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Mirko Petrovic, Denis O’Mahony, Antonio Cherubini, Inappropriate prescribing: hazards and solutions, Age and Ageing, Volume 51, Issue 2, February 2022, afab269, https://doi.org/10.1093/ageing/afab269
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Abstract
With population ageing, the number of older people is growing, which results in increasing number of people with multimorbidity and related polypharmacy. Polypharmacy in its turn leads to drug-related problems (DRPs) and potentially inappropriate prescribing (IP) in older people. In this commentary, susceptibility of older people to DRPs due to changes in pharmacokinetics and pharmacodynamics, plurality of prescribing physicians, inadequate consideration of patients’ characteristics, polypharmacy and its consequences such as prescribing cascades, drug interactions and potentially IP have been discussed respectively. Consecutively, identifying DRPs and optimizing of IP, including drug reconciliation, application of criteria for identifying and preventing IP, implementation of computer-based prescribing systems, and comprehensive geriatric assessment and management have been elaborated as well. One of the main challenges regarding appropriate and tailored prescribing in older people is to evaluate whether the expected benefits of pharmacotherapy are bigger than the risks in a population with multimorbidity, decreased tolerance to vulnerability and limited life expectancy. Comprehensive geriatric assessment enables informed prescribing decisions in the context of such variables. A challenge for future research is how to integrate important clinical information obtained by existing methods into a comprehensive and wide-reaching approach targeting all potential factors involved in causing DRPs. Good prescribing in late life accommodates the needs of older patients with multimorbidity. Individualized, interactive, multidisciplinary, and multifaceted approach to geriatric pharmacotherapy should be promoted and encouraged. How to optimize pharmacological prescription in complex older patients is a major legacy of geriatrics to contemporary medicine/medical practice.
Key Points
Good prescribing in late life accommodates the needs of older patients with multimorbidity
Individualized, interactive, multidisciplinary and multifaceted approach to geriatric pharmacotherapy should be promoted
Optimizing pharmacotherapy in complex older patients is a major legacy of geriatrics to contemporary medical practice
With population ageing, there will be an increasing number of older people with multimorbidity. Multimorbidity generates polypharmacy, the most consistent predictor of drug-related problems (DRPs) and inappropriate prescribing (IP) in older people [1].
Polypharmacy
Usually, the definition of polypharmacy is based on the number of drugs, although this has been criticized as not being clinically relevant, since it does not take into account the appropriateness of medication use [2]. A threshold of ≥5 daily drugs has been shown to be useful in identifying patients who could benefit from an assessment of potentially inappropriate polypharmacy [3]. Polypharmacy is becoming more common and the prevalence varies depending on the setting and population studied. Up to 40% of people aged ≥65 years who live at home use ≥5 daily medicines on average [4]. CNS drug polypharmacy is particularly prevalent and in recent years has increased to over 35% in people aged ≥75 years [5]. Polypharmacy is more prevalent in frail older people with multimorbidity compared to robust older adults. Among older men still living at home, polypharmacy was reported in 65% of frail men compared to 27% in robust men [6]. Polypharmacy is a problematic issue also in nursing home residents [7].
Polypharmacy is associated with a higher risk of DRPs and negative patient-related outcomes. Moreover, polypharmacy increases the risk of adverse outcomes including drug–drug interactions, drug-disease interactions, decreased medication adherence, IP, adverse drug reactions and side-effects, higher hospitalization rate, falls, functional decline and increased mortality [8]. Not surprisingly, polypharmacy correlates closely with frailty in older people [9, 10]. Among community-dwelling older men, polypharmacy is associated with the transition from pre-frail to frail status and death [11]. There is a need for more research to develop a definition of polypharmacy that is more clinically meaningful and useful.
Susceptibility of older people to drug-related problems
DRPs are defined as medication-related events or conditions that interfere with the patient’s experience of the optimal outcome of medical care [12]. Several factors are responsible for the high incidence of DRPs in older people compared to younger and middle-aged people [9, 13, 14]. Firstly, multimorbidity and polypharmacy increase the risk of both drug–drug and drug–disease interactions. Secondly, age-related changes in pharmacokinetics and pharmacodynamics encountered in older people, particularly frailer ones, predispose to DRPs. Pharmacodynamic changes including alterations in end-organ response to drugs and less efficient homeostatic mechanisms often result in an increased sensitivity to several drug classes, such as anticoagulant, cardiovascular and psychotropic drugs [15]. Thirdly, older people are frequently treated by multiple physicians simultaneously. Often single system specialists are keen to prescribe the best evidence-based therapy for the condition of interest, taking into account the most common comorbidities but, at the same time, failing to consider the complex pharmacotherapy of the patient. Therefore, it can be difficult to preserve a balanced perspective of the prescribed pharmacotherapy with regard to indications, duration of therapy, monitoring of side-effects, multiplicity of prescribing physicians and monitoring of the medication effectiveness for the various indications. Fourthly, inadequate consideration of patients’ characteristics, such as cognitive function, depressed mood, manual dexterity and swallowing capacity might lead to decreased adherence and, consequently, to inappropriate medication omissions with failure to achieve therapeutic targets.
Risk factors for DRPs include multimorbidity, polypharmacy, poor functional status, depression and renal impairment [8]. Previous studies show that about 5–10% of hospital admissions are related to DRPs, of which 50% are preventable [10, 16]. Evidence indicates that pharmacotherapy can be improved in at least 20% of community-dwelling older people [5]. Other consequences of DRPs include reduced quality of life and higher health-related costs relating to increased morbidity and mortality.
Prescribing cascades
A prescribing cascade takes place when an adverse drug event is misconstrued as a new symptom or medical condition for which another drug is subsequently prescribed, placing the patient at risk of additional adverse events arising from this potentially unnecessary treatment [17]. With polypharmacy, it may be difficult to distinguish between drugs prescribed to treat underlying disease and those inappropriately prescribed to treat drug-related side-effects, i.e. cascades. Therefore, to avoid prescribing cascades, physicians should consider any new symptom, until proven otherwise, as a possible effect of current pharmacotherapy. Timely identification and management of prescribing cascades requires a detailed history, including the time of onset of new symptoms in relation to starting or changing medication.
Drug interactions
Drug interactions occur as a result of qualitative or quantitative modification of the effects of a drug caused by the previous or simultaneous administration of other drugs. Recently, an international consensus list of potentially clinically significant drug–drug interactions has been published [18]. Drug interactions may take the form of increased efficacy, decreased efficacy or increased toxicity. A recent observational study of potentially IP in community-dwelling older people with polypharmacy showed that 51% of older patients had at least one clinically relevant interaction [19]. Drug interactions are generally either pharmacokinetic (i.e. one drug affects the absorption, distribution, metabolism or excretion of the other) or pharmacodynamic (i.e. the two drugs have mutually synergistic or antagonistic effects) in nature. The recently developed Ghent Older People’s Prescriptions Community Pharmacy Screening (GheOP3S) instrument to identify potentially IP in community-dwelling older people includes a list of drug interactions with specific relevance for older patients [20], based on their association with unplanned hospital admission.
Inappropriate prescribing
IP is defined as prescribing where the risks outweigh the benefits or as prescribing of drugs for which there is no clear indication or carrying a high risk of side-effects or that is not cost-effective [21]. IP is strongly associated with polypharmacy [1]. A systematic review by Kaufmann et al. identified 46 tools to assess the appropriateness of prescribing published between 1991 and 2013 [22]. Since then, the updates of some of these tools have been published, in addition to several new tools [20, 23–25]. These assessment tools are classified as explicit (criterion-based) or implicit (judgment-based). So far, there is no single ideal IP screening instrument. The implementation of such an instrument requires that it must be evidence-based, well-designed and practical. Integrating prescribing assessment tools into electronic support systems may prove promising if shown to improve patient outcomes. These tools are not, however, a substitute for good clinical decision-making in the treatment of older patients.
Explicit tools
Explicit tools that only consider prescribing or clinical data are often used to identify potentially IP. They are based on lists of potentially inappropriate drugs, i.e. drugs that should be avoided in older people because their associated risks outweigh their benefits [21]. Several explicit tools are available, although only Beers criteria and STOPP/START criteria have been evaluated for predictive validity. It should be noted that, compared with the Beers criteria, only STOPP/START criteria evaluate underprescription, can predict adverse drug reactions and through an intervention based on their application can reduce IP and adverse drug reactions [23]. Explicit criteria can be applied with little or no clinical judgment and do not address individual differences between patients. In terms of their relevance to daily practice, these criteria generally do not take into account co-morbidities commonly found in older patients, nor do they evaluate patient preferences or experiences with previous treatments.
Implicit tools
Implicit tools incorporate clinical information from the individual patient to assess the appropriateness of the patient’s medication. The medication appropriateness index (MAI) was the first validated implicit instrument [26]. MAI assesses 10 elements of prescribing: indication, effectiveness, dose, correct directions, practical directions, drug–drug and drug–disease interactions, dual therapy, duration of therapy and cost. These elements are assessed through clinical judgment leading to a weighted score that serves as a summary measure of prescribing appropriateness. Implicit criteria are more time-consuming and are highly user-dependent.
Identifying drug-related problems and optimizing inappropriate prescribing
Drug reconciliation is the initial essential task in identifying potentially IP. It is defined as ‘a process of obtaining and verifying a complete and accurate list of all of the patient’s current medications—including name, dosage, frequency and route of administration’ [27]. Drug reconciliation constitutes the first part of structured medication review. This step-by-step approach to optimizing pharmacotherapy in older people consists of medication review, defined as ‘a structured, critical review of a patient’s drugs with the aim of reaching agreement with the patient on treatment, optimizing the effect of drugs, reducing the number of DRPs, minimizing and reducing waste’ [28]. This is followed by application of criteria for identifying and preventing inappropriate medication, implementation of computer-based prescribing systems and finally, comprehensive geriatric assessment and management. Most published studies describe single interventions targeting either clinical or pharmacological factors that mediate the occurrence of potentially IP and DRPs. When these interventions are combined, positive effects on patient-related outcomes can be expected. Integration of skills from different healthcare providers is therefore considered essential to address the medical complexity of older patients. A challenge for future research is how to integrate important clinical information obtained by existing methods into a comprehensive and wide-reaching approach targeting all potential factors involved in causing DRPs.
One of the major challenges in setting therapeutic goals in older patients is an assessment of the expected benefits versus risks of a treatment in a population with reduced life expectancy and reduced stress tolerance. Consistent with variation in life expectancy, comprehensive geriatric assessment (CGA) allows identification of three groups of patients, i.e. robust, pre-frail and frail [29, 30]. Robust patients are functionally independent with no relevant comorbidities in whom full therapy to achieve results comparable to younger patients is usually appropriate. Pre-frail patients are those with low dependence in instrumental activities of daily living (ADL) and/or one or two comorbidities in the absence of a geriatric syndrome or dependence on ADL for whom adapted/tailored pharmacotherapy, including judicious deprescribing is usually indicated. Frail patients are characterized by one or more of the following elements: multiple comorbidities, the presence of one or more geriatric syndromes, or dependence in ADL. They are generally aged 85 years or older and may benefit from deprescribing and symptom palliation.
In conclusion, there are several aspects to consider when prescribing appropriately for older people. One should prescribe only when necessary, and weigh benefits against risks. It is essential to involve the patient and when necessary, his/her family in choices about their care whilst respecting the patient’s autonomy. The patient’s age, medical history (particularly any liver and/or renal insufficiency) and any concomitant medication are critical considerations and selecting the correct dosage of every drug is essential.
Good prescribing in late life accommodates the needs of older patients with multimorbidity. Individualized, interactive, multidisciplinary, and multifaceted approach to geriatric pharmacotherapy should be promoted and encouraged. How to optimize pharmacological prescription in complex older patients is a major legacy of geriatrics to contemporary medical practice.
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Declaration of Conflicts of Interest
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