Overall, our review indicates that polypharmacy is common (33%) regardless of the definitions used to define it. Older age, inpatient clinical settings and cross-sectional study design were associated with an increased prevalence of polypharmacy. Our review also identified several definitions used to define polypharmacy in the literature. However, the term polypharmacy and a threshold of ≥ 2 medications were the most common definitions found in the literature. However, we did not find that these differing definitions significantly impacted the overall prevalence of polypharmacy in our meta-analysis.
To date, only one systematic review has addressed the multiple definitions of polypharmacy. In their review, Masnoon et al. identified 110 articles that assessed polypharmacy. However, in contrast to our study, Manson et al. did not incorporate a meta-analysis reporting the overall prevalence of polypharmacy or factors associated with polypharmacy. However, these authors highlighted the diverse range of terms used to define polypharmacy, such as minor, major, severe, excessive, hyper, appropriate, persistent, chronic, long term, and pseudo-polypharmacy. Both our review and this previous review highlight the variety of terms used to define polypharmacy and emphasize the need for researchers to create standardized definitions of polypharmacy in the future.
Awareness of polypharmacy is important as it is associated with several adverse outcomes such as the increased risk of drug-drug interactions, hospitalizations, functional decline and mortality.[11–14] When the number of prescribed medicines increases, the number of drug combinations increases exponentially, increasing the risk of adverse drug reactions and drug- drug interactions. Whether polypharmacy is directly causing these outcomes or if it is a marker for frailty or general vulnerability to poor outcomes is not always clear. However, the presence of polypharmacy may be an indicator for clinicians to identify individuals at risk for adverse outcomes who may benefit from preventative health measures and medication review. It has been suggested that different methods of measuring polypharmacy may have different clinical implications in this respect. To reduce adverse events or assess prescription appropriateness, cumulative indicators of polypharmacy may be more useful, whereas simultaneous assessments of polypharmacy may be more helpful for exploring drug-drug interactions. Continuous indicators may be more appropriate for assessing economic costs associated with polypharmacy or chronic disease burden measures. While our review could not incorporate contextual information related to comorbid medical conditions into our assessment of polypharmacy, this information is also critical to understanding if polypharmacy is appropriate or not at an individual level.
Several strategies can be employed to reduce inappropriate prescribing and/or polypharmacy. Medication review (by pharmacists, physicians, or multidisciplinary teams), education and training, and the use of screening tools to identify potentially inappropriate prescribing (e.g. Screening Tool of Older Persons’ Potentially Inappropriate Prescription (STOPP)) have all been found to be effective for reducing polypharmacy in various populations.[16–20] Digital technologies (for example, automatically generated alerts in electronic prescribing programs) have shown promising results in lowering polypharmacy in various settings but have not been widely adopted or investigated. Most of these studies focus on interventions to reduce polypharmacy in settings of greatest concern, such as among older adults or those in residential care settings. However, interventions to reduce polypharmacy vary widely, and the most effective aspects of interventions are still unclear. Deprescribing does not appear to increase adverse outcomes, but whether reducing polypharmacy results in better outcomes is questionable. Studies incorporating clinical outcomes have had mixed findings on the impact on the quality of life, falls, disease-specific outcomes, and hospitalizations.[17–20] Several reviews of interventions to reduce polypharmacy found no effect on all-cause mortality.[16, 18, 22]
Polypharmacy is a complex issue and may differ in appropriateness and implications for medically compromised individuals compared to those who are healthier. In general, polypharmacy needs to be justified and limited as much as possible, especially in older or frail adults. Several strategies have been proposed to reduce polypharmacy, such as deprescribing, reducing the use of unnecessary and inappropriate drugs, and underuse of medications. Still, their clinical significance is not well known. One of the main challenges is to disentangle the effects of removed drugs from reducing the overall burden of medicines that cause no harm. As well, the use of polypharmacy definitions in clinical practice and informatics systems depends on their operationalization and utility. Therefore, the evidence base of the suggested approaches merits more exploration.
This study is a novel and comprehensive review summarising the range of definitions and measurements of polypharmacy and alternative terms available in the literature. This is the first meta-analysis of polypharmacy prevalence. Our study included multiple electronic database searches and hand searching of bibliographies of included studies. This review also provided a high quality of evidence, as 95% of the included studies were at low risk of bias.
Despite these strengths, we acknowledge that this work has some limitations. Most studies operationalized polypharmacy as multiple medication use, so we could not distinguish between appropriate and inappropriate prescriptions. The prevalence estimates in this review were based mainly on raw and dispensing data available in some studies. The included studies did not use a homogenous, evidence-based approach to reporting the proportional rates of polypharmacy. This is likely one reason for the considerable heterogeneity observed across studies. While the observed difference among some subgroups was not significant, the high heterogeneity within those subgroups may reflect the presence of unmeasured factors influencing heterogeneity such as comorbidities, prescription patterns, medication dosage, or genetic factors. We could not obtain enough data from studies to examine these factors' effect on pooled estimates' variations.