Reducing Adverse Drug Events in Older Adults

Tara R. Earl; Nicole D. Katapodis; Stephanie R. Schneiderman

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Hall KK, Shoemaker-Hunt S, Hoffman L, et al. Making Healthcare Safer III: A Critical Analysis of Existing and Emerging Patient Safety Practices [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 Mar.

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Making Healthcare Safer III: A Critical Analysis of Existing and Emerging Patient Safety Practices [Internet].

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9Reducing Adverse Drug Events in Older Adults

Tara R. Earl, Ph.D., M.S.W., Nicole D. Katapodis, M.P.H., and Stephanie R. Schneiderman, M.P.P.

Introduction

Background

People are living longer than ever. In the United States, the number of Americans age 65 years and older increased from 37.2 million in 2006 to 49.2 million in 2016 (33% increase) and is projected to reach 98 million by 2060.¹ With age comes the likelihood of increasing morbidity. An estimated 98 percent of people age 65 years and older have at least two chronic diseases and take at least five prescription medications.²

As the medical field develops clinical therapies, protocols, and treatments to help the elderly population better manage, prevent, and/or enhance quality of life, there are also risks. For instance, polypharmacy—taking multiple medications concurrently—and the use of potentially inappropriate medicines (PIMs) pose the greatest risk of drug-related adverse drug events (ADEs) for older adults, who are more likely than younger people to take multiple medications at the same time.³^,⁴ Broadly defined as injuries that result from drug-related medical interventions (e.g., medication errors, adverse drug reactions, allergic reactions, or overdoses), ADEs have been associated with thousands of visits to the emergency department (ED) and hospitalizations.⁵ However, up to half of identified ADEs are preventable,⁶ and ADEs are one of the most common types of preventable adverse events across all healthcare settings.⁷

Importance of Harm Area

Common consequences of ADEs include drug-related morbidity and mortality, heart and/or renal failure, gastrointestinal and internal bleeding, and negative drug-drug interactions.⁸^,⁹ Given the prevalence of ADEs, preventing them is an important public health priority. The Joint Commission’s 2019 revised National Patient Safety Goals on anticoagulant medicines identifies ADE prevention—in both hospital and ambulatory clinic settings—as a primary objective.⁶^,¹⁰ In addition to potential harm to patients, the estimated cost of treating ADEs in hospital settings was more than $76 billion in 2014 and has likely increased since.¹¹^,¹²

References for Introduction

1.: Administration for Community Living. 2017 Profile of Older Adults.Washington, DC.: Administration for Community Living; 2019. https://acl.gov/sites/default/files/Aging%20and%20Disability%20in%20America/2017OlderAmericansProfile.pdf.
2.: National Center for Health Statistics. Health, United States. Health, United States, 2016: With Chartbook on Long-term Trends in Health. Hyattsville, MD: National Center for Health Statistics; 2017. [PubMed: 28910066]
3.: Classen DC, Jaser L, Budnitz DS. Adverse drug events among hospitalized Medicare patients: epidemiology and national estimates from a new approach to surveillance. Jt Comm J Qual Patient Saf. 2010;36(1):12–21.10.1016/s1553-7250(10)36003-x. [PubMed: 20112660] [CrossRef]
4.: Cousins D, Rosario C, Scarpello J. Insulin, hospitals and harm: a review of patient safety incidents reported to the National Patient Safety Agency. Clin Med (Lond). 2011;11(1):28–30.10.7861/clinmedicine.11-1-28. [PMC free article: PMC5873796] [PubMed: 21404780] [CrossRef]
5.: Agency for Healthcare Research and Quality. Patient Safety Primer: Medication Errors and Adverse Drug Events https://psnet.ahrq.gov/primer/medication-errors-and-adverse-drug-events. Accessed November 7, 2019.
6.: Office of Disease Prevention and Health Promotion. National Action Plan for Adverse Drug Event Prevention.Washington, DC: U.S. Department of Health and Human Services; 2014. https://health.gov/hcq/pdfs/ADE-Action-Plan-508c.pdf.
7.: Institute of Medicine Committee on Quality of Health Care in A. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academies Press; 2001. [PubMed: 25057539]
8.: Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015;11:1061–75.10.2147/tcrm.S79135. [PMC free article: PMC4508078] [PubMed: 26203254] [CrossRef]
9.: Sultana J, Cutroneo P, Trifiro G. Clinical and economic burden of adverse drug reactions. J Pharmacol Pharmacother. 2013;4:(Suppl 1):S73–7.10.4103/0976-500x.120957. [PMC free article: PMC3853675] [PubMed: 24347988] [CrossRef]
10.: The Joint Comission. 2019 Patient Safety Goals. https://www.jointcommission.org/assets/1/6/2019_HAP_NPSGs_final2.pdf. Accessed November 11, 2019.
11.: Johnson JA, Bootman JL. Drug-related morbidity and mortality. A cost-of-illness model. Arch Intern Med. 1995;155(18):1949–56 [PubMed: 7575048]
12.: Weiss A, Freeman W, Heslin K, et al. Adverse Drug Events in U.S. Hospitals, 2010 Versus 2014.Rockville, MD: Agency for Healthcare Research and Quality; 2018. https://psnet.ahrq.gov/issue/adverse-drug-events-us-hospitals-2010-versus-2014.

9.1. Reducing ADEs in Older Adults

This chapter summarizes articles published from 2008 to 2018 that describe strategies that effectively reduce ADEs in older adults. Across all studies, the targeted population was adults aged 65 years and older, and the desired outcome was reduced inappropriate medication use or polypharmacy. We describe two approaches that inform how best to identify inappropriate medicines and reduce ADEs. We then describe our literature review strategy and conclude by identifying potential gaps, challenges, and future directions to consider in this field. Resources for future implementation efforts are also included.

9.1.1. Practice Description

PSP Overview

Deprescribing

Setting(s): acute hospital care, ambulatory care (primary care, long-term care, residential aged care facilities, skilled nursing facilities), community pharmacies
Patient Population Targets: older adults, patients at high risk for polypharmacy and comorbidities
Provider Targets: clinical community pharmacists, hospital pharmacists, geriatricians, general practitioners, geriatric nurse practitioners

STOPP Criteria

Settings: acute hospital care, ambulatory care (home care, long-term care, skilled nursing facilities)
Patient Population Target: adults aged 65 or older taking multiple medications
Provider Targets: geriatricians, general practitioners, pharmacists, prescribing physicians

Polypharmacy and the use of inappropriate medications present a risk for ADEs. Driven by the need to identify the most precise way to identify ineffective and/or unnecessary medications, several intervention strategies report varied success in implementation and effectiveness. As described in the overview box to the right, this review focuses on two emerging approaches: (1) deprescribing to reduce polypharmacy and (2) the use of the Screening Tool of Older Person’s inappropriate Prescriptions (STOPP) criteria to reduce PIMs. Deprescribing involves reducing doses or stopping medications that are not useful or are no longer needed in order to reduce polypharmacy, reduce harm, and improve health. STOPP is a validated, evidence-based list of 80 criteria for potentially inappropriate prescribing in older adults, first published in 2008 and revised in 2014. The box to the right provides an overview.

While it is a fairly new tool, evidence suggests that STOPP may be better at predicting PIMs in older adults than other tools, such as the American Geriatrics Society’s Beers Criteria^®, hereafter referred to as the Beers Criteria.¹ While this patient safety practice (PSP) specifically emphasizes the use of the STOPP criteria, it is often used with a companion screener, the Screening Tool to Alert to Right Treatment (START). START includes a set of 34 evidence-based and validated prescribing indicators for common diseases for the same population. Both have been more commonly used in non-U.S. settings. For the purposes of this review, we focus on STOPP and reference START as appropriate.

9.1.2. Methods

This section describes the literature search and review methods specific to this PSP area. The general methodology used across the project is available in the methods chapter of this report.

We applied search terms in two databases (CINAHL^®) and MEDLINE^®). Terms used to find deprescribing literature included “deprescribing,” “adverse reactions/PC,” “adverse drug events,” “drug-related side effects,” “inappropriate prescribing/PC,” “polypharmacy,” “polymedication,” “cessation,” “discontinuation,” and “withdrawal.” The search terms for STOPP included “STOPP,” “potentially inappropriate medication list,” “research studies,” “prepost,” “interventional,” “randomized,” and “non-randomized.” We further refined each search to focus on the priority population by including “older adult,” “aged,” “senior,” and “elderly.”

To make sure we identified all relevant articles, we reviewed the reference lists of systematic literature review articles and read abstracts or full-text of apparently relevant articles to screen them for inclusion.

Methods prescribed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines guided the review. PRISMA flow diagrams illustrate the process for both the deprescribing and STOPP searches. Overall, 988 publications were identified and 131 articles were considered eligible for further review. Priority was given to intervention studies as opposed to prevalence, incidence, or observational studies. Studies were included if they were published in English; explicitly focused on deprescribing, polypharmacy, PIMs, and/or STOPP; targeted older adults; and effectively (i.e., statistically significantly) reduced medication use as a result of implementing an intervention related to deprescribing and/or using the STOPP criteria. Articles were excluded if the focus was on children/pediatric care. Ultimately, we selected for the evidence summary the 27 studies that are listed in alphabetical order in the evidence tables.

General methods for this report are described in the Methods section of the full report.

For this patient safety practice, a PRISMA flow diagram and evidence table, along with literature-search strategy and search-term details, are included in the report appendixes A through C.

9.1.3. Review of Evidence for Reducing ADEs in Older Adults

This section presents evidence from the 27 studies we reviewed related to the use of deprescribing or using the STOPP criteria to reduce the unnecessary medications that could lead to ADEs in older adults. It is important to note that deprescribing and the STOPP criteria are not actual interventions. Rather, deprescribing is an approach and STOPP is a screening tool. The evidence in this section specifically highlights intervention studies as opposed to prevalence, observational, or incidence studies.

Reference for Section 9.1

1.: Hamilton H, Gallagher P, Ryan C, Byrne S, O’Mahony D. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med. 2011;171(11):1013–9.10.1001/archinternmed.2011.215. [PubMed: 21670370] [CrossRef]

9.2. Patient Safety Practice: Deprescribing To Reduce Polypharmacy in Older Adults

9.2.1. Clinical Outcomes

Key Findings

Geriatrician and clinical pharmacist reviews can effectively reduce the use of unnecessary medications.
Educating patients and their families helps them better communicate their medication use to providers in order to discontinue unnecessary medications.
Deprescribing reduces medication-related costs for patients and healthcare systems.

As previously discussed, deprescribing addresses polypharmacy by reducing inappropriate prescriptions and can lead to improved clinical outcomes. However, clinical outcomes can vary with the specific approach to deprescribing. Ocampo et al. (2015) found that a pharmacist-led medication review with an 18-month follow-up period in community pharmacies identified 408 negative outcomes related to prescriptions and resolved 393 of these problems, resulting in a significant decrease in hospitalizations (p=0.039) and ED visits (p=0.001). Physical and mental health summary scales increased from 65.8 to 82.7 (p<0.0001) and 66.2 to 81.1 (p<0.0001), respectively, while patients who were nonadherent decreased from 68 to 1 (p<0.0001).¹ Others reported that discontinuing multiple medications simultaneously was significantly associated with reductions in both the number of reported falls and frailty scores for older adults.² These researchers also examined collaborative medication reviews with general practitioners of patients age 65 years and older in a residential care facility. Their study noted a significant reduction in drug burden index scores, by 0.34 (p<0.001), reflecting a decrease in the cumulative exposure to medications, and the number of falls and frailty measured using the Edmonton frailty scale dropped by a mean difference of 1.35 (p<0.05). Additionally, the number of adverse drug reactions decreased by 4.24 (p<0.05) after 6 months.² However, in a multidisciplinary geriatric specialist medication review panel intervention including registrars in geriatric medicine, hospital pharmacists, and geriatric nurse practitioners, no significant difference was found in mortality (p=0.226) or frequency of hospital transfers (p=0.213) between intervention and regular care groups.³ A summary of key findings are located in the Key Findings box above.

9.2.1.1. Process Outcomes

Many studies focused on process-related outcomes such as a decrease in the number of medications prescribed, which is expected to lead to clinical outcomes. Findings from the studies are subsequently presented by topical area.

9.2.1.1.1. Protocols, Algorithms, and Clinical Decision Support Systems

Among the studies focusing on the use of protocols, algorithms, and clinical decision support systems to promote deprescribing, patients had a significant decrease in the number of medications prescribed. A patient-centered deprescribing protocol called Shed-MEDS is implemented in four phases: (1) confirm medication history and list, (2) evaluate medication for deprescribing, (3) decide with the patients, (4) synthesize and communicate recommendations. Petersen et al. (2018) found that, among Medicare beneficiaries prescribed five or more medications, the mean number of prescribed medications was significantly reduced, from 11.6 to 9.1 (p=0.032), for those receiving the protocol.⁴ Garfinkel et al. (2010) worked with elderly patients in Israel to implement the Good Palliative-Geriatric Practice algorithm, an evidence-based flow chart for drug discontinuation, which recommended discontinuing a total of 311 medications for 64 patients.⁵ McKean et al. (2016) worked with patients age 65 or older taking eight or more medications to implement an intervention consisting of a formal medication review among rounding clinicians, followed by receipt of a paper-based or computerized form listing clinical and medication data linked with a five-step clinical decision support tool to determine drugs eligible for discontinuation. The intervention led to a 34.3-percent decrease in regular medications, a small but nonsignificant decrease in PRN (as needed) medications, and a significant decrease in the number of medications per patient at discharge compared with admission (median change: 7 vs. 10 medications [p<0.001]).⁶

9.2.1.1.2. Interventions

Education-improvement interventions, which directly educate consumers, have also been associated with medication discontinuation to reduce polypharmacy. Tannenbaum et al. (2014) found that a direct-to-consumer education intervention using an 8-page booklet to describe the risks of benzodiazepine use and a step-wise tapering protocol led to a 27 percent discontinuation of benzodiazepines among community pharmacy patients age 65 or older in the intervention group, compared with 5 percent in the control group (95% confidence interval [CI], 14% to 32%), at 6 months after the intervention.⁷ Martin et al. (2018) studied a consumer-based education intervention led by pharmacists in community pharmacies providing an educational brochure to patients age 65 and older. The study resulted in 43 percent of the intervention group no longer filling inappropriate medications, compared with 12 percent of the control group (95% CI, 23% to 38%).⁸

9.2.1.1.3. Pharmacist-Led Medication Reviews

Pharmacist-led medication review interventions across a number of settings have also promoted deprescribing. Lenander et al. (2014) found that a pharmacist-led medication review in a primary care setting targeting patients 65 and older with five or more different medications led to a decrease in drug-related problems. Using the Beers Criteria, after 12 months, drug-related problems decreased for the intervention group from 1.73 to 1.31 (p<0.05). There was also a larger reduction in the number of drugs prescribed in the intervention group (p<0.046).⁹ Veggeland and Dyb (2008) observed the effect of adding a clinical pharmacist performing medication reviews to a geriatric care hospital team, finding it led to improved medication changes, extensive discontinuation of drugs, dose reductions, or decisions to revise medications at a later stage of hospitalization.¹⁰

9.2.1.1.4. Clinician-Led Medication Reviews

We found one study of a clinician-led medication review. Tamura and colleagues (2011) worked with geriatric medicine fellows in a nursing facility to implement a medication review using the updated Beers Criteria for patients (average age: 83 years old) with nine or more medications, leading to an average reduction of total medications from 16.64 to 15.53 (p<0.001), average number of scheduled medications from 11.3 to 10.99 (p<0.001), average number of PRN medications from 5.33 to 4.56 (p<0.001), and average number of high-risk medications from 5.33 to 4.56 (p<0.001).¹¹

9.2.1.1.5. Pharmacist and Clinician Medication Reviews

Medication reviews involving both pharmacists and clinicians effectively decreased medication use in two studies. Chan and others (2014) determined the effectiveness of a medications safety review clinic for geriatric outpatients age 65 or older who were prescribed eight or more chronic medications or who had visited at least three different physicians at the two participating hospitals within 3 months. Four medication review sessions were performed by two research assistants, one clinical pharmacist, and one geriatrician, leading to a mean decrease in chronic medications from 9.0 to 8.6 (p<0.05).¹² Wouters et al. (2017) sought to improve prescribing in nursing home residents by implementing the Multidisciplinary Multistep Medication Review, also referred to as the 3MR intervention. The randomized controlled trial took place on nursing home wards and consisted of an evaluation of the patient’s perspective, medical history, and use of medications; a meeting between the physician and pharmacist; and the execution of medication changes. Results showed that successful discontinuation, without relapse or severe withdrawal symptoms, of at least one inappropriate medication was greater in the intervention group than the control group (39.1% vs. 29.5%; 95% CI, 1.02 to 1.75). In the 4 months after the baseline assessment, there was no deterioration of clinical outcomes, such as neuropsychiatric symptoms, cognitive function, or quality of life, in either group.¹³

9.2.1.2. Economic Outcomes

One study assessed the economic impact of deprescribing. Kojima et al. (2012) evaluated the effect on medication costs of a physician intervention using two tools, the Beers Criteria and the Epocrates online drug-drug interaction program, to reduce polypharmacy among long-term care residents. Findings showed that residents undergoing the intervention had significantly lower health care costs after the intervention. Average monthly medication costs declined from $874 to $843 (p<0.0001), scheduled medication costs from $814 to $801 (p=0.007), PRN medication costs from $60 to $42 (p<0.0001), and nursing medication administration costs from $483 to $461 (p<0.0001).¹⁴

References for Section 9.2

1.: Ocampo CC, Garcia-Cardenas V, Martinez-Martinez F, et al. Implementation of medication review with follow-up in a Spanish community pharmacy and its achieved outcomes. Int J Clin Pharm. 2015;37(5):931–40.10.1007/s11096-015-0145-9. [PubMed: 26040837] [CrossRef]
2.: Ailabouni N, Mangin D, Nishtala PS. DEFEAT-polypharmacy: deprescribing anticholinergic and sedative medicines feasibility trial in residential aged care facilities. Int J Clin Pharm. 2019;41(1):167–78.10.1007/s11096-019-00784-9. [PubMed: 30659492] [CrossRef]
3.: Pope G, Wall N, Peters CM, et al. Specialist medication review does not benefit short-term outcomes and net costs in continuing-care patients. Age Ageing. 2011;40(3):307–12.10.1093/ageing/afq095. [PubMed: 20817937] [CrossRef]
4.: Petersen AW, Shah AS, Simmons SF, et al. Shed-MEDS: pilot of a patient-centered deprescribing framework reduces medications in hospitalized older adults being transferred to inpatient postacute care. Ther Adv Drug Saf. 2018;9(9):523–33.10.1177/2042098618781524. [PMC free article: PMC6116773] [PubMed: 30181860] [CrossRef]
5.: Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy. Arch Intern Med. 2010;170(18):1648–54.10.1001/archinternmed.2010.355. [PubMed: 20937924] [CrossRef]
6.: McKean M, Pillans P, Scott IA. A medication review and deprescribing method for hospitalised older patients receiving multiple medications. Intern Med J. 2016;46(1):35–42.10.1111/imj.12906. [PubMed: 26387783] [CrossRef]
7.: Tannenbaum C, Martin P, Tamblyn R, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. J Am Med Assoc Intern Med. 2014;174(6):890–8.10.1001/jamainternmed.2014.949. [PubMed: 24733354] [CrossRef]
8.: Martin P, Tamblyn R, Benedetti A, et al. Effect of a Pparmacist-Led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. J Am Med Assoc. 2018;320(18):1889–98.10.1001/jama.2018.16131. [PMC free article: PMC6248132] [PubMed: 30422193] [CrossRef]
9.: Lenander C, Elfsson B, Danielsson B, et al. Effects of a pharmacist-led structured medication review in primary care on drug-related problems and hospital admission rates: a randomized controlled trial. Scand J Prim Health Care. 2014;32(4):180–6.10.3109/02813432.2014.972062. [PMC free article: PMC4278387] [PubMed: 25347723] [CrossRef]
10.: Veggeland T, Dyb S. The contribution of a clinical pharmacist to the improvement of medication at a geriatric hospital unit in Norway. Pharm Pract (Granada). 2008;6(1):20–4.PMID: 25170361 [PMC free article: PMC4147275] [PubMed: 25170361]
11.: Tamura BK, Bell CL, Lubimir K, et al. Physician intervention for medication reduction in a nursing home: the polypharmacy outcomes project. J Am Med Dir Assoc. 2011;12(5):326–30.10.1016/j.jamda.2010.08.013. [PMC free article: PMC3102122] [PubMed: 21450207] [CrossRef]
12.: Chan DC, Chen JH, Wen CJ, Chiu LS, Wu SC. Effectiveness of the medication safety review clinics for older adults prescribed multiple medications. J Formos Med Assoc. 2014;113(2):106–13.10.1016/j.jfma.2012.04.013. [PubMed: 24530244] [CrossRef]
13.: Wouters H, Scheper J, Koning H, et al. Discontinuing Inappropriate Medication Use in Nursing Home Residents: A Cluster Randomized Controlled Trial. Ann Intern Med. 2017;167(9):609–17.10.7326/m16-2729. [PubMed: 29052691] [CrossRef]
14.: Kojima G, Bell C, Tamura B, et al. Reducing cost by reducing polypharmacy: the polypharmacy outcomes project. J Am Med Dir Assoc. 2012;13(9):818.e11–5.10.1016/j.jamda.2012.07.019. [PMC free article: PMC3489959] [PubMed: 22959733] [CrossRef]

9.3. Patient Safety Practice: Using the STOPP Criteria To Reduce the Use of PIMs in Older Adults

9.3.1. Clinical Outcomes

The studies evaluating STOPP did not focus on clinical outcomes. There has been more emphasis on assessing the process of implementing or using STOPP criteria to more accurately identify PIMs.

9.3.2. Process Outcomes

Four studies demonstrate the effectiveness of STOPP. Campins et al. (2017) reported that the STOPP tool helped pharmacists determine that 27 percent of the intervention population’s prescriptions were potentially inappropriate. The majority of these prescriptions were then changed, as follows: 43 percent were discontinued, 33 percent received a dose adjustment, 14 percent were substituted for more appropriate medications, and for 10 percent, the patient received a new prescription.¹ Similarly, Gibert et al. (2018) used STOPP in primary care consultations in France, resulting in a 38-percent reduction in the number of PIMs (n=170 vs. 106) across about 45 percent of patients (n=44) (p<0.001).² Hannou et al. (2017) introduced a part-time ward-based clinical pharmacist to a psychiatric unit’s multidisciplinary team and screened prescriptions for potentially inappropriate drug prescribing (PIDP) using the STOPP/START criteria. The intervention was measured by the acceptance rate of pharmacist interventions (PhIs).The global PhI acceptance rate was 68 percent and the rate based on STOPP/START was 47%. When two STOPP criteria, the prescription of benzodiazepines or of neuroleptic drugs to patients who had fallen in the last 3 months, were removed from analysis, the acceptance rate for STOPP/START-based PhIs increased to 67 percent.³ In Ilic et al. (2015), an education intervention targeting both physicians and nursing home residents provided information about the START/STOPP and Beers Criteria, as well as adherence, adverse drug reactions, and drug-drug interactions. According to the STOPP criteria, 70 drugs were inappropriately prescribed before the intervention, and 20 drugs after 6 months. The median number of inappropriately prescribed drugs according to the STOPP criteria before education was 3.5 (range 1.0–20.0), and the median number after education was 1.5 (range 0.0–6.0; Z=2.823; p<0.005).⁴

9.3.3. Economic Outcomes

STOPP has the potential for positive economic outcomes. After implementing a comprehensive geriatric assessment (CGA) that included the STOPP criteria, Unutmaz et al. (2018) suggested that the tool saved patients about $13 per month in medication costs, as well as reducing polypharmacy, PIMs, and potential prescribing omissions (PPOs).⁵ O’Connor et al. (2016) reported significant reductions in medication costs. At discharge, median medication cost was significantly lower in the intervention group than in the control group (p<0.001).⁶ Frankenthal et al. (2017) found that when pharmacists and prescribing physicians discussed medication reviews rather than communicating in writing, the reviews were more effective. Furthermore, the authors reported that the costs of medications were significantly lower in the intervention group than the control group (p<0.001) at the 24-month followup.⁷ Hill-Taylor et al. reviewed three studies on the direct costs of potentially inappropriate prescribing (PIP). One study, Barry et al., found that the wholesale cost of the PPO instances identified by the START criteria in their study population was €188 per patient per year in 2007. Another, Cahir. et al, reported that the cost associated with the PIP instances identified by condensed STOPP criteria in their study population was €318 per patient per year. The third study, Byrne et al., determined that the cost associated with PIP instances identified in their study population was €263 per patient per year.⁸

9.3.4. Unintended Consequences

9.3.4.1. Deprescribing: Negative Unintended Consequences

Deprescribing interventions do not always lead to an improvement in cognition scores.⁹ One potential unfavorable effect of deprescribing interventions is that, while the interventions have reduced medication costs, they do not always lead to a decrease in healthcare utilization, such as hospital admissions and primary care visits.¹⁰

9.3.4.2. Using the STOPP Criteria: Negative Unintended Consequences

With the exception of longer lengths of stay found in one study,⁶ no other unintended negative consequences were reported in the studies that examined the use of STOPP criteria to reduce ADEs. Although some researchers caution about risks related to cognitive declines when medications are reduced and/or eliminated, such findings were not discussed in the studies noted in this review.

9.3.4.3. Deprescribing: Positive Unintended Consequences

In addition to the clinical and process outcomes reported above, deprescribing also led to more positive quality of life in areas such as health transition, bodily pain, and general health.¹¹

9.3.4.4. Using the STOPP Criteria: Positive Unintended Consequences

No unintended positive consequences were reported in our review of the studies that examined the use of STOPP criteria to reduce ADEs.

References for Section 9.3

1.: Campins L, Serra-Prat M, Gozalo I, et al. Randomized controlled trial of an intervention to improve drug appropriateness in community-dwelling polymedicated elderly people. Fam Pract. 2017;34(1):36–42.10.1093/fampra/cmw073. [PubMed: 27605543] [CrossRef]
2.: Gibert P, Cabaret M, Moulis M, et al. Optimizing medication use in elderly people in primary care: Impact of STOPP criteria on inappropriate prescriptions. Arch Gerontol Geriatr. 2018;75:16–9.10.1016/j.archger.2017.10.022. [PubMed: 29169045] [CrossRef]
3.: Hannou S, Voirol P, Pannatier A, et al. Pharmacist intervention acceptance for the reduction of potentially inappropriate drug prescribing in acute psychiatry. Int J Clin Pharm. 2017;39(6):1228–36.10.1007/s11096-017-0513-8. [PubMed: 28905171] [CrossRef]
4.: Ilic D, Bukumiric Z, Jankovic S. Impact of educational intervention on prescribing inappropriate medication to elderly nursing homes residents. Srp Arh Celok Lek. 2015;143(3–4):174–9.10.2298/sarh1504174i. [PubMed: 26012127] [CrossRef]
5.: Unutmaz GD, Soysal P, Tuven B, et al. Costs of medication in older patients: before and after comprehensive geriatric assessment. Clin Interv Aging. 2018;13:607–13.10.2147/cia.S159966. [PMC free article: PMC5898882] [PubMed: 29674846] [CrossRef]
6.: O’Connor MN, O’Sullivan D, Gallagher PF, et al. Prevention of hospital-acquired adverse drug reactions in older people using screening tool of older persons’ prescriptions and screening tool to alert to right treatment criteria: A cluster randomized controlled trial. J Am Geriatr Soc. 2016;64(8):1558–66.10.1111/jgs.14312. [PubMed: 27365262] [CrossRef]
7.: Frankenthal D, Israeli A, Caraco Y, et al. Long-term outcomes of medication intervention using the screening tool of older persons potentially inappropriate prescriptions screening tool to alert doctors to right treatment criteria. J Am Geriatr Soc. 2017;65(2):e33–e8.10.1111/jgs.14570. [PubMed: 27943247] [CrossRef]
8.: Hill-Taylor B, Sketris I, Hayden J,et al. Application of the STOPP/START criteria: A systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact. J Clin Pharm Ther. 2013;38(5):360–72.10.1111/jcpt.12059. [PubMed: 23550814] [CrossRef]
9.: Office of Disease Prevention and Health Promotion. National Action Plan for Adverse Drug Event Prevention.Washington, DC: U.S. Department of Health and Human Services; 2014 https://health.gov/hcq/pdfs/ADE-Action-Plan-508c.pdf.
10.: Institute of Medicine Committee on Quality of Health Care in A. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington (DC): National Academies Press (US) Copyright 2001 by the National Academy of Sciences. All rights reserved.; 2001. [PubMed: 25057539]
11.: Ocampo CC, Garcia-Cardenas V, Martinez-Martinez F, et al. Implementation of medication review with follow-up in a Spanish community pharmacy and its achieved outcomes. Int J Clin Pharm. 2015;37(5):931–40.10.1007/s11096-015-0145-9. [PubMed: 26040837] [CrossRef]
12.: Kiel WJ, Phillips SW. Impact of pharmacist-conducted comprehensive medication reviews for older adult patients to reduce medication related problems. Pharmacy (Basel). 2017;6(1).10.3390/pharmacy6010002. [PMC free article: PMC5874541] [PubMed: 29301226] [CrossRef]
13.: Kimura T, Ogura F, Yamamoto K, et al. Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists’ assessment and intervention based on Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions criteria ver.2. J Clin Pharm Ther. 2017;42(2):209–14.10.1111/jcpt.12496. [PubMed: 28039932] [CrossRef]
14.: Price M, Davies I, Rusk R, et al. Applying STOPP guidelines in primary care through electronic medical record decision support: Randomized control trial highlighting the importance of data quality. JMIR Med Inform. 2017;5(2):e15.10.2196/medinform.6226. [PMC free article: PMC5491896] [PubMed: 28619704] [CrossRef]
15.: Cossette B, Ethier JF, Joly-Mischlich T, et al. Reduction in targeted potentially inappropriate medication use in elderly inpatients: a pragmatic randomized controlled trial. Eur J Clin Pharmacol. 2017;73(10):1237–45.10.1007/s00228-017-2293-4. [PubMed: 28717929] [CrossRef]
16.: De Bock L, Tommelein E, Baekelandt H, et al. The introduction of a full medication review process in a local hospital: Successes and barriers of a pilot project in the geriatric ward. Pharmacy (Basel). 2018;6(1).10.3390/pharmacy6010021. [PMC free article: PMC5874560] [PubMed: 29495567] [CrossRef]

9.4. Implementation

9.4.1. Summary of Evidence

We reviewed 27 studies, including 2 systematic reviews and 4 randomized controlled trials. Study interventions were heterogeneous, but most share common features. Interventions were delivered by pharmacists and/or physicians either in step-wise fashion (e.g., pharmacist conducts screening and makes recommendations; physicians review and accept/reject recommendations) or in collaboration (pharmacists and physicians review recommendations together). All studies were restricted to older adults (age 65 and older), but only three explicitly relied on geriatricians in the intervention. All STOPP interventions involved a screening step where STOPP criteria were used and included steps for making and accepting or rejecting recommendations generated from STOPP screening.

9.4.2. Barriers and Facilitators

This section describes barriers and facilitators to implementing interventions that focus on deprescribing or using STOPP criteria to reduce ADEs in older adults.

In the deprescribing literature, notable barriers to implementation included:

Pharmacists not adhering to study protocols.¹
Inadequate documentation of medication history.²^,³
Limited communication between pharmacists and physicians.¹^,⁴
Patients being discouraged from discontinuing medications by individual providers.⁵
Patients perceiving deprescribing as contradicting their provider’s recommendations.⁶
Scheduling conflicts, competing demands, and general lack of time, which impacted medication review meetings between pharmacists and physicians.⁴^,⁶^,⁷
Nonprescription medications (i.e., over-the-counter) that were not documented in medical databases, which prevented providers from seeing the full-range of medication use per patient and therefore not being able to accurately identify and include all patients who were at risk of polypharmacy in the study.¹
Lower acceptance rates of pharmacist interventions based on the STOPP criteria due to the lack of discontinuation of benzodiazepines.³^,⁸^,⁹

Key facilitators for deprescribing involved communication and collaboration between pharmacists and prescribing physicians during medication reviews,⁴^,⁶^,¹⁰ and educating pharmacists and physicians about the risks of polypharmacy and the use of unnecessary medications in older adult patients.¹¹

9.4.3. Resources To Assist With Implementation

The following resources were cited in our review of the evidence and can be used to implement future deprescribing practices:

Good Palliative Care Algorithm¹¹
-
A flow chart developed for use in nursing home settings to inform options for deprescribing.
Epocrates Online Drug-Drug Interaction Tool¹²
-
Free web-based drug interaction tool that assists in identifying combinations of medications that could be harmful. Visit https://online.epocrates.com/interaction-check for more information.
Canadian Deprescribing Network Patient and Pharmacist-Physician Materials¹
-
A compilation of materials to inform and educate patients and prescribing physicians about ways to reduce the use of inappropriate medications, including alternative treatment options and evidence-based pharmaceutical opinions. Visit https://www.deprescribingnetwork.ca/patient-handouts for patient materials and https://www.deprescribingnetwork.ca/pharmaceutical-opinions for physician information.

The following resources were cited in our review of the evidence related to using the STOPP criteria:

STOPP/START Toolkit Supporting Medication Review¹³
-
Designed to be used by healthcare professionals as a reference tool to support medication review for older adults. Developed by a consortium of professionals at the National Health Service North of England Commissioning Support Unit in the United Kingdom, the tool was validated for adults 65 years of age and older and can be downloaded at: https://www.herefordshireccg.nhs.uk/your-services/medicines-optimisation/prescribing-guidelines/deprescribing/748-stopp-start-herefordshire-october-2016/file.
Comprehensive Geriatric Assessment (CGA) Toolkit Plus¹⁴
-
A series of rules/suggestions related to high-yield problems in prescribing for older people in terms of both reducing medication burden (STOPP) and adding in potentially beneficial therapy (START). Visit https://www.cgakit.com/m-2-stopp-start for more information.

9.4.4. Gaps and Future Directions

9.4.4.1. Gaps

9.4.4.1.1. Deprescribing

There are notable gaps in the research of implementation efforts related to deprescribing. While many interventions have applied the use of specific criteria, algorithms, and protocols, only a few studies have considered other patient-related factors, including cost, patient preference, compliance and convenience, life expectancy, and other health outcomes associated with deprescribing. Furthermore, most interventions take place in either the acute care setting or ambulatory care setting. Finally, few interventions focus on the transition from acute care to ambulatory care and primary care settings.

9.4.4.1.2. STOPP Criteria

Research in STOPP is advancing rapidly, and increasing numbers of well-designed randomized or prospective studies are being published. Little if any progress has been made, however, in examining the impact of these interventions on short- and long-term clinical,¹⁵ utilization, and economic outcomes. Additionally, consensus is lacking on the most appropriate structure, format, and staffing, leading to heterogeneity of interventions.

9.4.4.2. Future Directions

9.4.4.2.1. Deprescribing

Recommendations for future deprescribing efforts include: factoring in perspectives and preferences of patients during the deprescribing process;⁷ developing protocols that target multiple rather than specific medications and/or diseases;⁷ and, with the expanding role of pharmacists, focusing on involving community pharmacists.¹⁶ More rigorous, long-term examination is necessary to further support the promise of this approach on reducing polypharmacy and ADEs.⁷^,¹⁷^,¹⁸

9.4.4.2.2. STOPP Criteria

Based on the emergent evidence, STOPP appears to be most effective in reducing PIMs in older adults when used in concert with other approaches. Recommendations for future investigations call for the integration of the STOPP criteria with clinical decision support procedures as part of electronic health records as a means to improve efficiency during the screening process.¹⁹ Combining STOPP—especially the 2014 revised version—with, or comparing it with, other screening tools such as the As Beers Criteria or the Medication Appropriateness Index could improve clinical appropriateness.²⁰ Researchers also recommend that future research examine the long-term clinical effects of using the STOPP criteria to reduce inappropriate medications and reduce ADEs.²¹

References for Section 9.4

1.: Martin P, Tamblyn R, Benedetti A, et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. J Am Med Assoc. 2018;320(18):1889–98.10.1001/jama.2018.16131. [PMC free article: PMC6248132] [PubMed: 30422193] [CrossRef]
2.: Hill-Taylor B, Sketris I, Hayden J, et al. Application of the STOPP/START criteria: A systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact. J Clin Pharm Ther. 2013;38(5):360–72.10.1111/jcpt.12059. [PubMed: 23550814] [CrossRef]
3.: Kiel WJ, Phillips SW. Impact of pharmacist-conducted comprehensive medication reviews for older adult patients to reduce medication related problems. Pharmacy (Basel). 2017;6(1).10.3390/pharmacy6010002. [PMC free article: PMC5874541] [PubMed: 29301226] [CrossRef]
4.: De Bock L, Tommelein E, Baekelandt H, et al. The introduction of a full medication review process in a local hospital: Successes and barriers of a pilot project in the geriatric ward. Pharmacy (Basel). 2018;6(1).10.3390/pharmacy6010021. [PMC free article: PMC5874560] [PubMed: 29495567] [CrossRef]
5.: Chan DC, Chen JH, Wen CJ, et al. Effectiveness of the medication safety review clinics for older adults prescribed multiple medications. J Formos Med Assoc. 2014;113(2):106–13.10.1016/j.jfma.2012.04.013. [PubMed: 24530244] [CrossRef]
6.: Ailabouni N, Mangin D, Nishtala PS. DEFEAT-polypharmacy: deprescribing anticholinergic and sedative medicines feasibility trial in residential aged care facilities. Int J Clin Pharm. 2019;41(1):167–78.10.1007/s11096-019-00784-9. [PubMed: 30659492] [CrossRef]
7.: Petersen AW, Shah AS, Simmons SF, et al. Shed-MEDS: pilot of a patient-centered deprescribing framework reduces medications in hospitalized older adults being transferred to inpatient postacute care. Ther Adv Drug Saf. 2018;9(9):523–33.10.1177/2042098618781524. [PMC free article: PMC6116773] [PubMed: 30181860] [CrossRef]
8.: Hannou S, Voirol P, Pannatier A, et al. Pharmacist intervention acceptance for the reduction of potentially inappropriate drug prescribing in acute psychiatry. Int J Clin Pharm. 2017;39(6):1228–36.10.1007/s11096-017-0513-8. [PubMed: 28905171] [CrossRef]
9.: Sennesael AL, Dalleur O, Henrard S, et al. Implementing a screening tool to improve prescribing in hospitalized older patients: a pilot study. Int J Clin Pharm. 2018;40(1):15–9.10.1007/s11096-017-0563-y. [PubMed: 29170978] [CrossRef]
10.: Kojima G, Bell C, Tamura B, et al. Reducing cost by reducing polypharmacy: the polypharmacy outcomes project. J Am Med Dir Assoc. 2012;13(9):818.e11–5.10.1016/j.jamda.2012.07.019. [PMC free article: PMC3489959] [PubMed: 22959733] [CrossRef]
11.: Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy. Arch Intern Med. 2010;170(18):1648–54.10.1001/archinternmed.2010.355. [PubMed: 20937924] [CrossRef]
12.: Tamura BK, Bell CL, Lubimir K, et al. Physician intervention for medication reduction in a nursing home: the polypharmacy outcomes project. J Am Med Dir Assoc. 2011;12(5):326–30.10.1016/j.jamda.2010.08.013. [PMC free article: PMC3102122] [PubMed: 21450207] [CrossRef]
13.: National Health Service Cumbria. STOPP START Tool to support medication review. https://www.herefordshireccg.nhs.uk/your-services/medicines-optimisation/prescribing-guidelines/deprescribing/748-stopp-start-herefordshire-october-2016/file. Accessed November 7, 2019.
14.: O’Mahony D. Resources for the Comprehensive Geriatric Assessment based Proactive and Personalised Primary Care of the Elderly. https://www.cgakit.com/m-2-stopp-start. Accessed November 7, 2019.
15.: Cossette B, Ethier JF, Joly-Mischlich T, et al. Reduction in targeted potentially inappropriate medication use in elderly inpatients: a pragmatic randomized controlled trial. Eur J Clin Pharmacol. 2017;73(10):1237–45.10.1007/s00228-017-2293-4. [PubMed: 28717929] [CrossRef]
16.: Tannenbaum C, Martin P, Tamblyn R, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med. 2014;174(6):890–8.10.1001/jamainternmed.2014.949. [PubMed: 24733354] [CrossRef]
17.: Ocampo CC, Garcia-Cardenas V, Martinez-Martinez F, et al. Implementation of medication review with follow-up in a Spanish community pharmacy and its achieved outcomes. Int J Clin Pharm. 2015;37(5):931–40.10.1007/s11096-015-0145-9. [PubMed: 26040837] [CrossRef]
18.: McKean M, Pillans P, Scott IA. A medication review and deprescribing method for hospitalised older patients receiving multiple medications. Intern Med J. 2016;46(1):35–42.10.1111/imj.12906. [PubMed: 26387783] [CrossRef]
19.: Price M, Davies I, Rusk R, et al. Applying STOPP guidelines in primary care through electronic medical record decision support: Randomized control trial highlighting the importance of data quality. JMIR Med Inform. 2017;5(2):e15.10.2196/medinform.6226. [PMC free article: PMC5491896] [PubMed: 28619704] [CrossRef]
20.: Kimura T, Ogura F, Yamamoto K, et al. Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists’ assessment and intervention based on Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions criteria ver.2. J Clin Pharm Ther. 2017;42(2):209–14.10.1111/jcpt.12496. [PubMed: 28039932] [CrossRef]
21.: Unutmaz GD, Soysal P, Tuven B, et al. Costs of medication in older patients: Before and after comprehensive geriatric assessment. Clin Interv Aging. 2018;13:607–13.10.2147/cia.S159966. [PMC free article: PMC5898882] [PubMed: 29674846] [CrossRef]

Conclusion and Comment

Being able to prevent unnecessary ADEs that are associated with the use of inappropriate medication use or polypharmacy is especially important for older adults who are affected by multiple ailments and who inevitably traverse multiple healthcare settings and providers for treatment. As the evidence reviewed in this chapter suggests, deprescribing to reduce polypharmacy and use of the STOPP criteria to reduce PIMS are two approaches to consider. Albeit still emerging, studies on deprescribing highlight its potential in helping providers adjust down and/or eliminate medications based on the condition/need of patients. However, more research is needed to assess deprescribing in relation to patient adherence, compliance, and preference, as patients play a key role in a provider’s ability to effectively monitor and adjust medication and treatment plans.

With regard to using the STOPP criteria to reduce PIMS, evidence suggests it is the most effective approach, but also note that it often does not—and should not—stand alone. In order to ensure that older adults are given the best possible care, in addition to screening their prescriptions for PIMS (i.e., using STOPP), it is equally important to identify more appropriate treatment options, thus also including the START criteria. More appropriate medication selection is also achieved through the use of the Beers Criteria or the Medical Appropriateness Index (MAI), which are other interventions that often accompany the use of STOPP.

While the literature in this review expands the existing knowledge of practices to reduce harm and preventable ADEs for elderly patients, in particular, the field will undoubtedly benefit from more studies that examine the short- and long-term clinical effects of reducing polypharmacy and PIMS through deprescribing and using the STOPP criteria.

: Reviewer: Giulia Norton, Ph.D., M.P.H., and Scott Winiecki, M.D.

Bookshelf ID: NBK555524

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