Measuring Quality of Life in Deprescribing Trials: A Scoping Review.

BACKGROUND: Quality of life (QoL) is an important outcome to capture in clinical trials evaluating deprescribing interventions. OBJECTIVE: We aimed to conduct a scoping review to examine how QoL has been measured in deprescribing trials among older people and identify potentially relevant QoL scales, to better inform QoL measurement in future deprescribing trials. METHODS: We searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, Google Scholar, Epistemonikos, ClinicalTrials.gov, and reference lists of eligible studies (from inception to October 2023). We included randomized and non-randomized comparative studies with a control group that evaluated deprescribing and polypharmacy reduction interventions in people ≥ 65 years of age and measured QoL as an outcome. We also included studies describing the development and validation of QoL scales related to deprescribing, polypharmacy, or medication burden in adults ≥ 18 years of age. Two independent reviewers screened titles and abstracts, then full texts. Two independent reviewers extracted data from 25% of eligible studies in order to verify agreement, then a single reviewer extracted data from the remaining studies, which a second reviewer cross-checked. We critically appraised scales based on the COSMIN checklist. RESULTS: We retrieved 7290 articles, of which 52 were eligible for inclusion, including 44 deprescribing trials and eight scale development studies. From these studies, we found 21 scales that have been used in the context of deprescribing/polypharmacy (12 generic scales used in clinical trials and nine medication-specific scales). Variations of the generic EQ-5D were the most used scales. The measurement properties of scales for capturing changes in QoL from deprescribing were uncertain. Medication-specific QoL scales have not been employed in deprescribing clinical trials and thus, their performance in this context is also not clear. CONCLUSIONS: Several existing QoL scales have been applied to the context of deprescribing/polypharmacy clinical trials, and new scales specific to the problem have been proposed. If deprescribing does impact QoL, our findings suggest it is uncertain whether existing QoL scales can practically and reliably capture such a change or whether any scale is best. However, this review compares various aspects of the scales that researchers and clinicians can consider in decisions about measuring QoL in deprescribing trials, and in planning future research. PROTOCOL REGISTRATION: Open Science Framework: osf.io/aez6w.

Reducing potentially inappropriate polypharmacy at a national and international level: the impact of deprescribing networks.

INTRODUCTION: Over the past decade, polypharmacy has increased dramatically. Measurable harms include falls, fractures, cognitive impairment, and death. The associated costs are massive and contribute substantially to low-value health care. Deprescribing is a promising solution, but there are barriers. Establishing a network to address polypharmacy can help overcome barriers by connecting individuals with an interest and expertise in deprescribing and can act as an important source of motivation and resources. AREAS COVERED: Over the past decade, several deprescribing networks were launched to help tackle polypharmacy, with evidence of individual and collective impact. A network approach has several advantages; it can spark interest, ideas and enthusiasm through information sharing, meetings and conversations with the public, providers, and other key stakeholders. In this special report, the details of how four deprescribing networks were established across the globe are detailed. EXPERT OPINION: Networks create links between people who lead existing and/or budding deprescribing practices and policy initiatives, can influence people with a shared passion for deprescribing, and facilitate sharing of intellectual capital and tools to take initiatives further and strengthen impact.This report should inspire others to establish their own deprescribing networks, a critical step in accelerating a global deprescribing movement.

Polypharmacy and Deprescribing in Older Adults.

Older adults commonly end up on many medications. Deprescribing is an important part of individualizing care for older adults. It is an opportunity to discuss treatment options and revisit medications that may not have been reassessed in many years. A large evidence base exists in the field, suggesting that deprescribing is feasible and safe, though questions remain about the potential clinical benefits. Deprescribing research faces a myriad of challenges, such as identifying and employing the optimal outcome measures. Further, there is uncertainty about which deprescribing approaches are likely to be most effective and in what contexts. Evidence on barriers and facilitators to deprescribing has underscored how deprescribing in routine clinical practice can be complex and challenging. Thus, finding practical, sustainable ways to implement deprescribing is a priority for future research in the field.

Revisiting systematic reviews on deprescribing trials to better inform future practice and research.

Deprescribing aims to address the problem of medication overuse in older adults. There has been an increasing number of systematic reviews of 'deprescribing'. We aimed to describe the categories of trials included in recent systematic reviews, and to make recommendations for future research. We categorized 122 trials included in eight recent deprescribing systematic reviews into: discontinuation, deprescribing implementation, medication optimisation (including medication initiation) and non-initiation trials. We identified heterogeneity and inconsistency in the categories of trials included in deprescribing systematic reviews. For example, 39 trials (32.0%) involved medication initiation in addition to the deprescribing component. It is now time for international researchers to develop and validate terminology used for trials involving discontinuation/deprescribing of medications, and to provide recommendations for evidence synthesis that will better inform future research, and translation into practice and policy.

Prescribing, deprescribing and potential adverse effects of proton pump inhibitors in older patients with multimorbidity: an observational study.

BACKGROUND: Proton pump inhibitors (PPIs) contribute to polypharmacy and are associated with adverse effects. As prospective data on longitudinal patterns of PPI prescribing in older patients with multimorbidity are lacking, we sought to assess patterns of PPI prescribing and deprescribing, as well as the association of PPI use with hospital admissions over 1 year in this population. METHODS: We conducted a prospective, longitudinal cohort study using data from the Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM) trial, a randomized controlled trial testing an intervention to reduce inappropriate prescribing (2016-2018). This trial included adults aged 70 years and older with at least 3 chronic conditions and prescribed at least 5 chronic medications. We assessed prevalence of PPI use at time of hospital admission, and new prescriptions and deprescribing at discharge, and at 2 months and 1 year after discharge, by intervention group. We used a regression with competing risk for death to assess the association of PPI use with readmissions related to their potential adverse effects, and all-cause readmission. RESULTS: Overall, 1080 (57.4%) of 1879 patients (mean age 79 yr) had PPI prescriptions at admission, including 496 (45.9%) patients with a potentially inappropriate indication. At discharge, 133 (24.9%) of 534 patients in the intervention group and 92 (16.8%) of 546 patients in the control group who were using PPIs at admission had deprescribing. Among 680 patients who were not using PPIs at discharge, 47 (14.6%) of 321 patients in the intervention group and 40 (11.1%) of 359 patients in the control group had a PPI started within 2 months. Use of PPIs was associated with all-cause readmission (n = 770, subdistribution hazard ratio 1.31, 95% confidence interval 1.12-1.53). INTERPRETATION: Potentially inappropriate use of PPI, new PPI prescriptions and PPI deprescribing were frequent among older adults with multimorbidity and polypharmacy. These data suggest that persistent PPI use may be associated with clinically important adverse effects in this population.

Factors associated with statin discontinuation near end of life in a Danish primary health care cohort.

BACKGROUND: Long-term preventive treatment such as treatment with statins should be reassessed among patients approaching end of life. The aim of the study was to describe the rate of discontinuation of statin treatment and factors associated with discontinuation in the 6 months before death. METHODS: This study is a retrospective cohort study using national registers and blood test results from primary health care patients. Patients in the Copenhagen municipality, Denmark who died between 1997 and 2018 and were statin users during the 10-year period before death were included. We calculated the proportion who remained statin users in the 6-month period before death. Factors associated with discontinuation were tested using logistic regression. RESULTS: A total of 55,591 decedents were included. More patients continued treatment (64%, n = 35,693) than discontinued (36%, n = 19,898) the last 6 months of life. The 70 and 80 age groups had the lowest odds of discontinuing compared to the 90 (OR 1.59, 95% CI 0.93-2.72) and 100 (OR 3.11, 95% CI 2.79-3.47) age groups. Increasing comorbidity score (OR 0.89, 95% CI 0.87; 0.90 per 1-point increase) and use of statins for secondary prevention (OR 0.89, 95% CI 0.85; 0.93) reduced the likelihood of discontinuation as did a diagnosis of dementia, heart failure, or cancer. CONCLUSION: A substantial portion of patients continued statin treatment near end of life. Efforts to promote rational statin use and discontinuation are required among patients with limited life expectancy, including establishing clear, practical recommendations about statin discontinuation, and initiatives to translate recommendations into clinical practice.

Deprescribing: Moving beyond barriers and facilitators.

Unnecessary polypharmacy continues to be a problem among older adults. The field of deprescribing (planned, supervised process of medication discontinuation) aims to address this problem. Deprescribing is a relatively new field despite having grown substantially in recent years. Much of the early research in this area focused on identifying barriers to and facilitators of deprescribing in clinical practice, which contributed to a large body of work on this topic. However, with continuing research around barriers and facilitators, we need to be mindful to undertake research that builds on existing knowledge, addresses known gaps, and advances the field. Additionally, there is a need in deprescribing research to shift focus to developing ways to address known barriers and harness knowledge of facilitators. That is, translating existing knowledge into strategies and tools that can impact clinical practice and lead to practical and sustained deprescribing efforts.

Patient Preferences for Discussing Life Expectancy: a Systematic Review.

BACKGROUND: Discussing life expectancy helps inform decisions related to preventive medication, screening, and personal care planning. Our aim was to systematically review the literature on patient preferences for discussing life expectancy and to identify predictors for these preferences. METHODS: We searched PubMed, Cochrane Library, Embase, MEDLINE, PsycInfo, and gray literature from inception until 17 February 2021. Two authors screened titles/abstracts and full texts, and extracted data and one author assessed quality. The outcome of interest was the proportion of patients willing to discuss life expectancy. We reported descriptive statistics, performed a narrative synthesis, and explored sub-groups of patients according to patient characteristics. RESULTS: A total of 41 studies with an accumulated population of 27,570 participants were included, comprising quantitative survey/questionnaire studies (n=27) and qualitative interview studies (n=14). Willingness to discuss life expectancy ranged from 19 to 100% (median 61%, interquartile range (IQR) 50-73) across studies, with the majority (77%) reporting more than half of subjects willing to discuss. There was considerable heterogeneity in willingness to discuss life expectancy, even between studies from patients with similar ages, diseases, and cultural profiles. The highest variability in willingness to discuss was found among patients with cancer (range 19-100%, median 61%, IQR 51-81) and patients aged 50-64 years (range 19-97%, median 61%, IQR 45-87). This made it impossible to determine predictors for willingness to discuss life expectancy. DISCUSSION: Most patients are willing to discuss life expectancy; however, a substantial proportion is not. Heterogeneity and variability in preferences make it challenging to identify clear predictors of willingness to discuss. Variability in preferences may to some extent be influenced by age, disease, and cultural differences. These findings highlight the individual and complex nature in which patients approach this topic and stress the importance of clinicians considering eliciting patient's individual preferences when initiating discussions about life expectancy.

Use of sedating medications around nursing home admission in Denmark.

PURPOSE: To examine use of sedating medications around the time of nursing home admission in Denmark. METHODS: We conducted a register-based drug utilization study, describing patterns of commonly used medications with sedative effects leading up to and after nursing home admission using data from 94 Danish nursing homes between 2015 and 2017. RESULTS: We identified 5179 residents (median age 84 years, 63% female) and described monthly incidence and total use of benzodiazepines (BZDs), Z drugs, mirtazapine/mianserin, quetiapine, promethazine, and melatonin. The proportion of unique users of sedating medications was similar before and after admission (42% before vs. 40% after) despite an increase in total use after admission. The overall incidence of sedating medications peaked in the 6 months before and 6 months after admission (peaking at 4.6 per 100 person-months 1 month after admission). The most commonly initiated medications were mirtazapine/mianserin, followed by BZDs and Z drugs. Total use of sedating medications increased leading up to admission (peaking at 1001 defined daily doses per 100 residents per month 1 month after admission) and decreased gradually after admission. CONCLUSIONS: Sedative medication initiation increases sharply leading up to admission in Danish nursing homes. Mirtazapine/mianserin is a commonly used agent in nursing homes, despite limited evidence on benefits and harms. Efforts to promote rational use of these medications in nursing homes remain warranted.

Withdrawal of antihypertensive drugs in older people.

BACKGROUND: Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death. Overall, the use of antihypertensive medications has led to reduction in cardiovascular disease, morbidity rates and mortality rates. However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions, drug-drug interactions and can contribute to increasing medication-related burden. As such, discontinuation of antihypertensives may be considered and appropriate in some older people. OBJECTIVES: To investigate whether withdrawal of antihypertensive medications is feasible, and evaluate the effects of withdrawal of antihypertensive medications on mortality, cardiovascular outcomes, hypertension and quality of life in older people. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2019: the Cochrane Hypertension Specialised Register, CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also conducted reference checking, citation searches and, when appropriate, contacted study authors to identify any additional studies. The searches had no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years and over). Participants were eligible if they lived in the community, residential aged care facilities, or were based in hospital settings. We sought to include trials looking at the complete withdrawal of the antihypertensive medication, and those focusing on a dose reduction of the antihypertensive medicine. DATA COLLECTION AND ANALYSIS: We compared the intervention of discontinuing or reducing antihypertensive medication to usual treatment using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables and we used Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes included: mortality, myocardial infarction, development of adverse drug reactions or adverse drug withdrawal reactions. Secondary outcomes included: blood pressure, hospitalisation, stroke, success of withdrawing from antihypertensives, quality of life, and falls. Two authors independently, and in duplicate, conducted all stages of study selection, data extraction and quality assessment. MAIN RESULTS: Six RCTs met the inclusion criteria and were included in the review (1073 participants). Study duration and follow-up ranged from 4 weeks to 56 weeks. Meta-analysis of studies showed that, in the discontinuation group compared to continuation, the odds for all-cause mortality were 2.08 (95% CI 0.79 to 5.46; low certainty of evidence), for myocardial infarction 1.86 (95% CI 0.19 to 17.98; very low certainty of evidence) and for stroke 1.44 (95% CI 0.25 to 8.35; low certainty of evidence). Blood pressure was higher in the discontinuation group than the continuation group (systolic blood pressure: MD = 9.75 mmHg, 95% CI 7.33 to 12.18; and diastolic blood pressure: MD = 3.5 mmHg, 95% CI 1.82 to 5.18; low certainty of evidence). For the development of adverse events, meta-analysis was not possible; antihypertensive discontinuation did not appear to increase the risk of adverse events and may lead to resolution of adverse drug reactions, although eligible studies had limited reporting of adverse effects of drug withdrawal (very low certainty of evidence). One study reported hospitalisation with an odds ratio of 0.83 for discontinuation compared to continuation (95% CI 0.33 to 2.10; low certainty of evidence). No studies were identified which reported falls. Between 10.5% and 33.3% of participants in the discontinuation group compared to 9% to 15% in the continuation group experienced raised blood pressure or other clinical criteria (as pre-defined by the studies) that would require restarting of therapy/removal from the study. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias). AUTHORS' CONCLUSIONS: There is no evidence of an effect of discontinuing compared with continuing antihypertensives used for hypertension or primary prevention of cardiovascular disease in older adults on all-cause mortality and myocardial infarction. The evidence was low to very low certainty mainly due to small studies and low event rates. These limitations mean that we cannot make any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for use of antihypertensive medications, such as those with frailty, older age groups and those taking polypharmacy, and measure clinically important outcomes such as falls, quality of life and adverse drug events.

Statins in Older Danes: Factors Associated With Discontinuation Over the First 4 Years of Use.

BACKGROUND AND OBJECTIVE: Use of statins is considerable among older persons. We investigated factors associated with statin discontinuation in new statin users aged 70 years or older within the first 4 years of use. DESIGN: Register-based descriptive drug utilization study using data from 2008 to 2016. POPULATION/SETTING: All Danish persons, aged 70 years or older, initiating statin treatment. MEASUREMENTS: Rates and predictors of statin discontinuation after 1 year (early), 2 years, and 4 years. Predictors of discontinuation were estimated using logistic regression. RESULTS: We included 83 788 statin initiators. At 1 year, 13% had discontinued their treatment, while another 12% and 13% discontinued after 2 and 4 years, respectively. The overall discontinuation rate over 4 years was 32%. Increasing age was associated with discontinuation at all time points (adjusted odds ratio [OR] = 2.06 [95% confidence interval {CI} = 1.35-3.16] at 1 year, adjusted OR = 3.94 [95% CI, 1.83-8.49] at 4 years, comparing those aged >95 years to those aged 70-74 years). Further, higher comorbidity scores and use of more than 10 medications were modestly associated with discontinuation. Use of statins for secondary prevention was associated with decreased odds of discontinuation compared to primary prevention at 1 year (adjusted OR = 0.74; 95% CI, 0.65-0.83) and at 4 years (adjusted OR = 0.83; 95% CI, 0.72-0.95), along with concomitant use of cardiovascular (CV) therapies. The annual proportion of early discontinuers ranged from 14% to 17% for primary prevention and from 9% to 12% for secondary prevention between 2008 and 2015. DISCUSSION: Statin discontinuation within the first 4 years after initiation appeared to be influenced most strongly by age, and may also be influenced by comorbidity, polypharmacy, use for secondary prevention, and concomitant CV medication use. Future research should clarify reasons for, and discussions about, statin discontinuation and initiation among older persons, to provide additional insight on this topic. J Am Geriatr Soc 67:2050-2057, 2019.

Deprescribing guidelines: An international symposium on development, implementation, research and health professional education.

Deprescribing is a clinically important and feasible innovation that ensures medication efficacy, reduces harms, and mitigates polypharmacy. It involves reducing doses or stopping medications that are not useful, no longer needed, or which may be causing harm. It may also involve changing to a safer agent or using non-pharmacological approaches for care instead. Clinical guidelines combined with behaviour changes (of health care providers (HCPs), the public, and health care decision-makers) are needed to integrate deprescribing into routine practice. Using rigorous international standards, the Bruyère Research Institute Deprescribing Guidelines research team validated a ground-breaking deprescribing guideline methodology and developed or co-developed 5 evidence-based deprescribing guidelines. In March 2018, the team hosted an international symposium convening HCPs, researchers, public agencies, policymakers, and patient advocates in Ottawa, Ontario, Canada. This 3-day symposium aimed to facilitate knowledge exchange amongst guideline developers, users, and the public; initiate partnerships and collaborations for new deprescribing guideline recommendations and effectiveness research; and to continue work on HCP deprescribing education activities. An interprofessional planning committee developed an overall agenda, and small groups worked on session objectives and formats for different components: methods for rigorous deprescribing guideline development, implementation experiences, research/evaluation experiences and educational needs. Through a series of keynote speakers, panel discussions, and small working groups, the symposium provided a forum for participants to meet one another, learn about their different experiences with deprescribing guidelines, and develop collaborations for future initiatives. One hundred thirty participants, from 10 countries and representing over 100 institutions and organizations took part. Symposium proceedings are presented in this issue of RSAP for sharing with the wider community engaged in the care of patients with problematic polypharmacy.

Deprescribing: Future directions for research.

A World Café workshop was held at the Bruyère Evidence-Based Deprescribing Guidelines Symposium in March 2018 with 30 participants (researchers, clinicians, policy makers, stakeholders). This workshop explored priorities for future work in the field of deprescribing and deprescribing guidelines through group discussion. The discussions were guided by the following questions: (1) What are deprescribing research priorities (to inform guideline development), (2) What outcome measures are important for developing deprescribing guidelines, and (3) How do we evaluate the implementation and effectiveness of deprescribing guidelines? Discussion from all 3 questions identified 6 main priority areas: (1) conducting high-quality and long-term clinical trials that measure patient-important outcomes, (2) focusing on patient involvement and perspectives, (3) investigating the pharmacoeconomics of deprescribing interventions, (4) understanding deprescribing interventions in different populations, (5) generating evidence on clinical management during deprescribing (e.g. managing adverse drug withdrawal effects, subsequent re-prescribing), and (6) implementing interventions in clinical practice. These topics represent what a group of experienced researchers, clinicians, and stakeholders in the field collectively felt was important to consider for design and implementation of future deprescribing studies. The aim is for these findings to stimulate future discussions and be considered by granting agencies, policy makers, deprescribing research networks, and individual researchers planning future deprescribing studies.

Health care providers' roles and responsibilities in management of polypharmacy: Results of a modified Delphi.

BACKGROUND: Little is known about the roles that allow interprofessional teams to effectively manage older patients experiencing polypharmacy. OBJECTIVES: To identify and examine the consensus on salient interprofessional roles, responsibilities and competencies required in managing polypharmacy. METHODS: Four focus groups with 35 team members practising in geriatrics were generated to inform survey development. The sessions generated 63 competencies, roles or responsibilities, which were categorized into 4 domains defined by the Canadian Interprofessional Health Collaborative. The resulting survey was administered nationally to geriatric health care professionals who were asked to rate the importance of each item in managing polypharmacy; we sought agreement within and across professions using a confirmatory 2-round Delphi method. RESULTS: Round 1 was completed by 98 survey respondents and round 2 by 72. There was high intra-professional and interprofessional consensus regarding the importance of competencies among physicians, nurses and pharmacists; though pharmacists rated fewer competencies as important. Less consensus was observed among other health care professionals or they indicated the nonimportance of competencies despite focus group discussion to the contrary. DISCUSSION: Although there is a strong consensus of polypharmacy management competencies across team members who have been more traditionally involved in medication management, there continue to be health care providers with differing understandings of competencies that may contribute to reduced reliance on medication. Lower importance ratings suggest pharmacists may not acknowledge or recognize their own potential roles in interprofessional polypharmacy management. CONCLUSION: Further exploration to understand the underutilization of professional expertise in managing polypharmacy will contribute to refining role clarity and translating competencies in practical settings, as well as guiding educators regarding curricular content.

Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper or stop proton pump inhibitors (PPIs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: Five health professionals (1 family physician, 3 pharmacists, and 1 gastroenterologist) and 5 nonvoting members comprised the overall team; members disclosed conflicts of interest. The guideline process included the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, with a detailed evidence review in in-person, telephone, and online meetings. Uniquely, the guideline development process included a systematic review of PPI deprescribing trials and examination of reviews of the harm of continued PPI use. Narrative syntheses of patient preferences and resource-implication literature informed recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and then to health care professional associations for review and revisions made at each stage. A decision-support algorithm was developed in conjunction with the guideline. RECOMMENDATIONS: This guideline recommends deprescribing PPIs (reducing dose, stopping, or using "on-demand" dosing) in adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or mild to moderate gastroesophageal reflux disease or esophagitis, and whose symptoms are resolved. The recommendations do not apply to those who have or have had Barrett esophagus, severe esophagitis grade C or D, or documented history of bleeding gastrointestinal ulcers. CONCLUSION: This guideline provides practical recommendations for making decisions about when and how to reduce the dose of or stop PPIs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Deprescribing versus continuation of chronic proton pump inhibitor use in adults.

BACKGROUND: Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). OBJECTIVES: To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS: The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. AUTHORS' CONCLUSIONS: In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.

Deprescribing: A narrative review of the evidence and practical recommendations for recognizing opportunities and taking action.

Deprescribing can be defined as the process of withdrawal or dose reduction of medications which are considered inappropriate in an individual. The aim of this narrative review is to provide an overview of "deprescribing"; firstly discussing the potential benefits and harms followed by the barriers to and enablers of deprescribing. We also provide practical recommendations to recognise opportunities and strategies for deprescribing in practice. Studies focused on minimizing polypharmacy indicate that deprescribing may be associated with potential benefits including resolution of adverse drug reactions, improved quality of life and medication adherence and a reduction in drug costs. While the data on the benefits is inconsistent, deprescribing appears to be safe. There are, however, potential harms including return of medical conditions or symptoms and adverse drug withdrawal reactions which emphasise the need for the process to be supervised and monitored by a health care professional. Taking action on deprescribing can be facilitated by knowledge of potential barriers, implementing a deprescribing process (utilising developed tools and resources) and identifying opportunities for deprescribing through engaging with patients and caregivers and other health care professionals and considering deprescribing in a variety of populations. Important areas for future research include the suitability of deprescribing of certain medications in specific populations, how to implement deprescribing processes into clinical care in a feasible and cost effective manner and how to engage consumers throughout the process to achieve positive health and quality of life outcomes.