As shown in Figure 1, 44 of the 278 full-text articles reviewed for eligibility met inclusion criteria.15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67 Six were rated high risk of bias and are not included in the analyses.62,63,64,65,66,67 Of the remaining 38, 12 were randomized controlled trials and 26 were cluster randomized controlled trials. Included studies were similar with respect to study population (older adults taking multiple medications and living in the community) and setting (outpatient primary care clinics). Most interventions focused on general deprescribing, although some studies targeted medication classes (e.g., psychotherapeutic) or specific goals (e.g., falls reduction). We report results by the type of intervention studied: CMR (k = 22), educational interventions (k = 12), or computerized decision support (k = 4). For more detailed information on the included studies, see Appendix B.
Comprehensive Medication Review
Twenty-two trials evaluated the effect of comprehensive medication review (CMR) compared with a control group, most often usual care.15,16,17,19,20,25,27,28,29,31,32,33,34,35,36,37,38,39,41,42,43,44,45,54,58,59,60,61 Generally the CMR interventions were conducted by a pharmacist (k = 16) and included a chart review, in-person patient interview, and provider consultation, culminating in recommendations for medication regimen changes. Eight studies also included a follow-up intervention with patients to reinforce the recommendations, such as 1 to 3 home care visits by nurses or telephone calls by pharmacists over the 2- to 12-month follow-up period. Five trials were conducted in the USA, one in Canada, one in Malaysia, and 15 in Europe. We judged the risk of bias to be low in 5 trials and medium in 17. Studies enrolled 9482 patients, with study sample sizes ranging from 25 to 1403. Certainty of evidence for primary outcomes is summarized in Table 1.
All-cause mortality was reported in 12 trials enrolling 4875 patients with follow-up ranging from 1 to 12 months.15,16,17,19,20,27,28,29,36,37,38,39,44,45,59,61 Compared with usual care, CMR resulted in a 26% relative risk reduction (OR 0.74, 95% CI: 0.58 to 0.95, I2 = 0) corresponding to a 1.4 percentage point absolute reduction (95% CI: − 2.7 to − 0.1) in all-cause mortality (Fig. 2). Overall, CMR may result in a small reduction in all-cause mortality (low certainty).
Hospitalizations over a wide range of follow-up durations were reported in 12 studies with a combined enrollment of 5672 participants.19,20,27,28,29,31,32,33,35,36,39,43,44,58,59,61 None of these studies reported a difference between the intervention and control groups with respect to the number of participants with one or more hospitalizations during follow-up. In the 6 RCTs that could be pooled,19,20,39,44,58,59,61 20.4% of people in the deprescribing group were hospitalized vs 19.8% in usual care for an absolute risk difference of 0.6% (95% CI: − 2.3 to 3.5) over follow-up durations ranging from 3 to 24 months (Fig. 3). Overall CMR probably results in little to no reduction in hospitalizations (moderate certainty).
Health-Related Quality of Life
Health-related quality of life was reported in 11 studies measured with either the EuroQual Quality of Life scale (EQ-5D or EQ-5D VAS) (k = 5), the Short Form Health Survey (SF-12/36 or physical, mental subscales) (k = 5), or both (k = 1).16,17,19,20,28,29,31,32,33,34,35,39,42,43,45,59 Nine studies reported no difference between the intervention and control groups in health-related quality of life at study end. Overall, CMR may result in little to no improvement in health-related quality of life scores (low certainty).
Four trials reported fall outcomes,16,17,41,59,60 only one of which found a difference between the intervention and control groups. This study (medium risk of bias) enrolled 620 adults ≥ 70 years old and focused on medications that might increase risk of falls. The intervention group had a 62% decrease in fall-related diagnoses during the 1-year study (OR 0.38, P < .01, CI not reported) despite no difference between groups in the total number of medications or number of psychoactive medications at follow-up.60
The IMPROveFALL trial (medium risk of bias) enrolled 612 older adults who had visited an emergency room because of a fall; there was no difference between the intervention and control groups at 12 months in the number of falls (37% vs 34%; absolute risk difference 4%, 95% CI: − 4 to 12).16,17 The other 2 trials did not designate falls as a primary outcome, had small sample sizes (N = 259 and 157), and had short lengths of follow-up (less than 3 months).41,59 Overall, CMR may result in little to no reduction in falls (low certainty).
Reduction in Potentially Inappropriate Medications
Nine of thirteen trials that reported a potentially inappropriate medication outcome found fewer PIMs in the intervention group than in the control group; the difference was statistically significant in 7 studies (Table 3).16,17,25,28,29,34,41,42,54 The variability in outcome definitions precluded pooling of results. However, we calculated standardized mean differences for the five trials that reported the Medication Appropriateness Index.15,28,29,34,42,43 In these trials, the intervention effect, as measured by Cohen’s d, was less than small in two,15,43 small in one,34 and moderate in two28,29,42 (see Appendix C).
We identified 12 trials18,21,22,23,24,30,40,46,47,50,51,52,53,55,57 that evaluated the effect of various educational interventions: provider education with feedback (k = 5); provider education without feedback (k = 2); patient education (k = 3); patient and provider education (k = 1); or patient and provider education with provider feedback (k = 1). The control groups were assigned either usual care (k = 10) or a sham intervention (i.e., targeting drugs that were not of interest, k = 2). Two trials were conducted in the USA, 3 in Canada, 6 in Europe, and 1 in Australia. We judged the risk of bias to be low in 6 trials and medium in the other 6. Outcomes were reported on a total of 3463 patients in the 9 smaller trials and on 252,684 in the 3 larger trials. Certainty of evidence for each primary outcome is summarized in Table 2.
All-cause mortality was reported in 6 trials (n = 121,314).18,21,22,23,24,30,40,53 None of the trials reported a difference between the intervention and control groups, and the data were not suitable for pooling due to heterogeneity of study interventions. Overall, educational interventions probably had no effect on all-cause mortality (moderate certainty).
Four of the 5 trials that reported hospitalizations found no difference between the intervention and control groups.21,22,23,24,40,53,57 Overall, education interventions probably do not reduce hospitalizations (moderate certainty).
Health-Related Quality of Life
Health-related quality of life was reported in 4 trials, none of which found a difference between the intervention and control groups.21,22,23,24,47,52 Overall, education interventions may have little to no effect on HRQoL (low certainty).
Two medium risk of bias trials reported falls and came to opposite conclusions. A US trial that randomized 169 people aged ≥ 65 at high risk for hospitalization or functional decline to enrollment in a chronic care clinic program or usual care. There was no difference in incidence of falls at 12 months between the 2 groups (43.5% vs 35.6%; P = .35).24 The second was an Australian trial that randomized 22 general practitioners to a provider education with feedback intervention or usual care.47 The physicians recruited 849 patients aged ≥ 65. At 12 months, the intervention group had lower odds of falls (OR: 0.61, 95% CI: 0.41 to 0.91; 20% vs 30%), injury (OR: 0.56, 95% CI: 0.32 to 0.96, 10% vs 18%), and injury requiring medical attention (OR: 0.46, 95% CI 0.30 to 0.70; 6% vs 13%). Overall, the effect of educational interventions on the risk of falls is not known (very low certainty).
Potentially Inappropriate Medications
All 11 trials that reported potentially inappropriate medications (PIMs) reported fewer PIMs in the intervention group than in the control group; the difference was statistically significant in 7 studies (Table 3).18,21,22,23,24,30,40,46,47,50,51,53,55,57
Computerized Decision Support
We identified 4 trials that evaluated the effect of computerized decision support.26,48,49,56 The interventions in these trials generally included electronic medical record alerts to pharmacists or providers identifying a PIM, sometimes with additional features such as a recommendation for a substitute medication. Two trials were conducted in the USA and 2 in Canada. Samples sizes ranged from 128 to 59,680 patients and study periods from 90 days to 13 months. All were considered medium risk of bias. In all 4 trials, reduction in PIMs was the only outcome reported (Table 3). Two reported a significant reduction of PIMs in the intervention group compared with the control group49,56 and 2 reported no intervention effect.26,48