The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010

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Abstract

Background

The escalating use of prescribed drugs has increasingly raised concerns about polypharmacy. This study aims to examine changes in rates of polypharmacy and potentially serious drug-drug interactions in a stable geographical population between 1995 and 2010.

Methods

This is a repeated cross-sectional analysis of community-dispensed prescribing data for all 310,000 adults resident in the Tayside region of Scotland in 1995 and 2010. The number of drug classes dispensed and the number of potentially serious drug-drug interactions (DDIs) in the previous 84 days were calculated, and age-sex standardised rates in 1995 and 2010 compared. Patient characteristics associated with receipt of ≥10 drugs and with the presence of one or more DDIs were examined using multilevel logistic regression to account for clustering of patients within primary care practices.

Results

Between 1995 and 2010, the proportion of adults dispensed ≥5 drugs doubled to 20.8%, and the proportion dispensed ≥10 tripled to 5.8%. Receipt of ≥10 drugs was strongly associated with increasing age (20–29 years, 0.3%; ≥80 years, 24.0%; adjusted OR, 118.3; 95% CI, 99.5–140.7) but was also independently more common in people living in more deprived areas (adjusted OR most vs. least deprived quintile, 2.36; 95% CI, 2.22–2.51), and in people resident in a care home (adjusted OR, 2.88; 95% CI, 2.65–3.13). The proportion with potentially serious drug-drug interactions more than doubled to 13% of adults in 2010, and the number of drugs dispensed was the characteristic most strongly associated with this (10.9% if dispensed 2–4 drugs vs. 80.8% if dispensed ≥15 drugs; adjusted OR, 26.8; 95% CI 24.5–29.3).

Conclusions

Drug regimens are increasingly complex and potentially harmful, and people with polypharmacy need regular review and prescribing optimisation. Research is needed to better understand the impact of multiple interacting drugs as used in real-world practice and to evaluate the effect of medicine optimisation interventions on quality of life and mortality.

Electronic supplementary material

The online version of this article (doi:10.1186/s12916-015-0322-7) contains supplementary material, which is available to authorized users.

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Most cited references 22

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Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review.

Harriette Van Spall, Andrew Toren, Alex Kiss … (2007)

Selective eligibility criteria of randomized controlled trials (RCTs) are vital to trial feasibility and internal validity. However, the exclusion of certain patient populations may lead to impaired generalizability of results. To determine the nature and extent of exclusion criteria among RCTs published in major medical journals and the contribution of exclusion criteria to the representation of certain patient populations. The MEDLINE database was searched for RCTs published between 1994 and 2006 in certain general medical journals with a high impact factor. Of 4827 articles, 283 were selected using a series technique. Trial characteristics and the details regarding exclusions were extracted independently. All exclusion criteria were graded independently and in duplicate as either strongly justified, potentially justified, or poorly justified according to previously developed and pilot-tested guidelines. Common medical conditions formed the basis for exclusion in 81.3% of trials. Patients were excluded due to age in 72.1% of all trials (60.1% in pediatric populations and 38.5% in older adults). Individuals receiving commonly prescribed medications were excluded in 54.1% of trials. Conditions related to female sex were grounds for exclusion in 39.2% of trials. Of all exclusion criteria, only 47.2% were graded as strongly justified in the context of the specific RCT. Exclusion criteria were not reported in 12.0% of trials. Multivariable analyses revealed independent associations between the total number of exclusion criteria and drug intervention trials (risk ratio, 1.35; 95% confidence interval, 1.11-1.65; P = .003) and between the total number of exclusion criteria and multicenter trials (risk ratio, 1.26; 95% confidence interval, 1.06-1.52; P = .009). Industry-sponsored trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, and age. Drug intervention trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, female sex, and socioeconomic status. Among such trials, justification for exclusions related to concomitant medication use and comorbidities were more likely to be poorly justified. The RCTs published in major medical journals do not always clearly report exclusion criteria. Women, children, the elderly, and those with common medical conditions are frequently excluded from RCTs. Trials with multiple centers and those involving drug interventions are most likely to have extensive exclusions. Such exclusions may impair the generalizability of RCT results. These findings highlight a need for careful consideration and transparent reporting and justification of exclusion criteria in clinical trials.

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Adverse drug events in ambulatory care.

Tejal Gandhi, Saul N Weingart, Joshua Borus … (2003)

Adverse events related to drugs occur frequently among inpatients, and many of these events are preventable. However, few data are available on adverse drug events among outpatients. We conducted a study to determine the rates, types, severity, and preventability of such events among outpatients and to identify preventive strategies. We performed a prospective cohort study, including a survey of patients and a chart review, at four adult primary care practices in Boston (two hospital-based and two community-based), involving a total of 1202 outpatients who received at least one prescription during a four-week period. Prescriptions were computerized at two of the practices and handwritten at the other two. Of the 661 patients who responded to the survey (response rate, 55 percent), 162 had adverse drug events (25 percent; 95 percent confidence interval, 20 to 29 percent), with a total of 181 events (27 per 100 patients). Twenty-four of the events (13 percent) were serious, 51 (28 percent) were ameliorable, and 20 (11 percent) were preventable. Of the 51 ameliorable events, 32 (63 percent) were attributed to the physician's failure to respond to medication-related symptoms and 19 (37 percent) to the patient's failure to inform the physician of the symptoms. The medication classes most frequently involved in adverse drug events were selective serotonin-reuptake inhibitors (10 percent), beta-blockers (9 percent), angiotensin-converting-enzyme inhibitors (8 percent), and nonsteroidal antiinflammatory agents (8 percent). On multivariate analysis, only the number of medications taken was significantly associated with adverse events. Adverse events related to drugs are common in primary care, and many are preventable or ameliorable. Monitoring for and acting on symptoms are important. Improving communication between outpatients and providers may help prevent adverse events related to drugs. Copyright 2003 Massachusetts Medical Society

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Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity.

Lloyd D. Hughes, Marion McMurdo, Bruce Guthrie (2013)

currently one of the major challenges facing clinical guidelines is multimorbidity. Current guidelines are not designed to consider the cumulative impact of treatment recommendations on people with several conditions, nor to allow comparison of relative benefits or risks. This is despite the fact that multimorbidity is a common phenomenon. to examine the extent to which National Institute of Health and Clinical Excellence (NICE) guidelines address patient comorbidity, patient centred care and patient compliance to treatment recommendations. five NICE clinical guidelines were selected for review (type-2 diabetes mellitus, secondary prevention for people with myocardial infarction, osteoarthritis, chronic obstructive pulmonary disease and depression) as these conditions are common causes of comorbidity and the guidelines had all been produced since 2007. Two authors extracted information from each full guideline and noted the extent to which the guidelines accounted for patient comorbidity, patient centred care and patient compliance. The cumulative recommended treatment, follow-up and self-care regime for two hypothetical patients were then created to illustrate the potential cumulative impact of applying single disease recommendations to people with multimorbidity. comorbidity and patient adherence were inconsistently accounted for in the guidelines, ranging from extensive discussion to none at all. Patient centred care was discussed in generic terms across the guidelines with limited disease-specific recommendations for clinicians. Explicitly following guideline recommendations for our two hypothetical patients would lead to a considerable treatment burden, even when recommendations were followed for mild to moderate conditions. In addition, the follow-up and self-care regime was complex potentially presenting problems for patient compliance. clinical guidelines have played an important role in improving healthcare for people with long-term conditions. However, in people with multimorbidity current guideline recommendations rapidly cumulate to drive polypharmacy, without providing guidance on how best to prioritise recommendations for individuals in whom treatment burden will sometimes be overwhelming.

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Author and article information

Contributors

Bruce Guthrie: b.guthrie@dundee.ac.uk

Boikanyo Makubate: makubateb@biust.ac.bw

Virginia Hernandez-Santiago: v.z.hernandezsantiago@dundee.ac.uk

Tobias Dreischulte: t.dreischulte@dundee.ac.uk

Journal

Journal ID (nlm-ta): BMC Med

Journal ID (iso-abbrev): BMC Med

Title: BMC Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1741-7015

Publication date (Electronic): 7 April 2015

Publication date PMC-release: 7 April 2015

Publication date Collection: 2015

Volume: 13

Electronic Location Identifier: 74

Affiliations

[ ]Population Health Sciences Division, Medical Research Institute, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF UK

[ ]Department of Public Health, Faculty of Medicine, University of Botswana, Private Bag UB 0022, Gaborone, Botswana

[ ]NHS Tayside Medicines Governance Unit, Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF UK

Article

Publisher ID: 322

DOI: 10.1186/s12916-015-0322-7

PMC ID: 4417329

PubMed ID: 25889849

SO-VID: 9eefa692-f46b-428e-8825-c757933675d3

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 16 January 2015

Date accepted : 11 March 2015

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: drug interactions,family practice,physician,polypharmacy,prescribing patterns,primary care

Data availability:

ScienceOpen disciplines: Medicine

Keywords: drug interactions, family practice, physician, polypharmacy, prescribing patterns, primary care

The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010

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Drug Repurposing Research Collection

Most cited references 22

Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review.

Adverse drug events in ambulatory care.

Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity.

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