Polypharmacy (polypragmasia) is an umbrella term to describe the simultaneous use of multiple medicines by a patient for their conditions. [1] [2] The term polypharmacy is often defined as regularly taking five or more medicines but there is no standard definition and the term has also been used in the context of when a person is prescribed 2 or more medications at the same time. [1] [3] [4] Polypharmacy may be the consequence of having multiple long-term conditions, also known as multimorbidity and is more common in people who are older. [5] [6] In some cases, an excessive number of medications at the same time is worrisome, especially for people who are older with many chronic health conditions, because this increases the risk of an adverse event in that population. [7] [8] In many cases, polypharmacy cannot be avoided, but 'appropriate polypharmacy' practices are encouraged to decrease the risk of adverse effects. [9] Appropriate polypharmacy is defined as the practice of prescribing for a person who has multiple conditions or complex health needs by ensuring that medications prescribed are optimized and follow 'best evidence' practices. [9]
The prevalence of polypharmacy is estimated to be between 10% and 90% depending on the definition used, the age group studied, and the geographic location. [10] Polypharmacy continues to grow in importance because of aging populations. Many countries are experiencing a fast growth of the older population, 65 years and older. [11] [12] [13] This growth is a result of the baby-boomer generation getting older and an increased life expectancy as a result of ongoing improvement in health care services worldwide. [14] [15] About 21% of adults with intellectual disability are also exposed to polypharmacy. [16] The level of polypharmacy has been increasing in the past decades. Research in the USA shows that the percentage of patients greater than 65 years-old using more than 5 medications increased from 24% to 39% between 1999 and 2012. [17] Similarly, research in the UK found that the number of older people taking 5 plus medication had quadrupled from 12% to nearly 50% between 1994 and 2011. [18]
Polypharmacy is not necessarily ill-advised, but in many instances can lead to negative outcomes or poor treatment effectiveness, often being more harmful than helpful or presenting too much risk for too little benefit. Therefore, health professionals consider it a situation that requires monitoring and review to validate whether all of the medications are still necessary. Concerns about polypharmacy include increased adverse drug reactions, drug interactions, prescribing cascade, and higher costs. [19] A prescribing cascade occurs when a person is prescribed a drug and experiences an adverse drug effect that is misinterpreted as a new medical condition, so the patient is prescribed another drug. [20] Polypharmacy also increases the burden of medication taking particularly in older people and is associated with medication non-adherence. [21]
Polypharmacy is often associated with a decreased quality of life, including decreased mobility and cognition. [22] Patient factors that influence the number of medications a patient is prescribed include a high number of chronic conditions requiring a complex drug regimen. Other systemic factors that impact the number of medications a patient is prescribed include a patient having multiple prescribers and multiple pharmacies that may not communicate.
Whether or not the advantages of polypharmacy (over taking single medications or monotherapy) outweigh the disadvantages or risks depends upon the particular combination and diagnosis involved in any given case. [23] The use of multiple drugs, even in fairly straightforward illnesses, is not an indicator of poor treatment and is not necessarily overmedication. Moreover, it is well accepted in pharmacology that it is impossible to accurately predict the side effects or clinical effects of a combination of drugs without studying that particular combination of drugs in test subjects. Knowledge of the pharmacologic profiles of the individual drugs in question does not assure accurate prediction of the side effects of combinations of those drugs; and effects also vary among individuals because of genome-specific pharmacokinetics. Therefore, deciding whether and how to reduce a list of medications (deprescribe) is often not simple and requires the experience and judgment of a practicing clinician, as the clinician must weigh the pros and cons of keeping the patient on the medication. However, such thoughtful and wise review is an ideal that too often does not happen, owing to problems such as poorly handled care transitions (poor continuity of care, usually because of siloed information), overworked physicians and other clinical staff, and interventionism.
While polypharmacy is typically regarded as undesirable, prescription of multiple medications can be appropriate and therapeutically beneficial in some circumstances. [24] “Appropriate polypharmacy” is described as prescribing for complex or multiple conditions in such a way that necessary medicines are used based on the best available evidence at the time to preserve safety and well-being. [24] Polypharmacy is clinically indicated in some chronic conditions, for example in diabetes mellitus, but should be discontinued when evidence of benefit from the prescribed drugs no longer outweighs potential for harm (described below in Contraindications). [24]
Often certain medications can interact with others in a positive way specifically intended when prescribed together, to achieve a greater effect than any of the single agents alone. This is particularly prominent in the field of anesthesia and pain management – where atypical agents such as antiepileptics, antidepressants, muscle relaxants, NMDA antagonists, and other medications are combined with more typical analgesics such as opioids, prostaglandin inhibitors, NSAIDS and others. This practice of pain management drug synergy [25] is known as an analgesia sparing effect.
People who are at greatest risk for negative polypharmacy consequences include elderly people, people with psychiatric conditions, patients with intellectual or developmental disabilities, [28] people taking five or more drugs at the same time, those with multiple physicians and pharmacies, people who have been recently hospitalized, people who have concurrent comorbidities, [29] people who live in rural communities, people with inadequate access to education, [30] and those with impaired vision or dexterity. Marginalized populations may have a greater degrees of polypharmacy, which can occur more frequently in younger age groups. [31]
It is not uncommon for people who are dependent or addicted to substances to enter or remain in a state of polypharmacy misuse. [32] About 84% of prescription drug misusers reported using multiple drugs. [32] Note, however, that the term polypharmacy and its variants generally refer to legal drug use as-prescribed, even when used in a negative or critical context.
Measures can be taken to limit polypharmacy to its truly legitimate and appropriate needs. This is an emerging area of research, frequently called deprescribing. [33] Reducing the number of medications, as part of a clinical review, can be an effective healthcare intervention. [34] Clinical pharmacists can perform drug therapy reviews and teach physicians and their patients about drug safety and polypharmacy, as well as collaborating with physicians and patients to correct polypharmacy problems. Similar programs are likely to reduce the potentially deleterious consequences of polypharmacy such as adverse drug events, non-adherence, hospital admissions, drug-drug interactions, geriatric syndromes, and mortality. [35] Such programs hinge upon patients and doctors informing pharmacists of other medications being prescribed, as well as herbal, over-the-counter substances and supplements that occasionally interfere with prescription-only medication. Staff at residential aged care facilities have a range of views and attitudes towards polypharmacy that, in some cases, may contribute to an increase in medication use. [36]
The risk of polypharmacy increases with age, although there is some evidence that it may decrease slightly after age 90 years. [2] Poorer health is a strong predictor of polypharmacy at any age, although it is unclear whether the polypharmacy causes the poorer health or if polypharmacy is used because of the poorer health. [2] It appears possible that the risk factors for polypharmacy may be different for younger and middle-aged people compared to older people. [2]
The use of polypharmacy is correlated to the use of potentially inappropriate medications. Potentially inappropriate medications are generally taken to mean those that have been agreed upon by expert consensus, such as by the Beers Criteria. These medications are generally inappropriate for older adults because the risks outweigh the benefits. [37] Examples of these include urinary anticholinergics used to treat incontinence; the associated risks, with anticholinergics, include constipation, blurred vision, dry mouth, impaired cognition, and falls. [38] Many older people living in long term care facilities experience polypharmacy, and under-prescribing of potentially indicated medicines and use of high risk medicines can also occur. [37] Medicine use rises from 6.0 ± 3.8 regular medicines on average when people enter long term care to 8.9 ± 4.1 regular medicines after two years. [39]
Polypharmacy is associated with an increased risk of falls in elderly people. [40] [41] Certain medications are well known to be associated with the risk of falls, including cardiovascular and psychoactive medications. [42] [43] There is some evidence that the risk of falls increases cumulatively with the number of medications. [44] [45] Although often not practical to achieve, withdrawing all medicines associated with falls risk can halve an individual's risk of future falls.
Every medication has potential adverse side-effects. With every drug added, there is an additive risk of side-effects. Also, some medications have interactions with other substances, including foods, other medications, and herbal supplements. [46] 15% of older adults are potentially at risk for a major drug-drug interaction. [47] Older adults are at a higher risk for a drug-drug interaction due to the increased number of medications prescribed and metabolic changes that occur with aging. [48] When a new drug is prescribed, the risk of interactions increases exponentially. Doctors and pharmacists aim to avoid prescribing medications that interact; often, adjustments in the dose of medications need to be made to avoid interactions. For example, warfarin interacts with many medications and supplements that can cause it to lose its effect. [48] [49]
Pill burden is the number of pills (tablets or capsules, the most common dosage forms) that a person takes on a regular basis, along with all associated efforts that increase with that number - like storing, organizing, consuming, and understanding the various medications in one's regimen. The use of individual medications is growing faster than pill burden. [50] A recent study found that older adults in long term care are taking an average of 14 to 15 tablets every day. [51]
Poor medical adherence is a common challenge among individuals who have increased pill burden and are subject to polypharmacy. [52] It also increases the possibility of adverse medication reactions (side effects) and drug-drug interactions. High pill burden has also been associated with an increased risk of hospitalization, medication errors, and increased costs for both the pharmaceuticals themselves and for the treatment of adverse events. Finally, pill burden is a source of dissatisfaction for many patients and family carers. [21]
High pill burden was commonly associated with antiretroviral drug regimens to control HIV, [53] and is also seen in other patient populations. [52] For instance, adults with multiple common chronic conditions such as diabetes, hypertension, lymphedema, hypercholesterolemia, osteoporosis, constipation, inflammatory bowel disease, and clinical depression may be prescribed more than a dozen different medications daily. [54] The combination of multiple drugs has been associated with an increased risk of adverse drug events. [55]
Reducing pill burden is recognized as a way to improve medication compliance, also referred to as adherence. This is done through "deprescribing", where the risks and benefits are weighed when considering whether to continue a medication. [56] This includes drugs such as bisphosphonates (for osteoporosis), which are often taken indefinitely although there is only evidence to use it for five to ten years. [56] Patient educational programs, reminder messages, medication packaging, and the use of memory tricks has also been seen to improve adherence and reduce pill burden in several countries. [48] These include associating medications with mealtimes, recording the dosage on the box, storing the medication in a special place, leaving it in plain sight in the living room, or putting the prescription sheet on the refrigerator. [48] The development of applications has also shown some benefit in this regard. [48] The use of a polypill regimen, such as combination pill for HIV treatment, as opposed to a multi-pill regimen, also alleviates pill burden and increases adherence. [52]
The selection of long-acting active ingredients over short-acting ones may also reduce pill burden. For instance, ACE inhibitors are used in the management of hypertension.[ medical citation needed ] Both captopril and lisinopril are examples of ACE inhibitors. However, lisinopril is dosed once a day, whereas captopril may be dosed 2-3 times a day. Assuming that there are no contraindications or potential for drug interactions, using lisinopril instead of captopril may be an appropriate way to limit pill burden.[ medical citation needed ]
The most common intervention to help people who are struggling with polypharmacy is deprescribing. [57] Deprescribing can be confused with medication simplification, which does not attempt to reduce the number of medicines but rather reduce the number of dose forms and administration times. [58] Deprescribing refers to reducing the number of medications that a person is prescribed and includes the identification and discontinuance of medications when the benefit no longer outweighs the harm. [59] In elderly patients, this can commonly be done as a patient becomes more frail and treatment focus needs to shift from preventative to palliative. [59] Deprescribing is feasible and effective in many settings including residential care, communities and hospitals. [57] This preventative measure should be considered for anyone who exhibits one of the following: (1) a new symptom or adverse event arises, (2) when the person develops an end-stage disease, (3) if the combination of drugs is risky, or (4) if stopping the drug does not alter the disease trajectory. [9]
Several tools exist to help physicians decide when to deprescribe and what medications can be added to a pharmaceutical regimen. The Beers Criteria and the STOPP/START criteria help identify medications that have the highest risk of adverse drug events (ADE) and drug-drug interactions. [60] [61] [62] The Medication appropriateness tool for comorbid health conditions during dementia (MATCH-D) is the only tool available specifically for people with dementia, and also cautions against polypharmacy and complex medication regimens. [63] [64]
Barriers faced by both physicians and people taking the medications have made it challenging to apply deprescribing strategies in practice. [65] For physicians, these include fear of consequences of deprescribing, the prescriber's own confidence in their skills and knowledge to deprescribe, reluctance to alter medications that are prescribed by specialists, the feasibility of deprescribing, lack of access to all of patients' clinical notes, and the complexity of having multiple providers. [65] [66] [67] For patients who are prescribed or require the medication, barriers include attitudes or beliefs about the medications, inability to communicate with physicians, fears and uncertainties surrounding deprescribing, and influence of physicians, family, and the media. [65] Barriers can include other health professionals or carers, such as in residential care, believing that the medicines are required. [68]
In people with multiple long-term conditions (multimorbidity) and polypharmacy deprescribing represents a complex challenge as clinical guidelines are usually developed for single conditions. In these cases tools and guidelines like the Beers Criteria and STOPP/START could be used safely by clinicians but not all patients might benefit from stopping their medication. There is a need for clarity about how much clinicians can do beyond the guidelines and the responsibility they need to take could help them prescribing and deprescribing for complex cases. Further factors that can help clinicians tailor their decisions to the individual are: access to detailed data on the people in their care (including their backgrounds and personal medical goals), discussing plans to stop a medicine already when it is first prescribed, and a good relationship that involves mutual trust and regular discussions on progress. Furthermore, longer appointments for prescribing and deprescribing would allow time explain the process of deprescribing, explore related concerns, and support making the right decisions. [69] [70]
The effectiveness of specific interventions to improve the appropriate use of polypharmacy such as pharmaceutical care and computerised decision support is unclear. [9] This is due to low quality of current evidence surrounding these interventions. [9] High quality evidence is needed to make any conclusions about the effects of such interventions in any environment, including in care homes. [71] Deprescribing is not influenced by whether medicines are prescribed through a paper-based or an electronic system. [72] Deprescribing rounds has been proposed as a potentially successful methodology in reducing polypharmacy. [73] Sharing of positive outcomes from physicians who have implemented deprescribing, increased communication between all practitioners involved in patient care, higher compensation for time spent deprescribing, and clear deprescribing guidelines can help enable the practice of deprescribing. [67] Despite the difficulties, a recent blinded study of deprescribing reported that participants used an average of two fewer medicines each after 12 months showing again that deprescribing is feasible. [74]
Benzodiazepines, colloquially known as "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and was made available in 1960 by Hoffmann–La Roche, which followed with the development of diazepam (Valium) three years later, in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.
Hypnotic, or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness).
Geriatrics, or geriatric medicine, is a medical specialty focused on providing care for the unique health needs of the elderly. The term geriatrics originates from the Greek γέρων geron meaning "old man", and ιατρός iatros meaning "healer". It aims to promote health by preventing, diagnosing and treating disease in older adults. There is no defined age at which patients may be under the care of a geriatrician, or geriatric physician, a physician who specializes in the care of older people. Rather, this decision is guided by individual patient need and the caregiving structures available to them. This care may benefit those who are managing multiple chronic conditions or experiencing significant age-related complications that threaten quality of daily life. Geriatric care may be indicated if caregiving responsibilities become increasingly stressful or medically complex for family and caregivers to manage independently.
An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or may result from the combination of two or more drugs. The meaning of this term differs from the term "side effect" because side effects can be beneficial as well as detrimental. The study of ADRs is the concern of the field known as pharmacovigilance. An adverse event (AE) refers to any unexpected and inappropriate occurrence at the time a drug is used, whether or not the event is associated with the administration of the drug. An ADR is a special type of AE in which a causative relationship can be shown. ADRs are only one type of medication-related harm. Another type of medication-related harm type includes not taking prescribed medications, known as non-adherence. Non-adherence to medications can lead to death and other negative outcomes. Adverse drug reactions require the use of a medication.
Nonbenzodiazepines, sometimes referred to colloquially as Z-drugs, are a class of psychoactive, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as for treating insomnia and anxiety.
Medication discontinuation is the ceasing of a medication treatment for a patient by either the clinician or the patient themself. When initiated by the clinician, it is known as deprescribing. Medication discontinuation is an important medical practice that may be motivated by a number of reasons:
In medicine, patient compliance describes the degree to which a patient correctly follows medical advice. Most commonly, it refers to medication or drug compliance, but it can also apply to other situations such as medical device use, self care, self-directed exercises, or therapy sessions. Both patient and health-care provider affect compliance, and a positive physician-patient relationship is the most important factor in improving compliance. Access to care plays a role in patient adherence, whereby greater wait times to access care contributing to greater absenteeism. The cost of prescription medication also plays a major role.
The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, commonly called the Beers List, are guidelines published by the American Geriatrics Society (AGS) for healthcare professionals to help improve the safety of prescribing medications for adults 65 years and older in all except palliative settings. They emphasize deprescribing medications that are unnecessary, which helps to reduce the problems of polypharmacy, drug interactions, and adverse drug reactions, thereby improving the risk–benefit ratio of medication regimens in at-risk people.
Fall prevention includes any action taken to help reduce the number of accidental falls suffered by susceptible individuals, such as the elderly and people with neurological or orthopedic indications.
Multimorbidity, also known as multiple long-term conditions (MLTC), means living with two or more chronic illnesses. For example, a person could have diabetes, heart disease and depression at the same time. Multimorbidity can have a significant impact on people's health and wellbeing. It also poses a complex challenge to healthcare systems which are traditionally focused on individual diseases. Multiple long-term conditions can affect people of any age, but they are more common in older age, affecting more than half of people over 65 years old.
Overmedication describes the excessive use of over-the-counter or prescription medicines for a person. Overmedication can have harmful effects, such as non-adherence or interactions with multiple prescription drugs.
Accidental (CDI), or multiple drug intake (MDI), is a cause of death by drug overdose from poly drug use, often implicated in polysubstance dependence.
Prescription cascade is the process whereby the side effects of drugs are misdiagnosed as symptoms of another problem, resulting in further prescriptions and further side effects and unanticipated drug interactions, which itself may lead to further symptoms and further misdiagnoses. This is a pharmacological example of a feedback loop. Such cascades can be reversed through deprescribing.
Pharmacoepidemiology is the study of the uses and effects of drugs in well-defined populations.
Medication therapy management, generally called medicine use review in the United Kingdom, is a service provided typically by pharmacists, medical affairs, and RWE scientists that aims to improve outcomes by helping people to better understand their health conditions and the medications used to manage them. This includes providing education on the disease state and medications used to treat the disease state, ensuring that medicines are taken correctly, reducing waste due to unused medicines, looking for any side effects, and providing education on how to manage any side effects. The process that can be broken down into five steps: medication therapy review, personal medication record, medication-related action plan, intervention and or referral, and documentation and follow-up.
Deprescribing is a process of tapering or stopping medications to achieve improved health outcomes by reducing exposure to medications that are potentially either harmful or no longer required. Deprescribing is important to consider with changing health and care goals over time, as well as polypharmacy and adverse effects. Deprescribing can improve adherence, cost, and health outcomes but may have adverse drug withdrawal effects. More specifically, deprescribing is the planned and supervised process of intentionally stopping a medication or reducing its dose to improve the person's health or reduce the risk of adverse side effects. Deprescribing is usually done because the drug may be causing harm, may no longer be helping the patient, or may be inappropriate for the individual patient's current situation. Deprescribing can help correct polypharmacy and prescription cascade.
The Medication Appropriateness Tool for Comorbid Health conditions during Dementia (MATCH-D) criteria supports clinicians to manage medication use specifically for people with dementia without focusing only on the management of the dementia itself.
Cara Tannenbaum is a Canadian researcher and physician in the fields of geriatrics, women's health, and gender research. From 2015-2022, Tannenbaum served as the Scientific Director of Canadian Institutes of Health Research's Institute of Gender and Health. She was appointed as a Member of the Order of Canada on November 17, 2021.
Somnifacient, also known as sedatives or sleeping pills, is a class of medications that induces sleep. It is mainly used for treatment of insomnia. Examples of somnifacients include benzodiazepines, barbiturates and antihistamines.
Prescription drugoveruse or non-medical prescription drug use is the use of prescription medications that is more than the prescribed amount, regardless of whether the original medical reason to take the drug is legitimate. A prescription drug is a drug substance prescribed by a doctor and intended to for individual use only.
The use of multiple drugs or medicines for several concurrent disorders (now esp. by elderly patients), often with the suggestion of indiscriminate, unscientific, or excessive prescription.
1 The administration of many drugs at the same time. 2 The administration of an excessive number of drugs.
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