Table 1. Summary of Included Systematic Reviews Aimed at Addressing Polypharmacy.
| Source | Literature search coverage | No. of articles included and study designs | Population | Setting | Intervention type | Primary outcome measure | Major conclusion |
|---|---|---|---|---|---|---|---|
| Johansson et al,29 2016 | Database inception-July 2015 | 25 Studies (21 RCTs, 4 non-RCTs) | Adults aged ≥65 y (or 80% of study population aged ≥65 y) receiving ≥4 medications | Community settings/primary care (15), care/nursing homes or assisted living facilities (7), hospital (3) | Pharmacist-led medication review or multicomponent intervention (13), physician-led intervention (4), multidisciplinary team-led intervention (8) | Mortality, hospitalization, changes in No. of medications | The intervention strategies evaluated did not present compelling evidence on reducing mortality, hospitalization rates, or medication use. The interventions in the studies are complex and it is difficult to assess which intervention should be implemented to reduce inappropriate polypharmacy. |
| Page et al,30 2016 | Database inception-February 2015 | 116 Studies (56 RCTs, 22 comparative studies with concurrent control, and 37 comparative studies without concurrent control) (1 article reported on 2 studies) | Older adults (age ≥65 y) receiving ≥1 medication | Community settings (73), residential aged care facilities (29), hospital (14), hospital/community (1), community/residential care (1) | Deprescribing of ≥1 medication, medication class, or therapeutic category; deprescribing polypharmacy; medication reviews; educational programs for health care professionals | Mortality | A notable reduction in mortality was observed in nonrandomized studies and those focusing on patient-specific interventions; however, there was no statistically significant decrease in mortality in randomized studies and studies centered on generalized education programs. |
| Thillainadesan et al,18 2018 | January 1996- April 2017 | 9 RCTs | Older populations with a median age of ≥65 y | Hospital (9) | Deprescribing interventions were either pharmacist- (n = 4), physician- (n = 4), or multidisciplinary team- (n = 1) led | Reduction in PIMs | Based on the available evidence, it appears that deprescribing interventions within a hospital setting are viable and, in most cases, may reduce PIMs while also maintaining safety. |
| Rankin et al,13 2018 | Database inception-February 2018 (18 studies before 2013 were from a prior review) | 18 RCTs, 10 cluster RCTs, 2 non-RCT studies, 2 controlled pre-post studies | Older adults (age ≥65 y, or 80% of study population aged ≥65 y) who had >1 long-term medical condition and were receiving polypharmacy (receiving ≥4 regularly prescribed medications) | Hospital (16), primary care (10), nursing homes (6) | Complex, multifaceted interventions (31), physician-led deprescribing (4), educational interventions to prescribers (10) | Medication appropriateness, PIMs, PPOs, hospital admissions | The outcomes of interventions aimed at enhancing appropriate polypharmacy, such as medication reviews, on clinically significant improvement remain uncertain. Nevertheless, these interventions may offer some slight benefits in terms of reducing PPOs. This conclusion is drawn from just 2 studies, both of which had substantial limitations concerning bias risk. |
| Mizokami et al,19 2019 | January 1972-March 2017 | 9 RCTs | Older adults receiving ≥5 medications | Hospital inpatients (3), community outpatients (6) | CMR of 3 levels: type I (prescription review), type II (medication adherence review), type III (focus on face-to face review of medicines and condition with the patient) | Total number of unplanned hospitalizations or rehospitalizations, and the number of patients experiencing (single or multiple) hospitalizations or rehospitalizations between CMR types | Type III CMRs led to a significant decrease in unplanned admissions among elderly patients during their hospitalization, but had no association with hospital admission rates for outpatient older adults. |
| Ali et al,20 2020 | Database inception-April 2019 | 7 RCTs, 2 observational studies | Older adults aged ≥65 y with chronic conditions who were receiving ≥5 medications/d | Community settings (6), residential care facilities (2), geriatric outpatient clinics (1) | Medication reviews (4), geriatric assessments/ medication screening (2) deprescribing interventions (3) | Falls, physical function | The evidence indicates that interventions addressing polypharmacy have favorable and clinically significant impacts on mobility outcomes, as evidenced by a decrease in the incidence of falls. |
| Lum et al,21 2020 | Database inception-May 2019 | 5 RCTs, 1 retrospective quasi-experimental study | Adults patients (age ≥18 y) with multiple prescription medications and having ≥1 of 3 cardiometabolic diseases: stroke, heart disease, and type 2 diabetes | Cardiac rehabilitation clinic (1), community setting (5) | Pharmacist-led multicomponent intervention (5), clinical-decision support tool–based intervention (1) | Quality of life, drug-related problems, surrogate markers, health care use, and costs | The outcomes of polypharmacy interventions for individuals with cardiometabolic diseases are inconsistent. Interventions involving more frequent and longer direct patient care sessions might yield the most favorable outcomes. |
| Hasan Ibrahim et al,22 2021 | Database inception-April 2020 | 6 RCTs, 1 CBA | Older adults (age ≥65 y) with both multimorbidity (presence of ≥2 long-term conditions) and polypharmacy (concomitant use of ≥4 medications) | Primary care (7) | Practice-based pharmacist-led interventions in primary care (7) | Drug-related problems, medication appropriateness, medication adherence, No. of medications, quality of life, hospital admissions/ readmissions | This systematic review revealed a scarcity of evidence, with only 7 studies exploring the services provided by pharmacists in optimizing medication management for older individuals dealing with both multimorbidity and polypharmacy. |
| Laberge et al,23 2021 | 2004-2020 | 6 cluster RCTs, 3 RCTs, 1 pre-post, 1 cohort with control | Populations at least 80% older adults (age ≥65 y) with multimorbidity (defined as having ≥2 chronic conditions) and having polypharmacy | Primary care clinics (n = 4), nursing homes (n = 1) pharmacies (n = 3), hospital (1), academic medical center (1) | CMRs (10), pharmacogenetic testing with a clinical decision-support tool (1) | PIM use, ADEs, No. of medications, hospital admissions/ readmissions, costs of interventions, cost per PIM avoided, No. of PIMs avoided, No. of ADEs avoided | Because of the diversity in reported outcomes and the suboptimal quality of the economic assessments, the authors acknowledged their inability to reach a definite conclusion regarding the cost-effectiveness of interventions aimed at optimizing medication use. |
| Lee et al,24 2021 | Database inception-August 2020 | 3 RCTs, 2 cluster RCTs | Older adults (age ≥65 y) | Community setting (4), long-term care (1) | Pharmacist-led FRID deprescribing appropriateness (3), physician-led FRID deprescribing appropriateness (2) | Rate of falls, incidence of falls, rate of fall-related injuries | Insufficient strong and high-quality evidence is available to either support or contradict the association between a deprescribing strategy for fall-related injuries in older adults solely based on FRID |
| Tasai et al,25 2021 | Database inception-January 2018 | 4 RCTs (1 study not included in the quantitative analysis due to lack of data) | Older adults (age ≥65 y) receiving ≥4 prescribed medications | Community settings (4) | CMR (4) | Quality of life, hospitalizations, ED visits, medication adherence | Evidence illustrates that comprehensive clinical medication reviews conducted by community pharmacists for older individuals with multiple medications may help in reducing the risk of ED visits. |
| O’Shea et al,262022 | Not reported | 3 RCTs; 6 noncomparative studies, 3 observational studies | Adults with multimorbidity and polypharmacy | Community settings (10), long-term care (2), | Pharmacist-led CMR with pharmacogenetics testing (8), physician-led pharmacogenetics testing (3), pharmacogenetics review (1) | Hospitalizations, ED visits, outpatient visits, health care costs, costs of genetic testing | Owing to the absence of methodologically strong, high-quality research, limited sample sizes, and relatively brief follow-up periods, the authors encountered limited evidence regarding pharmacogenetic interventions in enhancing outcomes for patients with both multimorbidity and prescribed polypharmacy. |
| Reeve et al,27 2022 | 2009-June 2020 | 7 RCTs, 2 non-RCTs, 4 pre-post studies, 2 prospective cohort, 2 retrospective cohort, 2 cross-sectional, 1 exploratory study | Older adults (age ≥50 y) with ≥2 long-term medical conditions and polypharmacy (≥5 long-term medications/d) | Primary care (10), secondary care (7), tertiary care (2), pharmacy call center (1) | Physician-led deprescribing (11), pharmacist-led deprescribing (5), multi-disciplinary team deprescribing (4) | Associations (eg, prescribing-related outcomes), associations (eg, hospitalizations, falls, quality of life), safety (eg, adverse events), acceptability (eg, satisfaction) | The collective reviews acknowledge that deprescribing is a multifaceted intervention and offer endorsement for the safety of well-structured deprescribing approaches. However, the authors also emphasize the necessity of incorporating patient-centered and contextual elements into the best practice models. The authors concluded that the studies provided clear accounts of the objectives of the deprescribing interventions and the target patient populations. Nevertheless, they frequently lacked comprehensive information concerning the individuals responsible for delivering the intervention and the specific methods used. |
| Stötzner et al,28 2022 | Database inception-July 2021 | 15 RCTs, 27 non-comparison pre-post studies, 5 randomized pre-post approach, 9 retrospective studies, 2 study designs not reported | Patients with all psychiatric diagnoses | Nursing homes (39), psychiatric inpatient settings (10), psychiatric outpatient settings (9) | Individual medication review (22); CMR (36); educational programs, guideline reviews, or consulting services (12); automatic alerts (4) | Drug-related problems, medication appropriateness, hospital admissions, ED visits, falls, frailty measures, mortality, cognitive status, health care costs | Interventions targeting polypharmacy can result in enhanced drug-related outcomes among psychiatric populations. Nevertheless, changes in clinical outcomes were frequently minimal and typically less reported. |
Abbreviations: ADE, adverse drug event; CBA, cost-benefit analysis; CMR, comprehensive medication review; ED, emergency department; FRID, fall risk–increasing drugs; PIM, potentially inappropriate medication; PPO, potential prescribing omission; RCT, randomized clinical trial.