Meta-analysis of Interventions to Reduce Adverse Drug Reactions in Older Adults

Shelly L. Gray, PharmD, MS; Laura A. Hart, PharmD; Subashan Perera, PhD; Todd P. Semla, PharmD, MS; Kenneth E. Schmader, MD; Joseph T. Hanlon, PharmD, MS


J Am Geriatr Soc. 2018;66(2):282-288. 

In This Article

Abstract and Introduction


Objectives To examine the effect of interventions to optimize medication use on adverse drug reactions (ADRs) in older adults.

Design Systematic review and meta-analysis. EMBASE, PubMed, OVID, Cochrane Library,, and Google Scholar were searched through April 30, 2017.

Setting Randomized controlled trials.

Participants Older adults (mean age ≥65) taking medications.

Measurements Two authors independently extracted relevant information and assessed studies for risk of bias. Discrepancies were resolved in consensus meetings. The outcomes were any and serious ADRs. Random-effects models were used to combine the results of multiple studies and create summary estimates.

Results Thirteen randomized controlled trials involving 6,198 older adults were included. The studies employed a number of different interventions that were categorized as pharmacist-led interventions (8 studies), other health professional-led interventions (3 studies), a brief educational session (1 study), and a technology intervention (1 study). The intervention group was 21% less likely than the control group to experience any ADR (odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.62–0.99). In the six studies that examined serious ADRs, the intervention group was 36% less likely than the control group to experience a serious ADR (OR = 0.64, 95% CI = 0.42–0.98).

Conclusion Interventions designed to optimize medication use reduced the risk of any and serious ADRs in older adults. Implementation of these successful interventions in healthcare systems may improve medication safety in older adults.


Adverse drug events (ADEs), defined as "an injury due to a medication," are a major public health problem for older adults.[1] Adverse drug reactions (ADRs), the most common subset of ADEs, are defined as "a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function" and excludes therapeutic failure and adverse drug withdrawal events.[2,3] A recent metaanalysis determined that nearly 9% of hospital admissions are due to ADRs in older adults.[4] Moreover, ADRs occur frequently in community-dwelling older adults (10–35% yearly), especially during transitions from higher levels of care such as after hospital discharge.[5,6] Polypharmacy is a consistent risk factor for ADRs.[7] Inappropriate prescribing and monitoring of medications further predispose older adults to ADRs.[8,9]

Prevention of ADRs in older adults is necessary because they worsen quality of life and increase healthcare system costs. Further evidence of their importance is the current federal initiative focused on ADR prevention efforts for the high-risk medication classes of anticoagulants, diabetes agents, and opioids.[10] However, there is a gap in the current literature regarding the effect that rigorously designed intervention studies have on reducing ADRs in older adults. A recent Cochrane review examined the effect of various interventions on inappropriate polypharmacy in older adults, but only 3 of the 12 included studies measured ADRs as secondary outcomes, which precluded conducting a meta-analysis.[11] A group from Ireland recently published two separate meta-analyses of the effect of pharmacist interventions on prescribing quality in older adults.[12,13] One focused on 5 studies conducted in primary care, but only one study examined ADRs as a secondary outcome.[12] The second focused on 4 interventions conducted in the inpatient setting, of which only two studies examined ADRs as a secondary outcome.[13] Only one meta-analysis in which ADRs were the primary outcome has been published.[14] It was limited in that none of the 6 included studies used a randomized controlled design, only one type of intervention was examined (in-hospital computerized order entry), and the effect in older adults was not examined.

Given this background, the objective of the current study was to examine the effect of interventions to optimize medication use on ADRs in older adults.