- Open Access
Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis
BMC Geriatrics volume 22, Article number: 601 (2022)
Polypharmacy is commonly associated with adverse health outcomes. There are currently no meta-analyses of the prevalence of polypharmacy or factors associated with polypharmacy. We aimed to estimate the pooled prevalence of polypharmacy and factors associated with polypharmacy in a systematic review and meta-analysis.
MEDLINE, EMBASE, and Cochrane databases were searched for studies with no restrictions on date. We included observational studies that reported on the prevalence of polypharmacy among individuals over age 19. Two reviewers extracted study characteristics including polypharmacy definitions, study design, setting, geography, and participant demographics. The risk of bias was assessed using the Newcastle-Ottawa Scales. The main outcome was the prevalence of polypharmacy and factors associated with polypharmacy prevalence. The pooled prevalence estimates of polypharmacy with 95% confidence intervals were determined using random effects meta-analysis. Subgroup analyses were undertaken to evaluate factors associated with polypharmacy such as polypharmacy definitions, study setting, study design and geography. Meta-regression was conducted to assess the associations between polypharmacy prevalence and study year.
106 full-text articles were identified. The pooled estimated prevalence of polypharmacy in the 54 studies reporting on polypharmacy in all medication classes was 37% (95% CI: 31-43%). Differences in polypharmacy prevalence were reported for studies using different numerical thresholds, study setting, and publication year. Sex, study geography, study design and geographical location were not associated with differences in polypharmacy prevalence.
Our review highlights that polypharmacy is common particularly among older adults and those in inpatient settings. Clinicians should be aware of populations who have an increased likelihood of experiencing polypharmacy and efforts should be made to review the appropriateness of prescribed medications and occurrence of adverse effects potentially associated with polypharmacy.
Conclusions and implications
Clinicians should be aware of the common occurrence of polypharmacy and undertake efforts to minimize inappropriate polypharmacy whenever possible.
While medications are often necessary to manage acute and chronic health conditions, polypharmacy can be a significant problem related to prescribed medications. Polypharmacy refers to a situation where an individual uses multiple medications simultaneously. The World Health Organization (WHO) defines polypharmacy as “the administration of many drugs at the same time or the administration of an excessive number of drugs“ . While there is no consensus on the medication threshold and means of measurement, polypharmacy is often commonly defined as concomitant use of 5 or more medications [1, 2].
Prescribing multiple medications is often clinically required (appropriate polypharmacy). However, exposure to multiple medicines may lead to harm or the ongoing use of medications no longer indicated (inappropriate polypharmacy) [2, 3]. Polypharmacy can be associated with numerous poor health outcomes, especially among older adults with multimorbidity, including an increased risk of death, falls, drug interactions, non-adherence, and hospitalization [2, 3]. Polypharmacy has become a substantial health care burden. It is associated with an annual estimated cost of $50 billion US, which is increasing over time . To avoid such costs and potentially prevent adverse events associated with polypharmacy, identification of individuals who are at high risk of receiving inappropriate polypharmacy is an important first step .
Some research indicates that inappropriate polypharmacy can affect up to one-third of populations . However, an accurate estimate of the prevalence of polypharmacy requires the incorporation of information from multiple studies. Also, the factors associated with polypharmacy such as patient and healthcare characteristics have not been well-described. We conducted this systematic review and meta-analysis of population-based observational studies to estimate the prevalence of polypharmacy and identify factors associated with polypharmacy.
We registered our review protocol on PROSPERO (CRD42019130998). We followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for our systematic review .
Study inclusion criteria
We included population-based observational studies including all cross-sectional, case-control, or cohort designs using administrative databases or registries to define or measure polypharmacy among individuals over 19. We excluded studies that focused on children and adolescents (aged 0-18) as use of prescribed medications is relatively uncommon in these age groups. We included all publication dates and limited articles to the English language only. The primary study objective outcome was to estimate polypharmacy prevalence and identify factors associated with polypharmacy. We also identified definitions and measurements of polypharmacy using administrative databases or registries.
Search strategy and study selection
We developed a search strategy in consultation with a librarian specializing in health databases. We searched EMBASE, MEDLINE, and Cochrane Library from inception to March 30, 2019, using individualized search strategies prepared for each database. We limited results to studies conducted in humans and available in the English language. We used MeSH terms (e.g. polypharmacy, polytherapy, poly medication, poly prescription, multi medication, multi prescription, multidrug therapy, multiple drug treatment, multiple pharmacotherapies, administrative data, databases, registries) and combinations of relevant keywords and their variants by grouping polypharmacy and administrative database associated terms. The MEDLINE search strategy is presented in Additional file 1 and this was adapted for the other databases. We also hand-searched for additional publications using a reference list of relevant papers. Reference management and citation screening were performed using EndNote™ (V.X7) . Using a two-step process for study selection, two of three reviewers (MD, LM) independently screened each citation’s title and abstract to determine whether a study met the inclusion criteria. The full texts of all relevant citations were retrieved for formal review. Two reviewers (MD, LM) independently assessed the full-text reports. Conflicts were resolved by discussion between reviewers.
Data extraction and management
We created a standardized data extraction form and piloted and modified the form for our review. Two reviewers (MD, LM) extracted data independently, using this form, with conflicts resolved through consensus. The extracted study characteristics included study identifiers, study country, year of publication, sample size, setting, study design, and age and sex of participants. The prevalence of polypharmacy was extracted from each study using the numerator and denominator of the number of participants meeting polypharmacy criteria and the total study sample. Information on the definitions of polypharmacy used in individual studies were recorded including the medication cut-offs used to define polypharmacy, the time period of polypharmacy assessment, the number of overlapping days, and terminology used to define polypharmacy.
We assessed the risk of bias and quality of the included studies using the Newcastle-Ottawa Scales for cross-sectional, cohort and case control studies . These tools consist of 7 to 8 domains depending on the type of study design; each domain is rated ‘low risk,’ ‘unclear risk,’ or ‘high risk.’ Studies were categorized based on total scores as being of either high quality (total scores ≥7) or low quality (total score < 7).
The included studies’ data were summarized in frequency tables and analyzed using RStudio (version 3.6.1). Meta-analyses were performed using random effects models using inverse variance weighting. Meta-analysis was used to estimate of the pooled prevalence of polypharmacy and 95% confidence intervals (CI). Heterogeneity was determined using the I-squared (I2) statistic and categorized as low < 25%, moderate 25–50%, high > 50% heterogeneity . If significant heterogeneity was suspected, further analysis, including subgroup analysis, was conducted to explore potential sources of heterogeneity. We used meta-regression analysis to assess the associations between polypharmacy prevalence and publication year. Subgroup analysis of age was performed using either the mean age of the study population or the median age of the study population depending on which measure of age was reported in individual studies and we categorized age as < 65 years or ≥ 65 years. Publication bias was assessed for the prevalence of polypharmacy using funnel plots and Egger’s test .
We restricted subgroup analyses to situations where a minimum of 4 studies were available for each categorical study-level variable . A total of nine subgroup analyses were planned based on: mean age (< 65 vs ≥ 65 years); sex of participants (male vs female), geography of study (Europe, Asia, North America, Australia, South America, Africa), health care setting (inpatient vs outpatient vs community), study design (cross-sectional vs case-control vs cohort), methodological quality (low vs high); medication threshold (2 vs 5), measurement indicator (simultaneous vs cumulative).
Of 525 unique citations, we retrieved and reviewed 179 full text articles. Of these full text articles, 106 studies met inclusion criteria [1, 11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115]. The studies were published from 1989 to 2019. Figure 1 depicts a PRISMA flowchart of citations reviewed. The baseline characteristics of studies are summarized in Additional File 2. While two studies were multicentre, most studies were conducted in Europe (n = 59), followed by Asia (n = 21), North America (n = 20), Australia (n = 2), and South America (n = 2). The healthcare setting was specified in 50 studies (49.1%) including community (n = 15), inpatient (n = 15), outpatient (n = 13) or a combination of these settings (n = 7). Nearly 75% percent of the studies were cross-sectional (n = 80). The studies included a different number of participants varying from 248 to 12,301,537 individuals. The mean age of participants ranged from 26 to 87 years old.
Definitions of polypharmacy
Fifty-seven studies used the term polypharmacy (n = 57, 54%) followed by polytherapy (n = 18 studies, 17%), co-prescribing (2 studies,1.9%), multiple medication use (1 study, 0.9%), concurrent medication (1 study, 0.9%), poly medication (1 study, 0.9%), concomitant use (1 study, 0.9%) and comedication (1 study, 0.9%) (Additional File 3). Out of the 106 identified articles, 96 (90.6%) included information on the number of medications required for a definition of polypharmacy resulting in 124 different definitions with the remaining studies not reporting a specific medication threshold. Among studies reporting a medication threshold the threshold for polypharmacy varied between 2 and 21 medications. A medication threshold of ≥5 medications was the most commonly used threshold (52 studies, 49%) followed by a threshold of ≥2 medications (39 studies, 37%). All descriptive definitions had a time component, including the duration of therapy, minimum days of overlap, time interval, or assessment frequency. Three studies expressly incorporated an allowable gap of 12, 14, and 15 days in their definitions, and one study reported a grace period of 28 days.
The definitions used for polypharmacy varied across studies with 59 studies using a simultaneous approach (55.7%), 45 using the cumulative method (42.5%), and two studies examined a combination of simultaneous and cumulative approaches (1.9%) (Additional file 3). Studies using a simultaneous definition of polypharmacy required 2 or more medications to be prescribed concurrently. The most common duration of concurrent use was described in studies using the concurrent approach was at least 1 day overlap between medications (47 studies, 44%). The minimum overlap days required for the simultaneous approach ranged from 1 day to 1 year. Cumulative definitions assessed the number of unique medications prescribed at any time during a specified time period without requiring the medications to be overlapping for the entire time period. Among studies using a cumulative approach, a 90-day time period was identified as the most duration in which cumulative medications were prescribed (9 studies, 9%). The timing of polypharmacy assessment also differed across studies. Studies using the cumulative approach specified a period between 14 to 730 days.
Prevalence of polypharmacy
Nighty-four studies (100 single reports) contained sufficient quantitative information to determine the prevalence of polypharmacy. Of the 94 studies, 54 reported on polypharmacy incorporating all medications. The remaining studies only reported polypharmacy related to specific medication classes (e.g. psychotropic polypharmacy, polypharmacy with antiepileptic medications). The pooled estimated prevalence of polypharmacy among the 54 studies reporting on polypharmacy including all medications was 37% (95% CI: 31 - 43%). There was a high degree of heterogeneity observed in this estimate (Tau2=0.0424, Chi2=22,194,826, df = 53, I2 = 100%) (Fig. 2). Due to the heterogeneity in the definitions of polypharmacy used in other studies we did not include studies that did not report on the prevalence of polypharmacy using all medication classes.
Factors associated with polypharmacy
Subgroup analyses were undertaken using the studies reporting polypharmacy including all medication classes. These subgroup analyses included sex, numerical threshold (≥2 medications vs ≥5 medications), study geography (North America vs other), study design (cross-sectional, case-control, or cohort) and study setting (community, outpatient and inpatient) or study location (North America vs outside North America). Meta-regression was used to assess the associations between polypharmacy and study year. A summary of the results of the subgroup analyses are provided in Table 1.
Subgroup analysis by age indicated that studies with a population age of ≥65 years were associated with a higher prevalence of polypharmacy (45, 95% CI: 37 to 54%) when compared to studies with population age of < 65 years (25, 95% CI: 15 - 35%, P < 0.01, Additional file 4). Studies using a threshold of ≥2 medications had a lower reported prevalence of polypharmacy (22, 95% CI: 10 - 35%, N = 9) when compared to studies using a threshold of ≥5 medications (40, 95% CI: 0 – 47%; N = 43; P < 0.01, Additional file 5). There was also a significant difference in the estimates of polypharmacy between health care settings with lower estimates of polypharmacy associated with community settings (20, 95% CI: 6 - 35%) when compared to outpatient (37, 95% CI: 33 - 66%) and hospital settings (52, 95% CI: 38 - 66%, Additional file 6). There were no differences in polypharmacy prevalence in subgroup analyses based on sex (Additional file 7), or geographical location (Additional file 8) or study design (Additional file 9).
Meta-regression demonstrated that more recent studies were associated with a higher prevalence of polypharmacy (β estimate = 0.0175, p = 0.003).
Assessment of study quality
Studies were overall adjudicated to be at low risk of bias or high quality (101 studies, 95.3%), and five studies were judged to be at high risk of bias or low quality. The assessment of study quality according to the Newcastle-Ottawa Scale risk of bias assessments for cohort, case-control and cross-sectional studies are provided in Additional file 10. Overall, 10/13 cohort (77%), 11/13 of case-control (85%) and 80/80 cross-sectional studies (100%) were reported to be of high quality.
Publication Bias assessment
The Egger’s test for publication bias did not indicate any potential evidence of publication bias (t = 2.06, d.f. 52, P = 0.05) and the funnel plot is presented in Additional File 11.
Overall, our review indicates that polypharmacy is common with an estimated overall prevalence of 37%. Older age, inpatient clinical settings and more recent studies were associated with a higher prevalence of polypharmacy. Our review also identified several definitions used to define polypharmacy in the literature with the term polypharmacy and a threshold of ≥5 medications were the most common definitions found in the literature. While our review could not incorporate contextual information related to comorbid medical conditions into our assessment of polypharmacy, this information is also necessary to understanding if polypharmacy is appropriate or inappropriate not for an individual which is critical to optimizing prescribing of medications and balancing potential benefits and risks associated with the prescribing of multiple medications.
Our review provides new information about patient populations at high risk for experiencing polypharmacy particularly older adults and those in outpatient or hospital inpatient settings. Clinicians should be aware of the high prevalence of polypharmacy particularly in these contexts and consider implementing processes to review medications for their appropriateness to reduce potential adverse effects from inappropriate polypharmacy. 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 [116,117,118,119]. 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.
Our review identified several different terms and thresholds are used to define polypharmacy consistent with a related review on this topic . Masnoon et al.  identified 110 articles that assessed 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 . Our review identified that different medication thresholds may impact on the estimates of polypharmacy. While we did not observe any difference in the estimated prevalence of polypharmacy using continuous or simultaneous approaches to defining polypharmacy it has been suggested that different methods of measuring polypharmacy may have different clinical implications . Simultaneous assessments of polypharmacy may be more helpful for exploring outcomes potentially adverse events directly related to drug-drug interactions as simultaneous polypharmacy assesses concurrent use of medications at the same time. Cumulative measures of polypharmacy may help identify potential risks associated with polypharmacy during a period of time which may also be associated with adverse outcomes or reflect changes to individual’s clinical status over time. Both our review and this previous review highlight the variety of terms used to define polypharmacy and emphasize the need for researchers to employ standardized definitions of polypharmacy in the future including incorporating information about inappropriate polypharmacy. Further study is also required to understand if different definitions of polypharmacy are associated with different risks of adverse outcomes.
Identifying any polypharmacy is the first step towards assessing whether polypharmacy is inappropriate. Several strategies can be employed to reduce inappropriate prescribing or inappropriate 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 [121,122,123,124,125,126]. 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 improved outcomes is not as clear. Studies incorporating clinical outcomes have had mixed findings on the effects of deprescribing on the quality of life, falls, disease-specific outcomes, and hospitalizations . Several reviews of interventions to reduce polypharmacy found no effect on all-cause mortality [121, 123, 127].
Polypharmacy is a complex issue and may differ in appropriateness and implications for medically complex 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 removing drugs from reducing the overall burden of medicines that are not causing harm or adverse events . As well, the use of polypharmacy definitions in clinical practice and informatics systems depends on their operationalization and utility . Therefore, the best approaches to addressing polypharmacy in different contexts and populations requires further consideration.
Our study has several strengths. By conducting a meta-analysis of the prevalence of polypharmacy which helps provide a better understanding of the frequency of polypharmacy. Our review also highlights important factors associated with the prevalence of polypharmacy which previously had primarily been described in individual studies. Our search strategy identified over 100 studies reporting on polypharmacy which will help produce less biased estimates of the prevalence of polypharmacy. Our review also identified that there is a relatively high quality of evidence on this topic, as the majority of 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 polypharmacy. The prevalence estimates in this review were based mainly on dispensing data and adherence to prescribed medications was not available in studies. The included studies did not use a homogenous study populations or polypharmacy which contributed to 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, adherence, medication dosage or other factors which may also influence estimates of polypharmacy. We also only included studies that used administrative or registry data which may have excluded some studies on polypharmacy which used alternative sources of data.
Conclusion and implications
Our study highlights that polypharmacy is common among adults particularly among older adults and those in inpatient settings. Given the adverse outcomes potentially associated with polypharmacy, it is important to understand both the prevalence of polypharmacy and those populations at highest risk for being exposed to polypharmacy. Clinicians should regularly assess patients for the presence of polypharmacy and institute measures to reduce inappropriate polypharmacy when it is possible to do so. Efforts should continue to be made to harmonize definitions of polypharmacy to facilitate more consistent reporting of polypharmacy in the research literature and information on the appropriateness of polypharmacy should be incorporated into reporting of polypharmacy in future studies.
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Preferred Reporting Items for Systematic Reviews and Meta-analysis
Screening Tool of Older Persons’ Potentially Inappropriate Prescription
Monégat M, Sermet C, Perronnin M, Rococo E. Polypharmacy: definitions, measurement and stakes involved - review of the literature and measurement tests. Quest d’économie la Santé. 2014;204:1–8.
Davies LE, Spiers G, Kingston A, Todd A, Adamson J, Hanratty B. Adverse outcomes of polypharmacy in older people: systematic review of reviews. J Am Med Dir Assoc. 2020;21(2):181–7. https://doi.org/10.1016/j.jamda.2019.10.022.
Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):1–10. https://doi.org/10.1186/s12877-017-0621-2.
Moriarty F, Hardy C, Bennett K, Smith SM, Fahey T. Trends and interaction of polypharmacy and potentially inappropriate prescribing in primary care over 15 years in Ireland: a repeated cross-sectional study. BMJ Open. 2015;5(9):1–7. https://doi.org/10.1136/bmjopen-2015-008656.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–41. https://doi.org/10.1371/journal.pmed.1000097.
Superior Business Solutions. EndNote solution: Your smarter way to research. 2021. https://sbs-me.com/blogs/endnote-your-smarter-way-to-research/ Accessed May 4, 2021.
Wells GA, Shea B, Da O’C, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2011.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58. https://doi.org/10.1002/sim.1186.
Ioannidis JP, Trikalinos TA. The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. Can Med Assoc J. 2007;176(8):1091–6. https://doi.org/10.1503/cmaj.060410.
Fu R, Gartlehner G, Grant M, Shamliyan T, Sedrakyan A, Wilt TJ, et al. Conducting quantitative synthesis when comparing medical interventions: AHRQ and the effective health care program. J Clin Epidemiol. 2011;64(11):1187–97. https://doi.org/10.1016/j.jclinepi.2010.08.010.
Källén B, Robert E, Mastroiacovo P, Martinez-Frias M, Castilla E, Cocchi G. Anticonvulsant drugs and malformations is there a drug specificity? Eur J Epidemiol. 1989;5(1):31–6. https://doi.org/10.1007/BF00145041.
Bjerrum L, Rosholm J, Hallas J, Kragstrup J. Methods for estimating the occurrence of polypharmacy by means of a prescription database. Eur J Clin Pharmacol. 1997;53(1):7–11. https://doi.org/10.1007/s002280050329.
Bjerrum L, Søgaard J, Hallas J, Kragstrup J. Polypharmacy: correlations with sex, age and drug regimen: a prescription database study. Eur J Clin Pharmacol. 1998;54(3):197–202. https://doi.org/10.1007/s002280050445.
Veehof L, Stewart R, Haaijer-Ruskamp F, Jong BM-d. The development of polypharmacy. A longitudinal study. Fam Pract. 2000;17(3):261–7. https://doi.org/10.1093/fampra/17.3.261.
Weissman EM. Antipsychotic prescribing practices in the veterans healthcare administration-New York metropolitan region. Schizophr Bull. 2002;28(1):31–42. https://doi.org/10.1093/oxfordjournals.schbul.a006924.
Hamann J, Ruppert A, Auby P, Pugner K, Kissling W. Antipsychotic prescribing patterns in Germany: a retrospective analysis using a large outpatient prescription database. Int Clin Psychopharmacol. 2003;18(4):237–42.
Jaffe AB, Levine J. Antipsychotic medication coprescribing in a large state hospital system. Pharmacoepidemiol Drug Saf. 2003;12(1):41–8. https://doi.org/10.1002/pds.783.
De las Cuevas C, Sanz EJ. Polypharmacy in psychiatric practice in the Canary Islands. BMC Psychiatry. 2004;4(1):1–8. https://doi.org/10.1186/1471-244X-4-18.
Malm H, Martikainen J, Klaukka T, Neuvonen PJ. Prescription of hazardous drugs during pregnancy. Drug Saf. 2004;27(12):899–908. https://doi.org/10.2165/00002018-200427120-00006.
French DD, Campbell R, Spehar A, Cunningham F, Foulis P. Outpatient medications and hip fractures in the US. Drugs Aging. 2005;22(10):877–85. https://doi.org/10.2165/00002512-200522100-00006.
Preskorn SH, Silkey B, Shah R, Neff M, Jones TL, Choi J, et al. Complexity of medication use in the veterans affairs healthcare system: part I: outpatient use in relation to age and number of prescribers. J Psychiatr Pract. 2005;11(1):5–15.
Åstrand B, Åstrand E, Antonov K, Petersson G. Detection of potential drug interactions – a model for a national pharmacy register. Eur J Clin Pharmacol. 2006;62(9):749–56. https://doi.org/10.1007/s00228-006-0143-x.
Åstrand E, Åstrand B, Antonov K, Petersson G. Potential drug interactions during a three-decade study period: a cross-sectional study of a prescription register. Eur J Clin Pharmacol. 2007;63(9):851–9. https://doi.org/10.1007/s00228-007-0326-0.
Targownik LE, Metge C, Roos L, Leung S. The prevalence of and the clinical and demographic characteristics associated with high-intensity proton pump inhibitor use. Am J Gastroenterol. 2007;102(5):942–50.
Carey IM, De Wilde S, Harris T, Victor C, Richards N, Hilton SR, et al. What factors predict potentially inappropriate primary care prescribing in older people? Drugs Aging. 2008;25(8):693–706. https://doi.org/10.2165/00002512-200825080-00006.
Dolk H, Jentink J, Loane M, Morris J, de Jong–van den Berg LT. Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology. 2008;71(10):714–22. https://doi.org/10.1212/01.wnl.0000316194.98475.d8.
Gidal BE, French JA, Grossman P, Le Teuff G. Assessment of potential drug interactions in patients with epilepsy: impact of age and sex. Neurology. 2009;72(5):419–25. https://doi.org/10.1212/01.wnl.0000341789.77291.8d.
Haider SI, Johnell K, Weitoft GR, Thorslund M, Fastbom J. The influence of educational level on polypharmacy and inappropriate drug use: a register-based study of more than 600,000 older people. J Am Geriatr Soc. 2009;57(1):62–9. https://doi.org/10.1111/j.1532-5415.2008.02040.x.
Hsieh L-P, Huang C-Y. Antiepileptic drug utilization in Taiwan: analysis of prescription using National Health Insurance database. Epilepsy Res. 2009;84(1):21–7. https://doi.org/10.1016/j.eplepsyres.2008.11.018.
Constantine RJ, Andel R, Tandon R. Trends in adult antipsychotic polypharmacy: Progress and challenges in Florida’s Medicaid program. Community Ment Health J. 2010;46(6):523–30. https://doi.org/10.1007/s10597-009-9288-2.
Hovstadius B, Hovstadius K, Åstrand B, Petersson G. Increasing polypharmacy-an individual-based study of the Swedish population 2005-2008. BMC Clin Pharmacol. 2010;10(1):1–8. https://doi.org/10.1186/1472-6904-10-16.
Lai S-W, Liao K-F, Liao C-C, Muo C-H, Liu C-S, Sung F-C. Polypharmacy correlates with increased risk for hip fracture in the elderly: a population-based study. Medicine. 2010;89(5):295–9. https://doi.org/10.1097/MD.0b013e3181f15efc.
Moisan J, Grégoire J-P. Patterns of discontinuation of atypical antipsychotics in the province of Québec: a retrospective prescription claims database analysis. Clin Ther. 2010;32:S21–31. https://doi.org/10.1016/j.clinthera.2010.01.003.
Slabaugh SL, Maio V, Templin M, Abouzaid S. Prevalence and risk of polypharmacy among the elderly in an outpatient setting. Drugs Aging. 2010;27(12):1019–28. https://doi.org/10.2165/11584990-000000000-00000.
Charlton RA, Weil JG, Cunnington MC, Ray S, de Vries CS. Comparing the general practice research database and the UK epilepsy and pregnancy register as tools for post marketing teratogen surveillance. Drug Saf. 2011;34(2):157–71. https://doi.org/10.2165/11584970-000000000-00000.
Hoffmann F, van den Bussche H, Wiese B, Schön G, Koller D, Eisele M et al. Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia. BMC Psychiatry 2011; 11(1):1–8. https://doi.org/10.1186/1471-244X-11-190.
Kragh A, Elmståhl S, Atroshi I. Older adults' medication use 6 months before and after hip fracture: a population-based cohort study. J Am Geriatr Soc. 2011;59(5):863–8. https://doi.org/10.1111/j.1532-5415.2011.03372.x.
Kulaga S, Sheehy O, Zargarzadeh AH, Moussally K, Bérard A. Antiepileptic drug use during pregnancy: perinatal outcomes. Seizure. 2011;20(9):667–72. https://doi.org/10.1016/j.seizure.2011.06.012.
Lai SW, Su LT, Lin CH, Tsai CH, Sung FC, Hsieh DPH. Polypharmacy increases the risk of Parkinson's disease in older people in Taiwan: a population-based study. Psychogeriatrics. 2011;11(3):150–6. https://doi.org/10.1111/j.1479-8301.2011.00369.x.
Landmark CJ, Fossmark H, Larsson PG, Rytter E, Johannessen SI. Prescription patterns of antiepileptic drugs in patients with epilepsy in a nation-wide population. Epilepsy Res. 2011;95(1-2):51–9. https://doi.org/10.1016/j.eplepsyres.2011.02.012.
Pergolizzi JV Jr, Labhsetwar SA, Puenpatom RA, Joo S, Ben-Joseph R, Summers KH. Exposure to potential CYP450 pharmacokinetic drug–drug interactions among osteoarthritis patients: incremental risk of multiple prescriptions. Pain Pract. 2011;11(4):325–36. https://doi.org/10.1111/j.1533-2500.2010.00438.x.
Sanglier T, Saragoussi D, Milea D, Auray JP, Valuck RJ, Tournier M. Comparing antidepressant treatment patterns in older and younger adults: a claims database analysis. J Am Geriatr Soc. 2011;59(7):1197–205. https://doi.org/10.1111/j.1532-5415.2011.03457.x.
Andrew T, Milinis K, Baker G, Wieshmann U. Self reported adverse effects of mono and polytherapy for epilepsy. Seizure. 2012;21(8):610–3. https://doi.org/10.1016/j.seizure.2012.06.013.
Baandrup L, Sørensen J, Lublin H, Nordentoft M, Glenthoj B. Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis. Eur J Health Econ. 2012;13(3):355–63. https://doi.org/10.1007/s10198-011-0308-0.
Lai SW, Lin CH, Liao KF, Su LT, Sung FC, Lin CC. Association between polypharmacy and dementia in older people: a population-based case–control study in Taiwan. Geriatr Gerontol Int. 2012;12(3):491–8. https://doi.org/10.1111/j.1447-0594.2011.00800.x.
Tiihonen J, Suokas JT, Suvisaari JM, Haukka J, Korhonen P. Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry. 2012;69(5):476–83. https://doi.org/10.1001/archgenpsychiatry.2011.1532.
Xiang Y-T, Dickerson F, Kreyenbuhl J, Ungvari GS, Wang C-Y, Si T-M, et al. Common use of antipsychotic polypharmacy in older Asian patients with schizophrenia (2001–2009). J Clin Psychopharmacol. 2012;32(6):809–13. https://doi.org/10.1097/JCP.0b013e3182726623.
Blozik E, Rapold R, von Overbeck J, Reich O. Polypharmacy and potentially inappropriate medication in the adult, community-dwelling population in Switzerland. Drugs Aging. 2013;30(7):561–8. https://doi.org/10.1007/s40266-013-0073-0.
Calderón-Larrañaga A, Gimeno-Feliu LA, González-Rubio F, Poblador-Plou B, Lairla-San José M, Abad-Díez JM, et al. Polypharmacy patterns: unravelling systematic associations between prescribed medications. PLoS One. 2013;8(12):e84967. https://doi.org/10.1371/journal.pone.0084967.
Curkendall SM, Thomas N, Bell KF, Juneau PL, Weiss AJ. Predictors of medication adherence in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2013;29(10):1275–86. https://doi.org/10.1185/03007995.2013.821056.
Franchi C, Cartabia M, Risso P, Mari D, Tettamanti M, Parabiaghi A, et al. Geographical differences in the prevalence of chronic polypharmacy in older people: eleven years of the EPIFARM-elderly project. Eur J Clin Pharmacol. 2013;69(7):1477–83. https://doi.org/10.1007/s00228-013-1495-7.
Gören JL, Meterko M, Williams S, Young GJ, Baker E, Chou C-H, et al. Antipsychotic prescribing pathways, polypharmacy, and clozapine use in treatment of schizophrenia. Psychiatr Serv. 2013;64(6):527–33. https://doi.org/10.1176/appi.ps.002022012.
Lizano-Díez I, Modamio P, López-Calahorra P, Lastra CF, Gilabert-Perramon A, Segú JL, et al. Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia. Spain BMJ Open. 2013;3(12):e003963. https://doi.org/10.1136/bm.jopen-2013-003963.
Onishi Y, Hinotsu S, Furukawa TA, Kawakami K. Psychotropic prescription patterns among patients diagnosed with depressive disorder based on claims database in Japan. Clin Drug Investig. 2013;33(8):597–605. https://doi.org/10.1007/s40261-013-0104-y.
Palmsten K, Huybrechts KF, Michels KB, Williams PL, Mogun H, Setoguchi S, et al. Antidepressant use and risk for preeclampsia. Epidemiology. 2013;24(5):682–91. https://doi.org/10.1097/EDE.0b013e31829e0aaa.
Ruwald MH, Hansen ML, Lamberts M, Hansen CM, Numé A-K, Vinther M, et al. Comparison of incidence, predictors, and the impact of co-morbidity and polypharmacy on the risk of recurrent syncope in patients< 85 versus≥ 85 years of age. Am J Cardiol. 2013;112(10):1610–5. https://doi.org/10.1016/j.amjcard.2013.07.041.
Suokas JT, Suvisaari JM, Haukka J, Korhonen P, Tiihonen J. Description of long-termpolypharmacy among schizophrenia outpatients. Soc Psychiatry Psychiatr Epidemiol. 2013;48(4):631–8. https://doi.org/10.1007/s00127-012-0586-6.
Wong MC, Tam WW, Cheung CS, Tong EL, Sek AC, Cheung N, et al. Antihypertensive prescriptions over a 10-year period in a large Chinese population. Am J Hypertens. 2013;26(7):931–8. https://doi.org/10.1093/ajh/hpt049.
Degli Esposti L, Sangiorgi D, Mencacci C, Spina E, Pasina C, Alacqua M, et al. Pharmaco-utilisation and related costs of drugs used to treat schizophrenia and bipolar disorder in Italy: the IBIS study. BMC Psychiatry. 2014;14(1):1–9. https://doi.org/10.1186/s12888-014-0282-z.
Fano V, Chini F, Pezzotti P, Bontempi K. Estimating the prevalence and the determinants of polypharmacy using data from a health administrative database: a comparison of results obtained employing different algorithms. Adv. Pharmacoepidemiol Drug Saf. 2014;3(151):2167–1052.10001. https://doi.org/10.4172/2167-1052.1000151.
Fereshtehnejad S-M, Johnell K, Eriksdotter M. Anti-dementia drugs and co-medication among patients with Alzheimer’s disease. Drugs Aging. 2014;31(3):215–24. https://doi.org/10.1007/s40266-014-0154-8.
Franchi C, Tettamanti M, Pasina L, Djignefa CD, Fortino I, Bortolotti A, et al. Changes in drug prescribing to Italian community-dwelling elderly people: the EPIFARM–elderly project 2000–2010. Eur J Clin Pharmacol. 2014;70(4):437–43. https://doi.org/10.1007/s00228-013-1621-6.
Frandsen R, Baandrup L, Kjellberg J, Ibsen R, Jennum P. Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls: a national register-based study. Parkinsonism Relat Disord. 2014;20(11):1124–8. https://doi.org/10.1016/j.parkreldis.2014.07.012.
Gamble J-M, Hall JJ, Marrie TJ, Sadowski CA, Majumdar SR, Eurich DT. Medicationtransitions and polypharmacy in older adults following acute care. Ther Clin Risk Manag. 2014;10:189–96. https://doi.org/10.2147/TCRM.S58707.
Guidoni CM, Obreli-Neto PR, Pereira LRL. Pharmacoepidemiologic study of warfarin prescription in a Brazilian tertiary hospital. J Thromb Thrombolysis. 2014;37(4):542–8. https://doi.org/10.1007/s11239-013-1030-9.
Helgadóttir B, Laflamme L, Monárrez-Espino J, Möller J. Medication and fall injury in theelderly population: do individual demographics, health status and lifestyle matter? BMC Geriatr. 2014;14(1):1–8. https://doi.org/10.1186/1471-2318-14-92.
Hovstadius B, Petersson G, Hellström L, Ericson L. Trends in inappropriate drug therapy prescription in the elderly in Sweden from 2006 to 2013: assessment using national indicators. Drugs Aging. 2014;31(5):379–86. https://doi.org/10.1007/s40266-014-0165-5.
Kim H-A, Shin J-Y, Kim M-H, Park B-J. Prevalence and predictors of polypharmacy among Korean elderly. PLoS One. 2014;9(6):e98043. https://doi.org/10.1371/journal.pone.0098043.
Onder G, Bonassi S, Abbatecola AM, Folino-Gallo P, Lapi F, Marchionni N, et al. High prevalence of poor quality drug prescribing in older individuals: a nationwide report from the Italian Medicines Agency (AIFA). J Gerontol A Biol Sci Med Sci. 2014;69(4):430–7. https://doi.org/10.1093/gerona/glt118.
Pottegård A, Christensen R, Houji A, Christiansen CB, Paulsen MS, Thomsen JL, et al. Primary non-adherence in general practice: a Danish register study. Eur J Clin Pharmacol. 2014;70(6):757–63. https://doi.org/10.1007/s00228-014-1677-y.
Rossini M, Viapiana O, Adami S, Idolazzi L, Buda S, Veronesi C, et al. Medication use before and after hip fracture: a population-based cohort and case-control study. Drugs Aging. 2014;31(7):547–53. https://doi.org/10.1007/s40266-014-0184-2.
Wang L-J, Chen Y-C, Chen C-K, Chou W-J, Chou M-C. Trends in anxiolytic-hypnotic use and polypharmacy in Taiwan, 2002–2009: a nationwide, population-based survey. Psychiatr Serv. 2014;65(2):208–14. https://doi.org/10.1176/appi.ps.201300066.
Gaviria AM, Franco JG, Aguado V, Rico G, Labad J, de Pablo J, et al. A non-interventional naturalistic study of the prescription patterns of antipsychotics in patients with schizophrenia from the Spanish Province of Tarragona. PLoS One. 2015;10(10):e0139403. https://doi.org/10.1371/journal.pone.0139403.
Laflamme L, Monárrez-Espino J, Johnell K, Elling B, Möller J. Type, number or both? Apopulation-based matched case-control study on the risk of fall injuries among older people and number of medications beyond fall-inducing drugs. PLoS One. 2015;10(3):e0123390. https://doi.org/10.1371/journal.pone.0123390.
Lin S-K, Tsai Y-T, Lai J-N, Wu C-T. Demographic and medication characteristics of traditional Chinese medicine users among dementia patients in Taiwan: a nationwide database study. J Ethnopharmacol. 2015;161:108–15. https://doi.org/10.1016/j.jep.2014.12.015.
Lu W-H, Wen Y-W, Chen L-K, Hsiao F-Y. Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study. Can Med Assoc J. 2015;187(4):E130–7. https://doi.org/10.1503/cmaj.141219.
Salahudeen MS, Hilmer SN, Nishtala PS. Comparison of anticholinergic risk scales and associations with adverse health outcomes in older people. J Am Geriatr Soc. 2015;63(1):85–90. https://doi.org/10.1111/jgs.13206.
van de Vorst I, Vaartjes I, Sinnecker L, Beks L, Bots M, Koek H. The validity of national hospital discharge register data on dementia: a comparative analysis using clinical data from a university medical Centre. Neth J Med. 2015;73(2):69–75.
Baandrup L, Kruse M. Incident users of antipsychotics: who are they and how do they fare? Soc Psychiatry Psychiatr Epidemiol. 2016;51(4):505–12. https://doi.org/10.1007/s00127-015-1129-8.
Chang C-M, Wu C-S, Huang Y-W, Chau Y-L, Tsai H-J. Utilization of psychopharmacological treatment among patients with newly diagnosed bipolar disorder from 2001 to 2010. J Clin Psychopharmacol. 2016;36(1):32–44. https://doi.org/10.1097/JCP.0000000000000440.
Ekstam AK, Elmståhl S. Do fall-risk-increasing drugs have an impact on mortality in older hip fracture patients? A population-based cohort study. Clin Interv Aging. 2016;11:489–96. https://doi.org/10.2147/CIA.S101832.
Horváth L, Fekete K, Márton S, Fekete I. Outcome of antiepileptic drug treatment of 1282 patients with epilepsy, their pharmacovigilance reports and concomitant medication on CNS inan east-Hungarian adult database. J Neurol Sci. 2016;369:220–6. https://doi.org/10.1016/j.jns.2016.08.039.
Sinnige J, Braspenning JC, Schellevis FG, Hek K, Stirbu I, Westert GP, et al. Inter-practice variation in polypharmacy prevalence amongst older patients in primary care. Pharmacoepidemiol Drug Saf. 2016;25(9):1033–41. https://doi.org/10.1002/pds.4016.
van den Bemt PM, Chaaouit N, van Lieshout EM, Verhofstad MH. Noncompliance with guidelines on proton pump inhibitor prescription as gastroprotection in hospitalized surgical patients who are prescribed NSAIDs. Eur J Gastroenterol Hepatol. 2016;28(8):857–62. https://doi.org/10.1097/MEG.0000000000000634.
van Erning F, Zanders M, Kuiper J, van Herk-Sukel M, Maas H, Vingerhoets R, et al. Drug dispensings among elderly in the year before colon cancer diagnosis versus matched cancer-free controls. J Clin Pharm Ther. 2016;41(5):538–45. https://doi.org/10.1111/jcpt.12434.
Abe J, Umetsu R, Uranishi H, Suzuki H, Nishibata Y, Kato Y, et al. Analysis of polypharmacy effects in older patients using Japanese adverse drug event report database. PLoS One. 2017;12(12):e0190102. https://doi.org/10.1371/journal.pone.0190102.
Broeks SC, Horsdal HT, Ingstrup KG, Gasse C. Psychopharmacological drug utilization patterns in pregnant women with bipolar disorder – a nationwide register-based study. J Affect Disord. 2017;210(Supplement 3):158–65. https://doi.org/10.1016/j.jad.2016.12.001.
Byrne CJ, Cahir C, Curran C, Bennett K. High-risk prescribing in an Irish primary care population: trends and variation. Br J Clin Pharmacol. 2017;83(12):2821–30. https://doi.org/10.1111/bcp.13373.
Caughey G, Barratt J, Shakib S, Kemp-Casey A, Roughead E. Medication use and potentially high-risk prescribing in older patients hospitalized for diabetes: a missed opportunity to improvecare? Diabet Med. 2017;34(3):432–9. https://doi.org/10.1111/dme.13148.
Feng X, Tan X, Riley B, Zheng T, Bias TK, Becker JB, et al. Prevalence and geographic variations of polypharmacy among West Virginia Medicaid beneficiaries. Ann Pharmacother. 2017;51(11):981–9. https://doi.org/10.1177/1060028017717017.
Hung CH, Tang TC, Wang CJ, Liu LK, Peng LN, Chen LK. Impact of living arrangements on clinical outcomes among older patients with dementia or cognitive impairment admitted to the geriatric evaluation and management unit in Taiwan. Geriatr Gerontol Int. 2017;17:44–9. https://doi.org/10.1111/ggi.13036.
McLean G, Hindle JV, Guthrie B, Mercer SW. Co-morbidity and polypharmacy in Parkinson’s disease: insights from a large Scottish primary care database. BMC Neurol. 2017;17(1):1–8. https://doi.org/10.1186/s12883-017-0904-4.
Mizokami F, Mizuno T, Mori T, Nagamatsu T, Endo H, Hirashita T, et al. Clinical medication review tool for polypharmacy: mapping approach for pharmacotherapeutic classifications. Geriatr Gerontol Int. 2017;17(11):2025–33. https://doi.org/10.1111/ggi.13014.
Park H-Y, Park J-W, Song HJ, Sohn HS, Kwon J-W. The association between polypharmacy and dementia: a nested case-control study based on a 12-year longitudinal cohort database in South Korea. PLoS One. 2017;12(1):e0169463. https://doi.org/10.1371/journal.pone.0169463.
Park H-Y, Park J-W, Sohn HS, Kwon J-W. Association of parkinsonism or parkinson disease with polypharmacy in the year preceding diagnosis: a nested case–control study in South Korea. Drug Saf. 2017;40(11):1109–18. https://doi.org/10.1007/s40264-017-0559-5.
Wawruch M, Zatko D, Wimmer G, Luha J, Wimmerova S, Kukumberg P, et al. Non-persistence with antiplatelet therapy in elderly patients after a transient ischemic attack. Aging Clin Exp Res. 2017;29(6):1121–7. https://doi.org/10.1007/s40520-017-0745-4.
Yeh CC, Lussier EC, Sun Y-T, Lan T-Y, Yu H-Y, Chang T-Y. Antiepileptic drug use among women from the Taiwanese registry of epilepsy and pregnancy: obstetric complications and fetal malformation outcomes. PLoS One. 2017;12(12):e0189497. https://doi.org/10.1371/journal.pone.0189497.
Yu N-W, Chen P-J, Tsai H-J, Huang C-W, Chiu Y-W, Tsay W-I, et al. Association of benzodiazepine and Z-drug use with the risk of hospitalisation for fall-related injuries among older people: a nationwide nested case–control study in Taiwan. BMC Geriatr. 2017;17(1):1–9. https://doi.org/10.1186/s12877-017-0530-4.
Asranna A, Jose M, Philip RM, Sarma PS, Thomas SV. Do anti-epileptic drug modifications after first trimester of pregnancy influence fetal malformation or cognitive outcome? Epilepsy Res. 2018;146:121–5. https://doi.org/10.1016/j.eplepsyres.2018.07.017.
Baek Y-H, Shin J-Y. Trends in polypharmacy over 12 years and changes in its social gradients in South Korea. PLoS One. 2018;13(9):e0204018. https://doi.org/10.1371/journal.pone.0204018.
Chiapella LC, Menna JM, Mamprin ME. Assessment of polypharmacy in elderly patients by using data from dispensed medications in community pharmacies: analysis of results by using different methods of estimation. Int J Clin Pharm. 2018;40(5):987–90. https://doi.org/10.1007/s11096-018-0663-3.
Cho H, Choi J, Kim Y-S, Son SJ, Lee KS, Hwang H-J, et al. Prevalence and predictors of potentially inappropriate prescribing of central nervous system and psychotropic drugs amongelderly patients: a national population study in Korea. Arch Gerontol Geriatr. 2018;74:1–8. https://doi.org/10.1016/j.archger.2017.08.013.
Faught E, Helmers S, Thurman D, Kim H, Kalilani L. Patient characteristics and treatment patterns in patients with newly diagnosed epilepsy: a US database analysis. Epilepsy Behav. 2018;85:37–44. https://doi.org/10.1016/j.yebeh.2018.05.019.
Fontanella CA, Hiance-Steelesmith DL, Guirgis H, Campo JV. Trends in and predictors of long-term antipsychotic polypharmacy use among Ohio Medicaid patients with schizophrenia, 2008–2014. Psychiatr Serv. 2018;69(9):1015–20. https://doi.org/10.1176/appi.ps.201800052.
Guilcher SJ, Hogan M-E, Calzavara A, Hitzig SL, Patel T, Packer T, et al. Prescription drug claims following a traumatic spinal cord injury for older adults: a retrospective population-based study in Ontario. Canada Spinal Cord. 2018;56(11):1059–68. https://doi.org/10.1038/s41393-018-0174-z.
Kadra G, Stewart R, Shetty H, MacCabe J, Chang CK, Taylor D, et al. Long-term antipsychotic polypharmacy prescribing in secondary mental health care and the risk of mortality. Acta Psychiatr Scand. 2018;138(2):123–32. https://doi.org/10.1111/acps.12906.
Kadra G, Stewart R, Shetty H, MacCabe JH, Chang C-K, Kesserwani J, et al. Antipsychotic polypharmacy prescribing and risk of hospital readmission. Psychopharmacology. 2018;235(1):281–9. https://doi.org/10.1007/s00213-017-4767-6.
McIsaac DI, Wong CA, Bryson GL, van Walraven C. Association of polypharmacy with survival, complications, and healthcare resource use after elective noncardiac surgery: a population-based cohort study. Anesthesiology. 2018;128(6):1140–50. https://doi.org/10.1097/ALN.0000000000002124.
Morin L, Johnell K, Laroche M-L, Fastbom J, Wastesson JW. The epidemiology of polypharmacy in older adults: register-based prospective cohort study. Clin Epidemiol. 2018;10:289–98. https://doi.org/10.2147/CLEP.S153458.
Subesinghe S, Rutherford AI, Byng-Maddick R, Leanne Hyrich K, Benjamin GJ. Recurrent serious infections in patients with rheumatoid arthritis—results from the British Society for Rheumatology biologics register. Rheumatology. 2018;57(4):651–5. https://doi.org/10.1093/rheumatology/kex469.
Wastesson JW, Cedazo Minguez A, Fastbom J, Maioli S, Johnell K. The composition of polypharmacy: a register-based study of swedes aged 75 years and older. PLoS One. 2018;13(3):e0194892. https://doi.org/10.1371/journal.pone.0194892.
Ivanova I, Elseviers M, Wettermark B, Schmidt Mende K, Vander Stichele R, Christiaens T. Electronic assessment of cardiovascular potentially inappropriate medications in anadministrative population database. Basic Clin Pharmacol Toxicol. 2019;124(1):62–73. https://doi.org/10.1111/bcpt.13095.
Thunander SL, Hedborg K. Association between prescribed antidepressants and other prescribeddrugs differ by gender: a nationwide register-based study in Sweden. Nord J Psychiatry. 2019;73(1):73–9. https://doi.org/10.1080/08039488.2018.1536766.
van den Akker M, Vaes B, Goderis G, Van Pottelbergh G, De Burghgraeve T, Henrard S. Trends in multimorbidity and polypharmacy in the Flemish-Belgian population between 2000 and 2015. PLoS One. 2019;14(2):e0212046. https://doi.org/10.1371/journal.pone.0212046.
Wastesson JW, Morin L, Laroche ML, Johnell K. How chronic is polypharmacy in old age? Alongitudinal nationwide cohort study. J Am Geriatr Soc. 2019;67(3):455–62. https://doi.org/10.1111/jgs.15717.
Leelakanok N, Holcombe AL, Lund BC, Gu X, Schweizer ML. Association between polypharmacy and death: a systematic review and meta-analysis. J Am Pharm Assoc. 2017;57(6):729–738. e710. https://doi.org/10.1016/j.japh.2017.06.002.
Jyrkkä J, Enlund H, Lavikainen P, Sulkava R, Hartikainen S. Association of polypharmacy with nutritional status, functional ability and cognitive capacity over a three-year period in an elderly population. Pharmacoepidemiol Drug Saf. 2011;20(5):514–22. https://doi.org/10.1002/pds.2116.
Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010. BMC Med. 2015;13(1):1–10. https://doi.org/10.1186/s12916-015-0322-7.
Lalic S, Sluggett JK, Ilomäki J, Wimmer BC, Tan EC, Robson L, et al. Polypharmacy and medication regimen complexity as risk factors for hospitalization among residents of long-term care facilities: a prospective cohort study. J Am Med Dir Assoc. 2016;17(11):1067. e1061–6. https://doi.org/10.1016/j.jamda.2016.08.019.
Fried TR, O'Leary J, Towle V, Goldstein MK, Trentalange M, Martin DK. Health outcomes associated with polypharmacy in community-dwelling older adults: a systematic review. J Am Geriatr Soc. 2014;62(12):2261–72. https://doi.org/10.1111/jgs.13153.
Johansson T, Abuzahra ME, Keller S, Mann E, Faller B, Sommerauer C, et al. Impact of strategies to reduce polypharmacy on clinically relevant endpoints: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(2):532–48. https://doi.org/10.1111/bcp.12959.
Hill-Taylor B, Walsh K, Stewart S, Hayden J, Byrne S, Sketris I. Effectiveness of the STOPP/START (screening tool of older Persons' potentially inappropriate prescriptions/screening tool to alert doctors to the right treatment) criteria: systematic review and meta-analysis of randomized controlled studies. J Clin Pharm Ther. 2016;41(2):158–69. https://doi.org/10.1111/jcpt.12372.
Kua C-H, Mak VS, Lee SWH. Health outcomes of deprescribing interventions among older residents in nursing homes: a systematic review and meta-analysis. J Am Med Dir Assoc. 2019;20(3):362–372. e311. https://doi.org/10.1016/j.jamda.2018.10.026.
Martyn-St James M, Faria R, Wong R, Scope A. Evidence for the impact of interventions and medicines reconciliation on problematic polypharmacy in the UK: a rapid review of systematic reviews. Br J Clin Pharmacol. 2021;87(1):42–75. https://doi.org/10.1111/bcp.14368.
Rankin A, Cadogan CA, Patterson SM, Kerse N, Cardwell CR, Bradley MC, et al. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev. 2018;5(12):e009235. https://doi.org/10.1002/14651858.CD008165.pub4.
Clyne B, Bradley MC, Hughes C, Fahey T, Lapane KL. Electronic prescribing and other forms of technology to reduce inappropriate medication use and polypharmacy in older people: a review of current evidence. Clin Geriatr Med. 2012;28(2):301–22. https://doi.org/10.1016/j.cger.2012.01.009.
Page AT, Clifford RM, Potter K, Schwartz D, Etherton-Beer CD. The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(3):583–623. https://doi.org/10.1111/bcp.12975.
The authors have no of funding to declare.
Ethics approval and consent to participate
Consent for publication
The authors declare they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Search Strategy using Medline Database.
Baseline Characteristics of Included Studies.
Descriptive Definitions and Measurement Indicators of Polypharmacy and Alternative Terms across Studies.
Prevalence of Polypharmacy Associated with Different Age Subgroups.
Prevalence of Polypharmacy Associated with Different Medication Thresholds.
Prevalence of Polypharmacy Associated with Settings of Study.
Prevalence of Polypharmacy Associated with Sex.
Prevalence of Polypharmacy Associated with Study Geographical Location.
Prevalence of Polypharmacy Associated with Different Study Designs.
Risk of Bias Summary in Included Studies (n = 106).
Funnel Plot of Prevalence of Polypharmacy in Included Studies.
About this article
Cite this article
Delara, M., Murray, L., Jafari, B. et al. Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis. BMC Geriatr 22, 601 (2022). https://doi.org/10.1186/s12877-022-03279-x
- Multiple medication prescribing
- Population-based study
- Administrative database