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The controversies surrounding polypharmacy in old age - where are we?
... The main challenge is to account for confounding by multiple indications (confounding by multimorbidity and frailty) [24], which means separating the potentially negative effect of polypharmacy from the effect of multiple diseases [15]. There is a need for translational research where large epidemiological data and pre-clinical models in concert help to inform about the underlying mechanisms and effects of pharmacotherapy in old age [25]. ...
... The great complexity of geriatric pharmacotherapy renders great need for precision medicine [25,31]. Clinicians need tools for improved prediction of expected clinical effects and risk of side effects in individual older patients [25,32]. ...
... The great complexity of geriatric pharmacotherapy renders great need for precision medicine [25,31]. Clinicians need tools for improved prediction of expected clinical effects and risk of side effects in individual older patients [25,32]. For a given patient, the challenge is to individualise treatment to minimise risks of drug treatment without denying older people valuable drug therapy. ...
With ageing of the population worldwide and discovery of new medications for prevention and management of age-related conditions, there is increasing use of medications by older adults. There are international efforts to increase the representativeness of participants in clinical trials to match the intended real-world users of the medications across a range of characteristics including age, multimorbidity, polypharmacy and frailty. Currently, much of the data on medication-related harm in older adults are from pharmacovigilance studies. New methods in pre-clinical models have allowed for measurement of exposures (such as chronic exposure, polypharmacy and deprescribing) and outcomes (such as health span functional measures and frailty) that are highly relevant to geriatric pharmacotherapy. Here we describe opportunities for design and implementation of pre-clinical models that can better predict drug effects in geriatric patients. This could improve the translation of new drugs from bench to bedside and improve outcomes of pharmacotherapy in older adults.
... Sebagian besar pasien geriatri mengalami beberapa penyakit sekaligus sehingga terapi yang diperoleh termasuk dalam kategori polifarmasi yaitu penggunaan lima obat atau lebih (Johnell, 2018). Polifarmasi sering dikaitkan dengan risiko terjadinya kejadian yang merugikan seperti interaksi obat, reaksi efek samping, duplikasi, over dosis, jumlah hospitalisasi, biaya dan bahkan kematian. ...
"SOAP", yang merupakan singkatan dari subjektif, objektif, assesmen, dan plan, adalah alat yang digunakan untuk mendokumentasikan catatan perawatan pasien secara terstruktur dan terorganisir. Metode pencatatan ini dikembangkan pada tahun 1960 oleh Dr. Lawrence Weed di Universitas Vermont sebagai bagian dari rekam medis yang berorientasi pada masalah. Catatan terapeutik terstruktur yang mengoptimalkan pengobatan, membantu akuntabilitas, dan mendukung pengambilan keputusan klinis. Profesional kesehatan menggunakannya untuk memberikan rekomendasi farmakoterapi dan melacak prognosis pasien (Sudarsan et al., 2021).
SOAP merupakan dokumentasi yang rapi dan teratur tentang pasien dan dapat dijadikan salah satu preferensi dalam Evidence Based Medicine (EBM). Evidence Based Medicine (EBM) didefinisikan sebagai penggunaan bukti terbaik dan terkini secara teliti, eksplisit dan bijaksana dalam membuat keputusan mengenai perawatan pasien secara individu. EBM merupakan gabungan penilaian dan pengalaman klinis, bukti ilmiah terbaik yang tersedia, dan preferensi pasien untuk meningkatkan pengambilan keputusan medis. Penyedia layanan kesehatan menghadapi tantangan dalam meningkatkan efisiensi dan efektivitas, termasuk apoteker. Mereka harus terus memperbarui pengetahuan dan keterampilan, dengan mengandalkan bukti, meskipun sumber daya yang relevan berlimpah. Praktisi farmasi harus memiliki keterampilan yang memadai untuk mengevaluasi catatan pasien dan juga literatur (Farha et al., 2014).
... In which case, the deprescribing of these medications may not be warranted. The variety of medication combinations prescribed to the 95-year-old participants (Fig. 1) further illustrates that 'one size does not fit all' when it comes to polypharmacy [2,30]. ...
Background
Previous research has examined prescribing amongst 85-year-olds in English primary care, but less is known about prescribing amongst 95-year-olds in spite of population ageing.
Aim
We describe the most commonly prescribed medicines in a cohort of 95-year-olds, using 10-year follow-up data from the Newcastle 85+ Study (n = 90).
Method
A total of 1040 participants were recruited to the Newcastle 85+ Study through general practices at 85-years of age, and 90 surviving participants were re-contacted and assessed at 95-years of age. Prescribed medications from general practice medical records were examined through cross-tabulations and classified as preventative or for symptom control based on their customary usage.
Results
Preventative medications with unclear evidence of benefit such as statins (36.7%), aspirin (21.1%) and bisphosphonates (18.9%) were frequently prescribed.
Conclusions
Future research in a larger clinical dataset could investigate this preliminary trend, which suggests that benefit/risk information for preventive medication, and evidence for deprescribing, is needed in the very old.
... AGING Nevertheless, there is little experimental data about the potentially negative effects caused by polypharmacy and on the mechanisms behind these effects [11]. Drug safety studies often exclude older patients and are limited to monotherapies. ...
The potential harmful effects of polypharmacy (concurrent use of 5 or more drugs) are difficult to investigate in an experimental design in humans. Moreover, there is a lack of knowledge on sex-specific differences on the outcomes of multiple-drug use. The present study aims to investigate the effects of an eight-week exposure to a regimen of five different medications (metoprolol, paracetamol, aspirin, simvastatin and citalopram) in young adult female mice. Polypharmacy-treated animals showed significant impairment in object recognition and fear associated contextual memory, together with a significant reduction of certain hippocampal proteins involved in pathways necessary for the consolidation of these types of memories, compared to animals with standard diet. The impairments in explorative behavior and spatial memory that we reported previously in young adult male mice administered the same polypharmacy regimen were not observed in females in the current study. Therefore, the same combination of medications induced different negative outcomes in young adult male and female mice, causing a significant deficit in non-spatial memory in female animals. Overall, this study strongly supports the importance of considering sex-specific differences in designing safer and targeted multiple-drug therapies.
... The number of prescribed potentially inappropriate medications was the same with a small tendency to increase during the two follow-up years, which according to the literature could be associated with an increase in the medication-medication and medication-comorbidity interactions (37). Additionally, in our study, the number of comorbidities during follow-up increased suggesting the need for more medications as evidenced at the two-year mark. ...
Introduction:
Potentially inappropriate medication is associated with adverse health and functional outcomes, as well as increased health care costs.
Objective:
To estimate the prevalence and types of potentially inappropriate medication according to the Beers criteria in community-dwelling older persons and to identify the major clinical and functional consequences of potentially inappropriate medication during two years of following.
Materials and methods:
We conducted a longitudinal, descriptive, and observational study that included 400 65-year or older community-dwelling people (48% women) selected by simple random sampling in 2012. In 2014, 372 people were re-evaluated and classified into two groups based on the presence or absence of potentially inappropriate medication through the follow-up period.
Results:
In total, 31% had polypharmacy (5-9 medications) and 1,8% had excessive polypharmacy (10 or more medications). The mean of the number of medications was higher in the potentially inappropriate medication group (3 vs. 5.78; p<0.001) and 21.9% still had the potentially inappropriate medication status during the follow-up; of them, 75% had one potentially inappropriate medication and 23% two. The presence of potentially inappropriate medication was more frequent among frail and depressed male individuals with a bad health self-assessment and comorbidities, especially diabetes mellitus and chronic obstructive pulmonary disease. In the group with sustained potentially inappropriate medication, we found a worsening health self-assessment, increased frailty, a higher incidence of recurrent falls and prevalence of depression, as well as a higher hospital admission rate, ambulatory medical consultation, and more prescribed medications. We did not find an impact on functional capacity.
Conclusions:
We validated the negative effects of potentially inappropriate medication in the long run for the health of older people and, therefore, potentially inappropriate medications should be monitored in primary care services to avoid greater risks.
... The term polypharmacy is imprecise and its definition is yet subject to an ongoing debate [89]. Our findings regarding the definition of polypharmacy are in line with several previous studies [7,11,14,90]. ...
Background
The number of older adults has been constantly growing around the globe. Consequently, multimorbidity and related polypharmacy have become an increasing problem. In the absence of an accepted agreement on the definition of polypharmacy, data on its prevalence in various studies are not easily comparable. Besides, the evidence on the potential adverse clinical outcomes related to polypharmacy is limited though polypharmacy has been linked to numerous adverse clinical outcomes. This narrative review aims to find and summarize recent publications on definitions, epidemiology and clinical consequences of polypharmacy.
Methods
The MEDLINE database was used to identify recent publications on the definition, prevalence and clinical consequences of polypharmacy using their respective common terms and their variations. Systematic reviews and original studies published between 2015 and 2020 were included.
Results
One hundred and forty-three definitions of polypharmacy and associated terms were found. Most of them are numerical definitions. Its prevalence ranges from 4% among community-dwelling older people to over 96.5% in hospitalized patients. In addition, numerous adverse clinical outcomes were associated with polypharmacy.
Conclusion
The term polypharmacy is imprecise, and its definition is yet subject to an ongoing debate. The clinically oriented definitions of polypharmacy found in this review such as appropriate or necessary polypharmacy are more useful and relevant. Regardless of the definition, polypharmacy is highly prevalent in older adults, particularly in nursing home residents and hospitalized patients. Approaches to increase the appropriateness of polypharmacy can improve clinical outcomes in older adults.
... Finally, polypharmacy combinations were diverse, reflecting the heterogeneity of multimorbidity [37] and propensity for other determinants of medication use,-such as renal function, frailty and medication tolerability -, to vary from person to person in very late life. Indeed, 'one size does not fit all' when it comes to polypharmacy [67]. ...
Background
Polypharmacy is potentially harmful and under-researched amongst the fastest growing subpopulation, the very old (aged ≥85). We aimed to characterise polypharmacy using data from the Newcastle 85+ Study—a prospective cohort of people born in 1921 who turned 85 in 2006 (n = 845).
Methods
The prevalence of polypharmacy at baseline (mean age 85.5) was examined using cut-points of 0, 1, 2–4, 5–9 and ≥10 medicines—so-called ‘no polypharmacy’, ‘monotherapy’, ‘minor polypharmacy’, ‘polypharmacy’ and ‘hyperpolypharmacy.’ Cross-tabulations and upset plots identified the most frequently prescribed medicines and medication combinations within these categories. Mixed-effects models assessed whether gender and socioeconomic position were associated with prescribing changes over time (mean age 85.5–90.5). Participant characteristics were examined through descriptive statistics.
Results
Complex multimorbidity (44.4%, 344/775) was widespread but hyperpolypharmacy was not (16.0%, 135/845). The median medication count was six (interquartile range 4–8). Preventative medicines were common to all polypharmacy categories, and prescribing regimens were diverse. Nitrates and oral anticoagulants were more frequently prescribed for men, whereas bisphosphonates, non-opioid analgesics and antidepressants were more common in women. Cardiovascular medicines, including loop diuretics, tended to be more frequently prescribed for socioeconomically disadvantaged people (<25th centile Index of Multiple Deprivation (IMD)), despite no difference in the prevalence of cardiovascular disease (p = 0.56) and diabetes (p = 0.92) by IMD.
Conclusion
Considering their complex medical conditions, prescribing is relatively conservative amongst 85-year-olds living in North East England. Prescribing shows significant gender and selected socioeconomic differences. More support for managing preventative medicines, of uncertain benefit, might be helpful in this population.
... Taken together these aspects underline the importance of investigating the potentially harmful effects from concomitant administration of different drugs, which so far have been poorly explored. The approach and outcomes of our study can be applied in old mice to mimic the real-world setting where older adults frequently use multiple drugs [60]. The results from the present study can be valuable to interpret future results on aged mice, although the experimental design used here would need optimization due to possible age-related limitations (e.g. ...
A major challenge in the health care system is the lack of knowledge about the possible harmful effects of multiple drug treatments in old age. The present study aims to characterize a mouse model of polypharmacy, in order to investigate whether long-term exposure to multiple drugs could lead to adverse outcomes. To this purpose we selected five drugs from the ten most commonly used by older adults in Sweden (metoprolol, paracetamol, aspirin, simvastatin and citalopram). Five-month-old wild type male mice were fed for eight weeks with control or polypharmacy diet. We report for the first time that young adult polypharmacy-treated mice showed a significant decrease in exploration and spatial working memory compared to the control group. This memory impairment was further supported by a significant reduction of synaptic proteins in the hippocampus of treated mice. These novel results suggest that already at young adult age, use of polypharmacy affects explorative behavior and synaptic functions. This study underlines the importance of investigating the potentially negative outcomes from concomitant administration of different drugs, which have been poorly explored until now. The mouse model proposed here has translatable findings and can be applied as a useful tool for future studies on polypharmacy.
... The risk of a prescribing cascade increases both with interactions (drug-drug) and contraindications (drug-disease) [10,11]. Nonetheless, polypharmacy is not wrong, per se, as long as the complete medication list is reviewed, and the risk/benefit ratio is considered for the individual patient, which is called appropriate polypharmacy [1,12]. ...
Background:
With age, the number of chronic conditions increases along with the use of medications. For several years, polypharmacy has been found to be on the increase in western societies. Polypharmacy is associated with an increased risk of adverse drug events (ADE). Medications called potentially inappropriate medications (PIM) have also been found to increase the risk of ADEs in an older population. In this study, which we conducted during a national information campaign to reduce PIM, we analysed the prevalence of PIM in an older adult population and in different strata of the variables age, gender, number of chronic conditions and polypharmacy and how that prevalence changed over time.
Methods:
This is a registry-based repeated cross-sectional study including two cohorts. Individuals aged 75 or older listed at a primary care centre in Blekinge on the 31st March 2011 (cohort 1, 15,361 individuals) or on the 31st December 2013 (cohort 2, 15,945 individuals) were included in the respective cohorts. Using a chi2 test, the two cohorts were compared on the variables age, gender, number of chronic conditions and polypharmacy. Use of five or more medications at the same time was the definition for polypharmacy.
Results:
Use of PIM decreased from 10.60 to 7.04% (p-value < 0.001) between 2011 and 2013, while prevalence of five to seven chronic conditions increased from 20.55 to 23.66% (p-value < 0.001). Use of PIM decreased in all strata of the variables age, gender number of chronic conditions and polypharmacy. Except for age 80-84 and males, where it increased, prevalence of polypharmacy was stable in all strata of the variables.
Conclusions:
Use of potentially inappropriate medications had decreased in all variables between 2011 and 2013; this shows the possibility to reduce PIM with a focused effort. Polypharmacy does not increase significantly compared to the rest of the population.
... Second, PP (our dependent variable) was defined based on a self-reported number of prescribed medications. This approach is prone to recall bias [84]. Future research should collect medication data from pharmacy charts or insurance claims, rather than simply relying on patients' self-reports. ...
Background: Very few studies with nationally representative samples have investigated the combined effects of race/ethnicity and socioeconomic position (SEP) on polypharmacy (PP) among older Americans. For instance, we do not know if prevalence of PP differs between African Americans (AA) and white older adults, whether this difference is due to a racial gap in SEP, or whether racial and ethnic differences exist in the effects of SEP indicators on PP. Aims: We investigated joint effects of race/ethnicity and SEP on PP in a national household sample of American older adults. Methods: The first wave of the University of Michigan National Poll on Healthy Aging included a total of 906 older adults who were 65 years or older (80 AA and 826 white). Race/ethnicity, SEP (income, education attainment, marital status, and employment), age, gender, and PP (using 5+ medications) were measured. Logistic regression was applied for data analysis. Results: Race/ethnicity, age, marital status, and employment did not correlate with PP; however, female gender, low education attainment, and low income were associated with higher odds of PP among participants. Race/ethnicity interacted with low income on odds of PP, suggesting that low income might be more strongly associated with PP in AA than white older adults. Conclusions: While SEP indicators influence the risk of PP, such effects may not be identical across diverse racial and ethnic groups. That is, race/ethnicity and SEP have combined/interdependent rather than separate/independent effects on PP. Low-income AA older adults particularly need to be evaluated for PP. Given that race and SEP have intertwined effects on PP, racially and ethnically tailored interventions that address PP among low-income AA older adults may be superior to universal interventions and programs that ignore the specific needs of diverse populations. The results are preliminary and require replication in larger sample sizes, with PP measured directly without relying on individuals’ self-reports, and with joint data collected on chronic disease.
Medication therapy in older adults is complicated by the frequent presence of comorbidity that requires coadministration of multiple therapeutic agents. This need for polypharmacy increases the likelihood of potentially harmful drug interactions and adverse events. In addition, there are important pharmacokinetic and pharmacodynamic changes in older adults that further complicate the therapy of these individuals. Among the former are reduced renal function and CYP-mediated drug metabolism. Older patients are also more sensitive to drugs that act on the central nervous and cardiovascular systems and indiscriminate use of agents that act on these systems leads to an increase in falls and serious injury. This chapter highlights that need for more research and clinical guidance in this area.
Polymedication is associated with a higher incidence of negative health indicators including falls, morbidity and mortality. Despite efforts, the solution to this problem is still unsatisfactory. The two main causes of polymedication are population aging and polymorbidity and, on the other hand, the development of the pharmaceutical industry and the availability of a wide range of medicines. The authors discuss the main shortcomings in the investigation of this issue, such as inconsistent terminology used, methodological shortcomings in data acquisition, lack of recommended guidelines for the polymorbid patients treatment, etc. They discuss whether polymedication is the cause or marker of increased falls, frailty and mortality. In the end they critically evaluate possible solution of polymedication in future - personalised medicine.
Objectives
To estimate the prevalence of polypharmacy (≥5 drugs) among adults and to analyze related factors.
Methods
Cross-sectional study with 1,159 interviewees distributed across 104 cities and 253 primary healthcare services delivered through the Brazilian Unified Health System. Polypharmacy-related factors were identified using logistic regression model.
Results
949 (81.8%) interviewees were using at least one medication and were included in this analysis. The prevalence of polypharmacy among them was 13.7% (95%CI:11.7–16.0%) in the general population and 33.3%(95%CI:26.1–41.4%) in older adults(≥65 years). Polypharmacy was positively associated with age (45 to 64 years, OR=2.02; 95%CI:1.03–3.94; ≥65 years, OR=4.17; 95%CI:1.92–9.17) and the following chronic diseases: stroke (OR=4.20; 95%CI:1.53–11.55); diabetes mellitus (OR=4.03; 95%CI:2.43–6.68); heart disease (OR=3.18; 95%CI:1.92–5.29); depression (OR=2.85; 95%CI:1.80–4.53); hypertension (OR=2.13; 95%CI:1.17–3.86); and dyslipidemia (OR=1.73; 95%CI:1.07–2.80).
Conclusion
This study revealed that polypharmacy is a real concern in primary health care and affects older and middle-aged adults alike. Groups of patients that are more likely to experience polypharmacy were identified. Our findings emphasize the relevance of an appropriate approach to polypharmacy driven by aging and multimorbidity.
Objective
Polypharmacy is the concomitant use of several drugs by a single person, and it increases the risk of adverse drug-related events in older adults. Little is known about the epidemiology of polypharmacy at the population level. We aimed to measure the prevalence and incidence of polypharmacy and to investigate the associated factors.
Methods
A prospective cohort study was conducted using register data with national coverage in Sweden. A total of 1,742,336 individuals aged ≥65 years at baseline (November 1, 2010) were included and followed until death or the end of the study (December 20, 2013).
Results
On average, individuals were exposed to 4.6 (SD =4.0) drugs at baseline. The prevalence of polypharmacy (5+ drugs) was 44.0%, and the prevalence of excessive polypharmacy (10+ drugs) was 11.7%. The incidence rate of polypharmacy among individuals without polypharmacy at baseline was 19.9 per 100 person-years, ranging from 16.8% in individuals aged 65–74 years to 33.2% in those aged ≥95 years (adjusted hazard ratio [HR] =1.49, 95% confidence interval [CI] 1.42–1.56). The incidence rate of excessive polypharmacy was 8.0 per 100 person-years. Older adults using multi-dose dispensing were at significantly higher risk of developing incident polypharmacy compared with those receiving ordinary prescriptions (HR =1.51, 95% CI 1.47–1.55). When adjusting for confounders, living in nursing home was found to be associated with lower risks of incident polypharmacy and incident excessive polypharmacy (HR =0.79 and HR =0.86, p<0.001, respectively).
Conclusion
The prevalence and incidence of polypharmacy are high among older adults in Sweden. Interventions aimed at reducing the prevalence of polypharmacy should also target potential incident polypharmacy users as they are the ones who fuel future polypharmacy.
Background
Multimorbidity and the associated use of multiple medicines (polypharmacy), is common in the older population. Despite this, there is no consensus definition for polypharmacy. A systematic review was conducted to identify and summarise polypharmacy definitions in existing literature. Methods
The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid), EMBASE and Cochrane were systematically searched, as well as grey literature, to identify articles which defined the term polypharmacy (without any limits on the types of definitions) and were in English, published between 1st January 2000 and 30th May 2016. Definitions were categorised as i. numerical only (using the number of medications to define polypharmacy), ii. numerical with an associated duration of therapy or healthcare setting (such as during hospital stay) or iii. Descriptive (using a brief description to define polypharmacy). ResultsA total of 1156 articles were identified and 110 articles met the inclusion criteria. Articles not only defined polypharmacy but associated terms such as minor and major polypharmacy. As a result, a total of 138 definitions of polypharmacy and associated terms were obtained. There were 111 numerical only definitions (80.4% of all definitions), 15 numerical definitions which incorporated a duration of therapy or healthcare setting (10.9%) and 12 descriptive definitions (8.7%). The most commonly reported definition of polypharmacy was the numerical definition of five or more medications daily (n = 51, 46.4% of articles), with definitions ranging from two or more to 11 or more medicines. Only 6.4% of articles classified the distinction between appropriate and inappropriate polypharmacy, using descriptive definitions to make this distinction. Conclusions
Polypharmacy definitions were variable. Numerical definitions of polypharmacy did not account for specific comorbidities present and make it difficult to assess safety and appropriateness of therapy in the clinical setting.
Importance
As older adults living in nursing homes are at a high risk of adverse drug-related events, medications with a poor benefit/risk ratio or with a safer alternative should be avoided.
Objectives
To systematically evaluate the prevalence of potentially inappropriate medication use in nursing home residents.
Evidence review
We searched in PubMed and EMBASE databases (1990–2015) for studies reporting the prevalence of potentially inappropriate medication use in people ≥60 years of age living in nursing homes. The risk of bias was assessed with an adapted version of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.
Findings
A total of 91 articles were assessed for eligibility, and 48 met our inclusion criteria. These articles reported the findings from 43 distinct studies, of which 26 presented point prevalence estimates of potentially inappropriate medication use (227,534 nursing home residents). The overall weighted point prevalence of potentially inappropriate medication use in nursing homes was 43.2% [95% confidence interval (CI) 37.3%–49.1%], increasing from 30.3% in studies conducted during 1990–1999 to 49.8% in studies conducted after 2005 (P < .001). Point prevalence estimates reported in European countries were found to be higher (49.0%, 95% CI 42.5–55.5) than those reported in North America (26.8%, 95% CI 16.5–37.1) or in other countries (29.8%, 95% CI 19.3–40.3). In addition, 18 studies accounting for 326,562 nursing home residents presented 20 distinct period prevalence estimates ranging from 2.3% to 50.3%. The total number of prescribed medications was consistently reported as the main driving factor for potentially inappropriate medications use.
Conclusions and relevance
This systematic review shows that almost one-half of nursing home residents are exposed to potentially inappropriate medications and suggests an increase prevalence over time. Effective interventions to optimize drug prescribing in nursing home facilities are, therefore, needed.
Pharmacogenomic (PGx) testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study. PGx testing identified major genetic polymorphisms in the first two cases. The first case was identified as “CYP3A4/CYP3A5 poor metabolizer”, which affected metabolism of eleven prescribed drugs. The second case had “CYP2D6 rapid metabolizer” status affecting three prescribed medications, two of which were key drugs for managing this patient’s chronic conditions. Both these patients also had VKORC1 allele *A, resulting in higher sensitivity to warfarin. All cases demonstrated a significant number of potential drug–drug interactions. Both patients with significant drug–gene interactions had a history of frequent hospitalizations (six and 23, respectively), whereas the person without impaired cytochrome P450 enzyme activity had only two acute episodes in the last 5 years, although he was older and had multiple comorbidities. Since all patients received guideline-concordant therapy from the same providers and were adherent to their drug regimen, we hypothesized that genetic polymorphism may represent an additional risk factor for higher hospitalization rates in older adults with polypharmacy. However, evidence to support or reject this hypothesis is yet to be established. Studies evaluating clinical impact of PGx testing in older adults with polypharmacy are warranted. For practical implementation of pharmacogenomics in routine clinical care, besides providing convincing evidence of its clinical effectiveness, multiple barriers must be addressed. Introduction of intelligent clinical decision support in electronic medical record systems is required to address complexities of simultaneous drug–gene and drug–drug interactions in older adults with polypharmacy. Physician training, clear clinical pathways, evidence-based guidelines, and patient education materials are necessary for unlocking full potential of pharmacogenomics into routine clinical care of older adults.
Inappropriate drug use is an important health problem in elderly persons. Beginning with the Beers' criteria in the early 1990s, explicit criteria have been extensively used to measure and improve quality of drug use in older people. This article describes the Swedish indicators for quality of drug therapy in the elderly, introduced in 2004 and updated in 2010. These indicators were designed to be applied to people aged 75 years and over, regardless of residence and other characteristics. The indicators are divided into drug specific, covering choice, indication and dosage of drugs, polypharmacy, drug-drug interactions (DDIs), drug use in decreased renal function and in some symptoms; and diagnosis specific, covering the rational, irrational and hazardous drug use in common disorders in elderly people. During the 10 years since introduction, the Swedish indicators have several applications. They form the basis for recommendations for drug therapy in older people, are implemented in prescribing supports and drug utilisation reviews, are used in national benchmarking of the quality of Swedish healthcare and have contributed to initiatives from pensioner organisations. The indicators have also been used in several pharmacoepidemiological studies. Since 2005, there have been signs of improvement of the quality of drug prescribing to elderly persons in Sweden. For example, the prescribing of drugs that should be avoided in older persons decreased by 36 % between 2006 and 2012 in persons aged 80 years and older. Similarly, drug combinations that may cause DDIs decreased by 26 % and antipsychotics by 41 %. The indicators have likely contributed to this.
Very few treatments tested in preclinical studies make their way into clinical trials—of 5000 compounds tested in animals, approximately 5 will show enough promise in human trials for a company to file an Investigational New Drug Application with the US Food and Drug Administration.
Background:
This study analyzes the prevalence and patterns of coexisting chronic conditions in older adults.
Design:
Cross-sectional.
Participant and setting:
A sample of 3363 people ≥60years living in Stockholm were examined from March 2001 through August 2004.
Measurements:
Chronic conditions were measured with: 1) multimorbidity (≥2 concurrent chronic diseases); 2) the Cumulative Illness Rating Scale, 3) polypharmacy (≥5 prescribed drugs), and 4) complex health problems (chronic diseases and/or symptoms along with cognitive and/or functional limitations).
Results:
A total of 55.6% of 60-74year olds and 13.4% of those ≥85years did not have chronic conditions according to the four indicators. Multimorbidity and polypharmacy were the most prevalent indicators: 38% aged 60-74 and 76% aged ≥85 had multimorbidity; 24.3% aged 60-74 and 59% aged ≥85 had polypharmacy. Prevalence of chronic conditions as indicated by the comorbidity index and complex health problems ranged from 16.5% and 1.5% in the 60-74year olds to 38% and 36% in the 85+ year olds, respectively. Prevalence of participants with 4 indicators was low, varying from 1.6% in those aged 60-74 to 14.9% in those aged ≥85years. Older age was associated with higher odds of each of the 4 indicators; being a woman, with all indicators but multimorbidity; and lower educational level, only with complex health problems.
Conclusions:
Prevalence of coexisting chronic conditions varies greatly by health indicator used. Variation increases when age, sex, and educational level are taken into account. These findings underscore the need of different indicators to capture health complexity in older adults.
We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n = 10) and old (n = 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2±13 counts, polypharmacy 32±7 counts, p < .05) and front paw wire holding impulse (control -2.45±1.02 N s, polypharmacy +1.99±1.19 N s, p < .05), loss of improvement in rotarod latency (control -59±11 s, polypharmacy -1.7±17 s, p < .05), and lowered blood pressure (control -0.2±3 mmHg, polypharmacy 11±4 mmHg, p < .05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice.
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Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.
Introduction:
The worldwide population is aging, and several age-associated physiological and pathophysiological changes can affect drug disposition. This is particularly important in view of the extensive medication prescribing and exposure in older adults.
Areas covered:
Using a framework of the four primary pharmacokinetic processes (Absorption, Distribution, Metabolism and Elimination), this review discusses the current evidence of the pharmacokinetic changes that occur with aging, particularly 'healthy aging,' focusing on developments in this field over the last 10 years.
Expert opinion:
A substantial amount of work has been conducted to address whether advancing age significantly affects drug disposition in humans. Despite significant advances in the field, particularly regarding drug metabolism and elimination, a number of issues remain unsolved. In particular, lack of inclusion of older adults with multimorbidity and those aged > 80 and minimal evidence in relation to new drugs limits the applicability of findings to current clinical practice.
To summarize evidence regarding the health outcomes associated with polypharmacy, defined as number of prescribed medications, in older community-dwelling persons.
Systematic review of MEDLINE (OvidSP 1946 to May, Week 3, 2014).
Community.
Observational studies examining health outcomes according to number of prescription medications taken.
Association between number of medications and health outcomes. Because of the importance of comorbidity as a potential confounder of the relationship between polypharmacy and health outcomes, articles were assessed regarding the quality of their adjustment for confounding.
Of the 50 studies identified, the majority that were rated good in terms of their adjustment for comorbidity demonstrated relationships between polypharmacy and a range of outcomes, including falls, fall outcomes, fall risk factors, adverse drug events, hospitalization, mortality, and measures of function and cognition. However, a number of these studies failed to demonstrate associations, as did a substantial proportion of studies rated fair or poor.
Data are mixed regarding the relationship between polypharmacy, considered in terms of number of medications, and adverse outcomes in community-dwelling older persons. Because of the challenge of confounding, randomized controlled trials of medication discontinuation may provide more-definitive evidence regarding this relationship than observational studies can provide.
© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
The exclusion of older adults, particularly those with complex and multiple chronic conditions, from randomized clinical trials (RCTs) has been well chronicled.1,2 Less well studied is how the preventive benefits seen in participants in RCTs translate to older individuals with multiple chronic health problems.Helping to fill this gap, O’Hare and coauthors3 investigate whether the benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in preventing progression to end-stage renal disease (ESRD) that are seen in younger populations would be similar for older adults. Using a simulation design, the authors provide evidence that the same relative benefit of ACEIs and ARBs seen in participants in RCTs do not provide the same absolute benefit in terms of less ESRD in older adults; this finding is important because the results from the participants in the RCTs inform current guidelines. For most of the older veterans in their study, more than 100 persons would need to be treated to prevent 1 case of ESRD. For many subgroups, the number needed to treat was greater than 1000, a sharp contrast to the range of 9 to 25 reported in the 4 trials highlighted in the article. These findings leave one wondering whether the poor translation of the effectiveness of ACEIs and ARBs from younger to older individuals is an isolated situation or whether we are unwittingly subjecting older adults to a wide array of preventive treatments that have no or marginal benefit or even impart unintended harm. The study by O’Hare et al supports the need to look at this question more systematically and calls into question the prevailing practice of assuming that results extrapolate from young to old and from healthier to sicker populations.
Prevalence of potentially inappropriate medication use in older adults living in nursing homes: a systematic review
- L Morin
- Laroche
- Ml
- G Texier