From 2006 to 2016, the number of Americans 65 years and older increased from 37.2 million to 49.2 million (33% increase) and is projected to reach 98 million by 2060.1 An estimated 98% of people 65 years and older deal with 2 or more chronic diseases and take at least 5 prescription medications to treat or manage these conditions.2 However, for older adults in particular, there are also associated risks. For instance, polypharmacy—taking multiple medications concurrently—and the use of potentially inappropriate medications (PIMs) can lead to adverse drug events (ADEs).3,4 Broadly defined as an injury experienced by a patient that results from exposure to a medication (e.g., medication errors, adverse drug reactions, allergic reactions, or overdoses), ADEs have been associated with thousands of visits to the emergency department (ED), hospitalizations, and mortality.5 However, up to half of identified ADEs are preventable,6 and across all health care settings, they are one of the most common types of preventable adverse events.7
A range of interventions and approaches have been developed and studied to address preventable ADEs. This review focuses on 2 approaches in particular: (1) deprescribing to reduce polypharmacy and (2) the use of the Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP) criteria to reduce PIMs. Deprescribing involves reducing doses or stopping medications that are not useful or no longer needed to reduce polypharmacy, reduce harm, and improve health.8 STOPP is a validated, evidence-based list of 80 criteria that are used to assess for potentially inappropriate prescribing (PIP) in older adults.9
For this review, we examined the question: What is the effect of interventions for deprescribing and using the STOPP criteria on preventable ADEs for older adults? It is important to note that deprescribing and the STOPP criteria are not themselves interventions: deprescribing is an approach, and the STOPP criteria are used in a screening tool that was part of the interventions reviewed.
First published in 2008 and revised in 2014, STOPP is often complimented with a companion tool, the Screening Tool to Alert to Right Treatment (START), to help facilitate medication reviews for multimorbid older adults. START is typically used in addition to STOPP, whereas STOPP is used both in tandem with START and as a standalone tool. In this review, the focus is on the STOPP criteria and START is referenced, as appropriate.10
Literature Search Strategy
We searched 2 databases (CINAHL and MEDLINE) for peer-reviewed literature published from 2008 to 2018 using terms related to deprescribing and STOPP interventions, targeted at older adults and aimed at outcomes of interest (e.g., reduction of preventable ADEs, polypharmacy, or PIMs, and other relevant outcomes). See Supplemental Material for the search terms, http://links.lww.com/JPS/A334.
The initial search yielded 988 records across the 2 databases and an additional 9 studies identified from reference lists. After removing duplicates, 722 titles and abstracts were screened from which 194 studies were reviewed for full text (see the Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram in Fig. 1).
Studies were included if they were published in English, explicitly focused on deprescribing, polypharmacy, use of STOPP, and/or related interventions, targeted at older adults, and examined the effectiveness of these interventions on PIMs and preventable ADEs. Articles were excluded if (1) the study was out of scope, (2) the focus was on children or pediatric care, (3) not an intervention study (e.g., epidemiological studies, and commentaries), or (4) outcomes were not reported.
As shown in Table 1, 27 articles consisting of 26 studies and 1 systematic review met the inclusion criteria and evaluated interventions related to deprescribing (n = 14 studies: Table 2) or use of the STOPP criteria to reduce PIMs (n = 12 studies, 1 systematic review; Tables 2, 3) in older adults.
Within the deprescribing literature, 5 of the studies were randomized controlled trials (RCTs), 4 were feasibility studies, 2 were intervention studies, 1 was a cost study, 1 was a pilot study, and 1 was a hybrid implementation-effectiveness design. Most of the studies sample sizes were small, ranging from 40 to 490 participants. Studies evaluated a range of interventions, from protocols and clinical decision support tools to patient education and medication reviews. Most of the deprescribing interventions were delivered by pharmacists in a consultative role or in collaboration with providers, or conducted by providers themselves. Although the focus of this review was on older adults, only 3 interventions involved geriatricians. Most of the deprescribing interventions were in long-term care facilities, community pharmacies, inpatient hospital geriatric units, hospital outpatient departments, and hospitals during discharge. The studies varied widely in the outcomes examined, with the majority evaluating the effect of the interventions on process outcomes. Findings from the studies are presented by clinical, process, and economic outcomes, and then by type of intervention within each of these categories of outcomes.
Only 2 studies evaluated the effect of deprescribing interventions on clinical outcomes, and the outcomes varied with the specific interventions. Ocampo et al12 found that a pharmacist-led medication review with an 18-month follow-up period in community pharmacies identified 408 negative uncontrolled health problems 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, whereas the number of patients who were not adherent decreased from 68 to 1 (P < 0.0001). 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.11 These researchers also examined collaborative medication reviews with general practitioners of patients 65 years and older in a residential care facility. Their study also noted a significant reduction in drug burden index scores by 0.34 (P < 0.001), reflecting a decrease in the cumulative exposure to the 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). In addition, the number of adverse drug reactions decreased by 4.24 (P < 0.05) after 6 months.11 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.20 Wouters et al23 sought to improve prescribing in nursing home residents by implementing the Multidisciplinary Multistep Medication Review. The randomized control trial took place on nursing home wards and consisted of an evaluation of the patient’s perspective, health history, and use of medications; a meeting between the physician and pharmacist; and the execution of medication changes. 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.
Many deprescribing studies focused on process-related outcomes such as number of medications prescribed or polypharmacy, which is expected to lead to clinical improvements or a reduction in ADEs. Findings from these studies are presented by the types of interventions.
Protocols, Algorithms, and Clinical Decision Support Systems
Among the 3 studies focusing on the use of protocols, algorithms, and clinical decision support systems to promote deprescribing, 2 studies found significant decreases in the number of medications prescribed. Petersen et al19 found that a patient-centered deprescribing protocol called Shed-MEDS, implemented in 4 phases: (1) medication history and list confirmed, (2) evaluate medication for deprescribing, (3) decide with the patient, and (4) synthesize and communicate recommendations among Medicare beneficiaries prescribed 5 or more medications, significantly reduced the mean number of prescribed medications from 11.6 to 9.1 (P = 0.032) for those with whom the protocol was used. Garfinkel and Mangin14 worked with elderly patients in Israel to implement the Good Palliative-Geriatric Practice algorithm, an evidence-based flowchart for medication discontinuation, which recommended discontinuing a total of 311 medications for 64 patients. McKean et al17 worked with patients 65 or older taking 8 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 5-step clinical decision support (CDS) tool to determine medications eligible for discontinuation. The intervention led to a 34.3% decrease in non-PRN medications, a small but non-significant decrease in PRN (as needed) medications and a significant decrease in the number of medications per patient at discharge compared with at admission (median change, 7 versus 10 medications; P < 0.001).
Pharmacist-Led Medication Review Interventions
Two pharmacist-led medication review interventions across a number of settings involved deprescribing. Lenander et al.16 found that a pharmacist-led medication review in a primary care setting targeting patients 65 years and older with 5 or more different medications led to a decrease in drug-related problems. Using American Geriatric Society’s 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 medications prescribed in the intervention group (P < 0.046). Veggeland and Dyb24 observed the effect of adding a clinical pharmacist performing medication reviews to a geriatric care hospital team. They found that it led to changes including discontinuation of medications, dose reduction, or decision to adjust medications at a later stage of hospitalization.
Clinician-Led Medication Reviews
We found one study of a clinician-led medication review. Tamura et al21 worked with geriatric medicine fellows in a long-term care facility to implement a medication review using the updated Beers Criteria for patients (average age, 83 years) with 9 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), which were statistically significant but may be not be clinically significant.
Pharmacist and Clinician Medication Reviews
Two studies combined pharmacist and clinician medication review. Chan and colleagues13 examined the effectiveness of a medications safety review clinic for geriatric outpatients 65 years or older who were prescribed 8 or more chronic medications or who had visited at least 3 different physicians at the 2 participating hospitals within 3 months. Four medication review sessions were performed by 2 research assistants, 1 clinical pharmacist, and 1 geriatrician, leading to a mean decrease in chronic medications from 9.0 to 8.6 (P < 0.05). In addition to what was previously discussed, the RCT of the Multidisciplinary Multistep Medication Review intervention by Wouters and colleagues23 found that successful discontinuation without relapse or severe withdrawal symptoms of at least one inappropriate medication was greater for nursing home residents in the intervention group compared with those who were not exposed to the intervention (i.e., the control group; 39.1% versus 29.5%; 95% confidence interval [CI], 1.02–1.75).
Patient Educational Interventions
Educational interventions for patients have also been used to reduce polypharmacy. Tannenbaum et al22 found that a direct-to-consumer educational intervention using an 8-page booklet to describe the risks of benzodiazepine use and a stepwise tapering protocol led to a 27% discontinuation of benzodiazepines among community pharmacy patients 65 years or older in the intervention group compared with 5% in the control group (95% CI, 14%–32%) at 6 months after the intervention. Martin et al18 studied a consumer-based educational intervention led by pharmacists in community pharmacies providing an educational brochure to patients 65 years and older. The study resulted in 43% of the intervention group no longer filling inappropriate medications compared with 12% of the control group (95% CI, 23%–38%).
One study assessed the economic impact of a deprescribing intervention. Kojima et al15 evaluated the effect on medication costs of a physician intervention using 2 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).
All of the 12 studies in this review used the STOPP criteria in screening followed by steps for making, accepting, or rejecting recommendations generated. One article was a systematic review with meta-analysis and narrative summary. Among the individual studies, 5 of the studies were RCTs, 2 were intervention studies, 1 was a retrospective cohort study, 1 was a retrospective before and after design, 1 was a prospective cohort study, and 2 were observational studies. Most of the studies sample sizes were small, ranging from 52 to 1579 participants. In the studies, most of the interventions integrated STOPP criteria into medication reviews as part of a usual checkups and geriatric assessments. The STOPP interventions were delivered by pharmacists or providers during medication reviews. All 13 studies focused on patients 65 years and older, whereas one of those studies restricted inclusion to patients 75 years and older. The study settings included inpatient, long-term care settings, and primary care. The 12 single studies that evaluated the STOPP criteria examined clinical, process, and economic outcomes.
One single study and the systematic review examined clinical outcomes. In the systematic review, Hill-Taylor et al25 found that one study showed an association between a STOPP/START intervention and improvement in medication appropriateness, as measured by the Medication Appropriateness Index (absolute risk reduction of 35.7%) and the Assessment of Underutilization index (absolute risk reduction of 21.2%). No significant findings were noted in the relationship between STOPP/START interventions and reduction of falls or all-cause mortality. No studies within the systematic review measured quality of life outcomes.
Cossette et al26 looked at readmissions and inpatient death rates but found no significant decrease between the intervention and control groups.
Seven studies examined the use of the STOPP criteria on prescribing practices. Campins et al27 reported that the STOPP tool used by pharmacists found that 27% of the intervention population’s (n = 252) prescriptions were potentially inappropriate. Most of these prescriptions were then changed as follows: 43% were discontinued, 33% received a dose adjustment, 14% were substituted for more appropriate medications, and 10% received a new prescription. Similarly, Gibert et al28 used STOPP in primary care consultations in France, resulting in a 38% reduction in the number of PIMs (n = 170 versus 106) across about 45% of patients (n = 44; P < 0.001). Also, De Bock et al29 used STOPP as part of a medication review and found that 20% of recommendations were accepted. Kiel and Phillips30 used the STOPP/START criteria in a pharmacist-led medication review with an acceptance rate of 35%.
Cossette et al26 used STOPP to develop a computer alert system as part of a pharmacist-physician intervention to reduce PIMs. The intervention group saw a significant drug cessation and dosage decrease at 48 hours after alert (30%) and hospital discharge (20.8%) compared with the control group.
Hannou et al31 introduced a part-time ward-based clinical pharmacist to a psychiatric unit’s multidisciplinary team and screened prescriptions for potentially inappropriate drug prescribing using the STOPP/START criteria. The intervention was measured by the acceptance rate of pharmacist interventions. The global pharmacist intervention acceptance rate was 68%, and that based on STOPP/START was 47%. When 2 STOPP criteria (the prescribing of benzodiazepines and the prescribing of neuroleptic drugs to patients who had fallen in the last 3 months) were removed from the analysis, the acceptance rate for STOPP/START-based pharmacist interventions increased to 67%.
In the study by Ilic et al,32 an educational intervention targeting both physicians and nursing home residents provided information on the START/STOPP and Beers Criteria, as well as adherence, adverse drug reactions, and drug-drug interactions. According to the STOPP criteria, 70 medications were inappropriately prescribed before the intervention and 20 medications after 6 months. The median number of inappropriately prescribed medications 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).33
Studies of using STOPP criteria examined economic outcomes. After implementing a comprehensive geriatric assessment (CGA) that included the STOPP criteria, the findings reported by Unutmaz et al34 suggested that by using the tool to assess PIMs, medication costs were reduced by approximately $13 a month, per patient. In addition to the economic savings of not having patients pay for medications that they did not need, the tool was associated with savings of $5.68 per month per patient to improve errors of omission like potentially prescribing omissions (PPOs) where medications that may be more appropriate are not prescribed. O’Connor et al35 also 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). Frankenthal et al36 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 in the control group (P < 0.001) at the 24-month follow-up. Hill-Taylor et al25 reviewed 3 studies on the direct costs of PIPs and PPOs that found the cost associated with PIP and PPO ranged from €188 to €318 per patient per year.
This review contributes to the evidence of effectiveness on interventions using deprescribing and STOPP screening criteria to address preventable ADEs in older adults. The deprescribing interventions included in this review used protocols, algorithms, CDS tools, educational interventions, and most commonly medication reviews conducted either by pharmacists, providers, or a combination thereof. Deprescribing interventions, commonly part of medication reviews if not within protocols or decision tools, were often found to significantly reduce polypharmacy in the studies we reviewed. Medication reviews involving both pharmacists and clinicians effectively decreased medication use in 2 studies. The STOPP screening criteria were used within interventions to identify PIMs and make recommendations or changes accordingly. Many of the interventions using the STOPP criteria—regardless of who or how the criteria were used—decreased PIMs, often significantly. Although studies in this review observed some statistically significant differences in polypharmacy or PIMs, given these are process or intermediate outcomes, it is unclear whether these differences were always going to be clinically significant. In addition, the heterogeneity of the often multicomponent interventions in which deprescribing or STOPP criteria were used as well as the range of health care settings and professionals conducting the interventions limited the extent to which findings could be synthesized across studies. The strength of evidence was further limited by the study designs and often small sample sizes, especially within deprescribing interventions, whereas the STOPP criteria interventions included a few studies with observations in larger samples sizes.
This review also points to several gaps and future directions for research and interventions to advance the field. Recommendations for future deprescribing interventions and studies could factor in perspectives and preferences of patients during the deprescribing process11; develop protocols that target multiple rather than specific medications and/or diseases11; and, with the expanding role of pharmacists, focus further on the involvement of community pharmacists,14 especially with pharmacists expanding scopes of practice and the ability to establish collaborative practice agreements between pharmacists and providers. More rigorous, long-term studies with larger sample sizes are needed to further understand deprescribing interventions long-term effects in reducing polypharmacy and preventable ADEs.12,17,19 Studies would also be improved if they examined clinical outcomes, not just process or intermediate outcomes. Comparative effectiveness study of different deprescribing interventions, whether single or multicomponent would also be beneficial to the field.
Recommendations for future research related to the STOPP criteria include embedding it within CDS tools in electronic health records, as a means to improve efficiency during the screening process.37 Combining use of the STOPP criteria with, or comparing it with, other screening tools such as the Beers Criteria or the Medication Appropriateness Index could improve clinical appropriateness.38 Unutmaz et al34 have recommended that future research examine the long-term clinical effects of using the STOPP criteria to reduce inappropriate medications and reduce ADEs.
Regardless of the type of intervention, an essential component to ensure that any evidence-based approaches or criteria effectively change prescribing practices and that key outcomes can be the implementation approaches or strategies that are used.39,40 Although this review included one study that was an implementation-effectiveness design study, there is vast opportunity to expand the field’s understanding of how to effectively implement these interventions.41 Further systematic reviews and meta-analyses, where feasible, for other patient safety practices addressing preventable ADEs in older adults would also be valuable to the field.
This review offers additional insights into the effectiveness of deprescribing interventions and interventions involving the STOPP criteria on key process outcomes, as well as some clinical and economic outcomes. It also points to opportunities for future research to understand effective interventions to reduce the harms of preventable ADEs in older adults.
This work was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services (contract numbers HHSP233201500013I and HHSP23337002T).
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