Career Development Award
IK2 HX003359) and by the US Deprescribing Research Network
treatments or number of potentially inappropriate (R24AG064025). JMP is supported by a Career Development Award
medications), clinical outcomes (eg, hospital, K23AG058788 from the National Institute on Aging.

Sponsor’s role: The funders had no role in the design, analysis, or 20 Omuya H, Nickel C, Wilson P, Chewning B. A systematic review of
preparation of the paper. The contents do not represent the views of randomised-controlled trials on deprescribing outcomes in older
the US Department of Veterans Affairs or the US Government. adults with polypharmacy. Int J Pharm Pract 2023;31:349-68.
doi:10.1093/ijpp/riad025
Competing interests: We have read and understood the BMJ policy 21 Bloomfield HE, Greer N, Linsky AM, et al. Deprescribing for
on declaration of interests and declare the following interests: community-dwelling older adults: a systematic review and meta-
AH reports funding from the US Deprescribing Research Network analysis. J Gen Intern Med 2020;35:3323-32. doi:10.1007/s11606-
(R24AG064025), honorariums and conference support from Academy 020-06089-2
of Managed Care Pharmacy, and honorariums from the Journal of 22 Ibrahim K, Cox NJ, Stevenson JM, Lim S, Fraser SDS, Roberts HC. A
Managed Care and Specialty Pharmacy. No other authors declare systematic review of the evidence for deprescribing interventions
interests. among older people living with frailty. BMC Geriatr 2021;21:258.
Contributing author statement: All authors made substantial doi:10.1186/s12877-021-02208-8
contributions to the conception of the work, drafting/reviewing for 23 Reeve J, Maden M, Hill R, et al. Deprescribing medicines in older
important intellectual content, final approval of the version to be people living with multimorbidity and polypharmacy: the TAILOR
evidence synthesis. Health Technol Assess 2022;26:1-148.
published, and agree to be accountable for all aspects of the work. The
doi:10.3310/AAFO2475
corresponding author attests that all listed authors meet authorship
24 Charlesworth CJ, Smit E, Lee DSH, Alramadhan F, Odden MC.
criteria and that no others meeting the criteria have been omitted. Polypharmacy among adults aged 65 years and older in the United
Provenance and peer review: commissioned; externally peer States: 1988-2010. J Gerontol A Biol Sci Med Sci 2015;70:989-95.
reviewed. doi:10.1093/gerona/glv013
25 National Center for Health Statistics. Health, United States, 2016:
1 Delara M, Murray L, Jafari B, et al. Prevalence and factors associated with chartbook on long-term trends in health. Hyattsville, MD. 2017.
with polypharmacy: a systematic review and Meta-analysis. BMC 26 Wang X, Liu K, Shirai K, et al. Prevalence and trends of polypharmacy
Geriatr 2022;22:601. doi:10.1186/s12877-022-03279-x in U.S. adults, 1999-2018. Glob Health Res Policy 2023;8:25.
2 Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What doi:10.1186/s41256-023-00311-4
is polypharmacy? A systematic review of definitions. BMC 27 Donohue JM, Cevasco M, Rosenthal MB. A decade of direct-
Geriatr 2017;17:230. doi:10.1186/s12877-017-0621-2 to-consumer advertising of prescription drugs. N Engl J
3 Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy Med 2007;357:673-81. doi:10.1056/NEJMsa070502
in elderly. Expert Opin Drug Saf 2014;13:57-65. doi:10.1517/1474 28 Midão L, Giardini A, Menditto E, Kardas P, Costa E. Polypharmacy
0338.2013.827660 prevalence among older adults based on the survey of health, ageing
4 Field TS, Gurwitz JH, Harrold LR, et al. Risk factors for adverse drug and retirement in Europe. Arch Gerontol Geriatr 2018;78:213-20.
events among older adults in the ambulatory setting. J Am Geriatr doi:10.1016/j.archger.2018.06.018
Soc 2004;52:1349-54. doi:10.1111/j.1532-5415.2004.52367.x 29 Lee H, Baek YH, Kim JH, et al. Trends of polypharmacy among older
5 Rawle MJ, Cooper R, Kuh D, Richards M. Associations between people in Asia, Australia and the United Kingdom: a multinational
polypharmacy and cognitive and physical capability: a British birth population-based study. Age Ageing 2023;52:afad014.
cohort study. J Am Geriatr Soc 2018;66:916-23. doi:10.1111/ doi:10.1093/ageing/afad014
jgs.15317 30 Peat G, Fylan B, Marques I, et al. Barriers and facilitators of successful
6 Gnjidic D, Hilmer SN, Blyth FM, et al. Polypharmacy cutoff and deprescribing as described by older patients living with frailty, their
outcomes: five or more medicines were used to identify community- informal carers and clinicians: a qualitative interview study. BMJ
dwelling older men at risk of different adverse outcomes. J Clin Open 2022;12:e054279. doi:10.1136/bmjopen-2021-054279
Epidemiol 2012;65:989-95. doi:10.1016/j.jclinepi.2012.02.018 31 Doherty AJ, Boland P, Reed J, et al. Barriers and facilitators to
7 Chang TI, Park H, Kim DW, et al. Polypharmacy, hospitalization, and deprescribing in primary care: a systematic review. BJGP Open
mortality risk: a nationwide cohort study. Sci Rep 2020;10:18964. 2020;4:bjgpopen20X101096.
doi:10.1038/s41598-020-75888-8 32 Pilla SJ, Meza KA, Schoenborn NL, Boyd CM, Maruthur NM, Chander G.
8 Roitto HM, Aalto UL, Öhman H, et al. Association of medication A qualitative study of perspectives of older adults on deintensifying
use with falls and mortality among long-term care residents: a diabetes medications. J Gen Intern Med 2023;38:1008-15.
longitudinal cohort study. BMC Geriatr 2023;23:375. doi:10.1186/ doi:10.1007/s11606-022-07828-3
s12877-023-04096-6 33 Abou J, Crutzen S, Tromp V, et al. Barriers and enablers of healthcare
9 Akazawa M, Imai H, Igarashi A, Tsutani K. Potentially providers to deprescribe cardiometabolic medication in older
inappropriate medication use in elderly Japanese patients. patients: a focus group study. Drugs Aging 2022;39:209-21.
Am J Geriatr Pharmacother 2010;8:146-60. doi:10.1016/j. doi:10.1007/s40266-021-00918-7
amjopharm.2010.03.005 34 Zechmann S, Trueb C, Valeri F, Streit S, Senn O, Neuner-Jehle S.
10 Oliveira MVP, Buarque DC. Polypharmacy and the use of potentially Barriers and enablers for deprescribing among older, multimorbid
inappropriate medications among aged inpatients [Portuguese]. patients with polypharmacy: an explorative study from Switzerland.
Geriatr Gerontol Aging 2018;12:38-44. doi:10.5327/Z2447- BMC Fam Pract 2019;20:64. doi:10.1186/s12875-019-0953-4
211520181800001. 35 Keller MS, Carrascoza-Bolanos J, Breda K, et al. Identifying
11 Clark CM, Shaver AL, Aurelio LA, et al. Potentially Inappropriate barriers and facilitators to deprescribing benzodiazepines and
Medications Are Associated with Increased Healthcare Utilization and sedative hypnotics in the hospital setting using the Theoretical
Costs. J Am Geriatr Soc 2020;68:2542-50. doi:10.1111/jgs.16743 Domains Framework and the Capability, Opportunity, Motivation
12 Kwak MJ, Chang M, Chiadika S, et al. Healthcare expenditure and Behaviour (COM-B) Model: a qualitative study. BMJ
associated with polypharmacy in older adults with cardiovascular Open 2023;13:e066234. doi:10.1136/bmjopen-2022-066234
diseases. Am J Cardiol 2022;169:156-8. doi:10.1016/j. 36 Linsky A, Zimmerman KM. Provider and system-level barriers to
amjcard.2022.01.012 deprescribing: interconnected problems and solutions. Public Policy
13 Schoen C, Davis K, Willink A. Medicare beneficiaries’ high out-of- Aging Rep 2018;28:129-33. doi:10.1093/ppar/pry030
pocket costs: cost burdens by income and health status. Issue Brief 37 Heinrich CH, McHugh S, McCarthy S, Donovan MD. Barriers
(Commonw Fund) 2017;11:1-14. and enablers to deprescribing in long-term care: A qualitative
14 Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate investigation into the opinions of healthcare professionals in Ireland.
polypharmacy: the process of deprescribing. JAMA Intern PLoS One 2022;17:e0274552. doi:10.1371/journal.pone.0274552
Med 2015;175:827-34. doi:10.1001/jamainternmed.2015.0324 38 Ng BJ, Le Couteur DG, Hilmer SN. Deprescribing benzodiazepines
15 Reeve E, Gnjidic D, Long J, Hilmer S. A systematic review of the in older patients: impact of interventions targeting physicians,
emerging definition of ‘deprescribing’ with network analysis: pharmacists, and patients. Drugs Aging 2018;35:493-521.
implications for future research and clinical practice. Br J Clin doi:10.1007/s40266-018-0544-4
Pharmacol 2015;80:1254-68. doi:10.1111/bcp.12732 39 Evrard P, Pétein C, Beuscart JB, Spinewine A. Barriers and enablers
16 Reeve E, Denig P, Hilmer SN, Ter Meulen R. The ethics of deprescribing for deprescribing benzodiazepine receptor agonists in older adults:
in older adults. J Bioeth Inq 2016;13:581-90. doi:10.1007/s11673- a systematic review of qualitative and quantitative studies using
016-9736-y the theoretical domains framework. Implement Sci 2022;17:41.
17 Cadogan CA, Ryan C, Hughes CM. Appropriate polypharmacy doi:10.1186/s13012-022-01206-7
and medicine safety: when many is not too many. Drug 40 Okeowo DA, Zaidi STR, Fylan B, Alldred DP. Barriers and facilitators
Saf 2016;39:109-16. doi:10.1007/s40264-015-0378-5 of implementing proactive deprescribing within primary care: a
18 O’Donnell LK, Ibrahim K. Polypharmacy and deprescribing: systematic review. Int J Pharm Pract 2023;31:126-52. doi:10.1093/
challenging the old and embracing the new. BMC ijpp/riad001
Geriatr 2022;22:734. doi:10.1186/s12877-022-03408-6 41 Weir KR, Ailabouni NJ, Schneider CR, Hilmer SN, Reeve E. Consumer
19 Reeve E, Thompson W, Boyd C, Lundby C, Steinman MA. The state of attitudes towards deprescribing: a systematic review and
deprescribing research: How did we get here?Basic Clin Pharmacol meta-analysis. J Gerontol A Biol Sci Med Sci 2022;77:1020-34.
Toxicol 2023;133:657-60. doi:10.1111/bcpt.13862 doi:10.1093/gerona/glab222

42 Chock YL, Wee YL, Gan SL, Teoh KW, Ng KY, Lee SWH. How willing are 64 McCarthy C, Clyne B, Boland F, et al, SPPiRE Study team. GP-delivered
patients or their caregivers to deprescribe: a systematic review and medication review of polypharmacy, deprescribing, and patient
meta-analysis. J Gen Intern Med 2021;36:3830-40. doi:10.1007/ priorities in older people with multimorbidity in Irish primary
s11606-021-06965-5 care (SPPiRE Study): A cluster randomised controlled trial. PLoS
43 Reeve E, Wolff JL, Skehan M, Bayliss EA, Hilmer SN, Boyd CM. Med 2022;19:e1003862. doi:10.1371/journal.pmed.1003862
Assessment of attitudes toward deprescribing in older medicare 65 Mortsiefer A, Löscher S, Pashutina Y, et al. Family conferences
beneficiaries in the United States. JAMA Intern Med 2018;178:1673- to facilitate deprescribing in older outpatients with frailty
80. doi:10.1001/jamainternmed.2018.4720 and with polypharmacy: the COFRAIL cluster randomized
44 Pharmacy Quality Alliance. PQA Measure Use in CMS’ Part D Quality trial. JAMA Netw Open 2023;6:e234723. doi:10.1001/
Programs. 2011. https://www.pqaalliance.org/medicare-part-d jamanetworkopen.2023.4723
45 Lown Institute. Eliminating Medication Overload: A National 66 van der Meer HG, Wouters H, Pont LG, Taxis K. Reducing the
Action Plan. 2020. https://lowninstitute.org/wp-content/ anticholinergic and sedative load in older patients on polypharmacy
uploads/2020/01/lown-eliminating-medication-overload-web.pdf by pharmacist-led medication review: a randomised controlled trial.
46 Vasilevskis EE, Shah AS, Hollingsworth EK, et al. Deprescribing BMJ Open 2018;8:e019042. doi:10.1136/bmjopen-2017-019042
medications among older adults from end of hospitalization through 67 Mahlknecht A, Wiedermann CJ, Sandri M, et al. Expert-based
postacute care: a Shed-MEDS randomized clinical trial. JAMA Intern medication reviews to reduce polypharmacy in older patients in
Med 2023;183:223-31. doi:10.1001/jamainternmed.2022.6545 primary care: a northern-Italian cluster-randomised controlled trial.
47 Zechmann S, Senn O, Valeri F, et al. Effect of a patient-centred BMC Geriatr 2021;21:659. doi:10.1186/s12877-021-02612-0
deprescribing procedure in older multimorbid patients in 68 Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S.
Swiss primary care - A cluster-randomised clinical trial. BMC Reduction of inappropriate benzodiazepine prescriptions among
Geriatr 2020;20:471. doi:10.1186/s12877-020-01870-8 older adults through direct patient education: the EMPOWER cluster
48 Haag JD, Davis AZ, Hoel RW, et al. Impact of pharmacist-provided randomized trial. JAMA Intern Med 2014;174:890-8. doi:10.1001/
medication therapy management on healthcare quality and jamainternmed.2014.949
utilization in recently discharged elderly patients. Am Health Drug 69 Bayliss EA, Shetterly SM, Drace ML, et al. Deprescribing education
Benefits 2016;9:259-68. vs usual care for patients with cognitive impairment and primary
49 Muth C, Uhlmann L, Haefeli WE, et al. Effectiveness of a complex care clinicians: the OPTIMIZE pragmatic cluster randomized
intervention on Prioritising Multimedication in Multimorbidity trial. JAMA Intern Med 2022;182:534-42. doi:10.1001/
(PRIMUM) in primary care: results of a pragmatic cluster randomised jamainternmed.2022.0502
controlled trial. BMJ Open 2018;8:e017740. doi:10.1136/ 70 Rieckert A, Reeves D, Altiner A, et al. Use of an electronic decision
bmjopen-2017-017740 support tool to reduce polypharmacy in elderly people with chronic
50 Grischott T, Rachamin Y, Senn O, Hug P, Rosemann T, Neuner- diseases: cluster randomised controlled trial. BMJ 2020;369:m1822.
Jehle S. Medication review and enhanced information transfer at doi:10.1136/bmj.m1822
discharge of older patients with polypharmacy: a cluster-randomized 71 Jungo KT, Ansorg AK, Floriani C, et al. Optimising prescribing in
controlled trial in Swiss hospitals. J Gen Intern Med 2023;38:610-8. older adults with multimorbidity and polypharmacy in primary care
doi:10.1007/s11606-022-07728-6 (OPTICA): cluster randomised clinical trial. BMJ 2023;381:e074054.
51 ClinicalTrials.gov. Pharmacist intervention to reduce post- doi:10.1136/bmj-2022-074054
hospitalization utilization. 2023. https://clinicaltrials.gov/ct2/show/ 72 Fried TR, Niehoff KM, Street RL, et al. Effect of the tool to reduce
NCT04071951 inappropriate medications on medication communication and
52 ISRCTN registry. The general practice-based pharmacist: supporting deprescribing. J Am Geriatr Soc 2017;65:2265-71. doi:10.1111/
medicines management in older adults. 2023. https://www.isrctn. jgs.15042
com/ISRCTN18752158 73 Curtin D, Jennings E, Daunt R, et al. Deprescribing in older people
53 2023 American Geriatrics Society Beers Criteria® Update Expert approaching end of life: a randomized controlled trial using STOPPFrail
Panel. American Geriatrics Society 2023 updated AGS Beers criteria. J Am Geriatr Soc 2020;68:762-9. doi:10.1111/jgs.16278
Criteria® for potentially inappropriate medication use in older adults. 74 McDonald EG, Wu PE, Rashidi B, et al. The MedSafer study-electronic
J Am Geriatr Soc 2023;71:2052-81. decision support for deprescribing in hospitalized older adults: a
54 ClinicalTrials.gov. SPIDER: A research & QI collaboration supporting cluster randomized clinical trial. JAMA Intern Med 2022;182:265-73.
practices in improving care for complex elderly patients (SPIDER). doi:10.1001/jamainternmed.2021.7429
2022. https://classic.clinicaltrials.gov/ct2/show/NCT03689049 75 Basger BJ, Moles RJ, Chen TF. Impact of an enhanced pharmacy
55 Greiver M, Dahrouge S, O’Brien P, et al. Improving care for elderly discharge service on prescribing appropriateness criteria: a
patients living with polypharmacy: protocol for a pragmatic cluster randomised controlled trial. Int J Clin Pharm 2015;37:1194-205.
randomized trial in community-based primary care practices in Canada. doi:10.1007/s11096-015-0186-0
Implement Sci 2019;14:55. doi:10.1186/s13012-019-0904-4 76 Olsson IN, Runnamo R, Engfeldt P. Drug treatment in the elderly: an
56 ClinicalTrials.gov. Patient-centred deprescribing of psychotropic, intervention in primary care to enhance prescription quality and
sedative and anticholinergic medication in elderly patients with quality of life. Scand J Prim Health Care 2012;30:3-9. doi:10.3109/0
polypharmacy (PARTNER). 2023. https://classic.clinicaltrials.gov/ct2/ 2813432.2011.629149
show/NCT05842928 77 Kua CH, Yeo CYY, Tan PC, et al. Association of deprescribing
57 ClinicalTrials.gov. Team approach to polypharmacy evaluation and with reduction in mortality and hospitalization: a pragmatic
reduction (TAPER-RCT). 2022. https://classic.clinicaltrials.gov/ct2/ stepped-wedge cluster-randomized controlled trial. J Am Med Dir
show/NCT02942927 Assoc 2021;22:82-89.e3. doi:10.1016/j.jamda.2020.03.012
58 Croke A, Moriarty F, Boland F, et al. Integrating clinical pharmacists 78 Milos V, Rekman E, Bondesson Å, et al. Improving the quality of
within general practice: protocol for a pilot cluster randomised pharmacotherapy in elderly primary care patients through medication
controlled trial. BMJ Open 2021;11:e041541. doi:10.1136/ reviews: a randomised controlled study. Drugs Aging 2013;30:235-
bmjopen-2020-041541 46. doi:10.1007/s40266-013-0057-0
59 ISRCTNregistry. The general practice-based pharmacist: supporting 79 Beuscart JB, Dalleur O, Boland B, et al. Development of a
medicines management in older adults. 2020. https://www.isrctn. core outcome set for medication review in older patients with
com/ISRCTN18752158 multimorbidity and polypharmacy: a study protocol. Clin Interv
60 Lenander C, Elfsson B, Danielsson B, Midlöv P, Hasselström J. Effects Aging 2017;12:1379-89. doi:10.2147/CIA.S135481
of a pharmacist-led structured medication review in primary care on 80 Martin-Kerry J, Taylor J, Scott S, et al. Developing a core outcome set
drug-related problems and hospital admission rates: a randomized for hospital deprescribing trials for older people under the care of a
controlled trial. Scand J Prim Health Care 2014;32:180-6. doi:10.31 geriatrician. Age Ageing 2022;51:afac241. doi:10.1093/ageing/
09/02813432.2014.972062 afac241
61 Jódar-Sánchez F, Malet-Larrea A, Martín JJ, et al. Cost-utility analysis 81 Millar AN, Daffu-O’Reilly A, Hughes CM, et al, CHIPPS Team, University
of a medication review with follow-up service for older adults with of East Anglia. Development of a core outcome set for effectiveness
polypharmacy in community pharmacies in Spain: the conSIGUE trials aimed at optimising prescribing in older adults in care homes.
program. Pharmacoeconomics 2015;33:599-610. doi:10.1007/ Trials 2017;18:175. doi:10.1186/s13063-017-1915-6
s40273-015-0270-2 82 Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump
62 Köberlein-Neu J, Mennemann H, Hamacher S, et al. Interprofessional inhibitors: Evidence-based clinical practice guideline. Can Fam
medication management in patients with multiple morbidities. Dtsch Physician 2017;63:354-64.
Arztebl Int 2016;113:741-8. doi:10.3238/arztebl.2016.0741 83 Farrell B, Black C, Thompson W, et al. Deprescribing
63 Romskaug R, Skovlund E, Straand J, et al. Effect of clinical geriatric antihyperglycemic agents in older persons: Evidence-based clinical
assessments and collaborative medication reviews by geriatrician practice guideline. Can Fam Physician 2017;63:832-43.
and family physician for improving health-related quality of life in 84 Bjerre LM, Farrell B, Hogel M, et al. Deprescribing antipsychotics
home-dwelling older patients receiving polypharmacy: a cluster for behavioural and psychological symptoms of dementia and
randomized clinical trial. JAMA Intern Med 2020;180:181-9. insomnia: Evidence-based clinical practice guideline. Can Fam
doi:10.1001/jamainternmed.2019.5096 Physician 2018;64:17-27.

85 Pottie K, Thompson W, Davies S, et al. Deprescribing benzodiazepine 101 Kojima T, Mizukami K, Tomita N, et al, Working Group on Guidelines
receptor agonists: Evidence-based clinical practice guideline. Can for Medical Treatment and its Safety in the Elderly. Screening Tool
Fam Physician 2018;64:339-51. for Older Persons’ Appropriate Prescriptions for Japanese: Report
86 Reeve E, Farrell B, Thompson W, et al. Evidence-based clinical of the Japan Geriatrics Society Working Group on “Guidelines for
practice guideline for deprescribing cholinesterase inhibitors and medical treatment and its safety in the elderly”. Geriatr Gerontol
memantine: recommendations. The University of Sydney, 2018, Int 2016;16:983-1001. doi:10.1111/ggi.12890
https://cdpc.sydney.edu.au/wp-content/uploads/2019/06/ 102 Holt S, Schmiedl S, Thürmann PA. Potentially inappropriate
deprescribing-recommendations.pdf. medications in the elderly: the PRISCUS list. Dtsch Arztebl
87 deprescribing.org. Deprescribing guidelines and algorithms. 2023. Int 2010;107:543-51. doi:10.3238/arztebl.2010.0543
https://deprescribing.org/resources/deprescribing-guidelines- 103 Renom-Guiteras A, Meyer G, Thürmann PA. The EU(7)-PIM list:
algorithms/ a list of potentially inappropriate medications for older people
88 NSW Therapeutic Advisory Group Inc. Deprescribing tools. 2021. consented by experts from seven European countries. Eur J Clin
https://www.nswtag.org.au/deprescribing-tools/ Pharmacol 2015;71:861-75. doi:10.1007/s00228-015-1860-9
89 Medstopper. Homepage. 2023. https://medstopper.com/ 104 Lavan AH, Gallagher P, Parsons C, O’Mahony D. STOPPFrail (Screening
90 All Wales Medicines Strategy Group. Polypharmacy in older people: Tool of Older Persons Prescriptions in Frail adults with limited life
a guide for healthcare professionals. 2023. https://awttc.nhs. expectancy): consensus validation. Age Ageing 2017;46:600-7.
wales/medicines-optimisation-and-safety/medicines-optimisation- doi:10.1093/ageing/afx005
guidance-resources-and-data/prescribing-guidance/polypharmacy- 105 Van der Linden L, Decoutere L, Flamaing J, et al. Development
in-older-people-a-guide-for-healthcare-professionals/ and validation of the RASP list (Rationalization of Home
91 Hanlon JT, Tjia J. Avoiding adverse drug withdrawal events when Medication by an Adjusted STOPP list in Older Patients): a novel
stopping unnecessary medications according to the STOPPFrail criteria. tool in the management of geriatric polypharmacy. Eur Geriatr
Sr Care Pharm 2021;36:136-41. doi:10.4140/TCP.n.2021.136 Med 2014;5:175-80. doi:10.1016/j.eurger.2013.12.005
92 Hanlon JT, Gray SL. Deprescribing trials: A focus on adverse 106 Rognstad S, Brekke M, Fetveit A, Spigset O, Wyller TB, Straand J.
drug withdrawal events. J Am Geriatr Soc 2022;70:2738-41. The Norwegian General Practice (NORGEP) criteria for assessing
doi:10.1111/jgs.17883 potentially inappropriate prescriptions to elderly patients. A
93 Canadian Medication Appropriateness and Deprescribing Network. modified Delphi study. Scand J Prim Health Care 2009;27:153-9.
Homepage. 2023. https://www.deprescribingnetwork.ca/ doi:10.1080/02813430902992215
94 Australian Deprescribing Network. Homepage. 2023. https://www. 107 Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to
australiandeprescribingnetwork.com.au/ define the functional burden of medications in older people. Arch
95 US Deprescribing Research Network. Homepage. 2023. https:// Intern Med 2007;167:781-7. doi:10.1001/archinte.167.8.781
deprescribingresearch.org/ 108 Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The
96 Network of European Researchers in Deprescribing. Homepage. anticholinergic risk scale and anticholinergic adverse effects in
2023. https://deprescribing.eu/ older persons. Arch Intern Med 2008;168:508-13. doi:10.1001/
97 American Diabetes Association Professional Practice Committee. 13. archinternmed.2007.106
Older adults: standards of medical care in diabetes-2022. Diabetes 109 Hanlon JT, Schmader KE. The medication appropriateness index at
Care 2022;45(Suppl 1):S195-207. doi:10.2337/dc22-S013 20: where it started, where it has been, and where it may be going.
98 Moreno G, Mangione CM, Kimbro L, Vaisberg E, American Geriatrics Drugs Aging 2013;30:893-900. doi:10.1007/s40266-013-0118-4
Society Expert Panel on Care of Older Adults with Diabetes 110 George J, Phun YT, Bailey MJ, Kong DCM, Stewart K. Development
Mellitus. Guidelines abstracted from the American Geriatrics and validation of the medication regimen complexity index. Ann
Society guidelines for improving the care of older adults with Pharmacother 2004;38:1369-76. doi:10.1345/aph.1D479
diabetes mellitus: 2013 update. J Am Geriatr Soc 2013;61:2020-6. 111 National Committee for Quality Assurance. HEDIS MY 2023: See
doi:10.1111/jgs.12514 what’s new, what’s changed and what’s retired. national committee
99 By the 2019 American Geriatrics Society Beers Criteria® Update for quality assurance. 2022. https://www.ncqa.org/blog/hedis-my-
Expert Panel. American Geriatrics Society 2019 updated AGS Beers 2023-see-whats-new-whats-changed-and-whats-retired/
Criteria® for potentially inappropriate medication use in older adults. 112 Centers for Medicare and Medicaid Services. MDS 3.0 quality
J Am Geriatr Soc 2019;67:674-94. doi:10.1111/jgs.15767 measures user’s manual (v16.0). 2023. https://www.cms.gov/files/
100 O’Mahony D, Cherubini A, Guiteras AR, et al. STOPP/START criteria for document/mds-30-qm-users-manual-v160pdf.pdf
potentially inappropriate prescribing in older people: version 3. Eur
Geriatr Med 2023;14:625-32. doi:10.1007/s41999-023-00777-y Web appendix: Supplementary table 1

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Deprescribing in Older Adults

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STATE OF THE ART REVIEW

Deprescribing in older adults with polypharmacy

the bmj | BMJ 2024;385:e074892 | doi: 10.1136/bmj‑2023-074892 1

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Trial Care setting Intervention* Total Key results† Effect of

Medication reviews involving multidisciplinary teams (n=2)

Medication reviews including patient care priorities (n=1)

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Trial Care setting Intervention* Total Key results† Effect of

Deprescribing materials sent to patients (n=2)

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Trial Care setting Intervention* Total Key results† Effect of

Medication reviews (n=2)

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Trial Care setting Intervention* Total Key results† Effect of

key findings from each randomized controlled trial Primary care

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16 care provider would send records to a homecare

recommendations that were sent back to the

Pa ort clin sion are review intervention, the multidisciplinary team

included a geriatrician and a family practitioner who

assessment. This intervention led to a higher mean

health related quality of life (HRQoL) score in the

intervention group versus the control group (p=0.03;

Intervention components primary outcome).63

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successful discontinuation or dose reduction,

Pharmacist/family physician best/worst aspects

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evaluation of deprescribing interventions.

deprescribing interventions over time. Best practices

for successful deprescribing interventions require

targeting provider behavior change, employing

methods to limit contamination effects in trials (eg,

cluster randomized trials), powering studies for

clinically meaningful effect sizes, and emphasizing

longer follow-up periods. These practices contribute

to a more robust understanding of deprescribing

interventions and guide the development of effective

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8 training for healthcare professionals. In the SPIDER

collaboratives and work with quality improvement

trial in Germany targeting patients using ≥1

intervention.56 Firstly, educational material will be

provided for general practitioners and pharmacists

on deprescribing psycholeptics, sedatives, and

anticholinergics, and a moderated interprofessional

patient-reported deprescribing measures, such as

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index,109 and the medication regimen complexity

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measures for Part D prescription drug insurance

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