polypharmacy polypharmacy polypharmacy (polypragmasia) is an umbrella term to describe the simultaneous use of multiple medicines by a patient for their conditions. most commonly it is defined as regularly taking five or more medicines but definitions vary in where they draw the line for the minimum number of drugs. polypharmacy is often the consequence of having multiple long-term conditions, also known as multimorbidity. an excessive number of medications is worrisome, especially for older patients with many chronic health conditions, because this increases the risk of an adverse event in those patients. not to be confused with combination drug. polypharmacy is often defined as taking 5 or more medicines. 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. 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. 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. about 21% of adults with intellectual disability are also exposed to polypharmacy. 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. 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. 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. a prescribing cascade occurs when a patient 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. polypharmacy also increases the burden of medication taking particularly in older people and is associated with medication non-adherence. polypharmacy is often associated with a decreased quality of life, including decreased mobility and cognition. 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. 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. appropriate medical uses while polypharmacy is typically regarded as undesirable, prescription of multiple medications can be appropriate and therapeutically beneficial in some circumstances. “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. 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). 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 is known as an analgesia sparing effect. examples a legitimate treatment regimen in the first year after a myocardial infarction may include: a statin, an ace inhibitor, a beta-blocker, aspirin, paracetamol and an antidepressant. in anesthesia (particularly iv anesthesia and general anesthesia) multiple agents are almost always required – including hypnotics or analgesic inducing/maintenance agents such as midazolam or propofol, usually an opioid analgesic such as morphine or fentanyl, a paralytic such as vecuronium, and in inhaled general anesthesia generally a halogenated ether anesthetic such as sevoflurane or desflurane. special populations people who are at greatest risk for negative polypharmacy consequences include elderly people, people with psychiatric conditions, patients with intellectual or developmental disabilities, 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, people who live in rural communities, people with inadequate access to education, 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. it is not uncommon for people who are dependent or addicted to substances to enter or remain in a state of polypharmacy misuse. about 84% of prescription drug misusers reported using multiple drugs. 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. reducing the number of medications, as part of a clinical review, can be an effective healthcare intervention. 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. 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. risks of polypharmacy the risk of polypharmacy increases with age, although there is some evidence that it may decrease slightly after age 90 years. 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. it appears possible that the risk factors for polypharmacy may be different for younger and middle-aged people compared to older people. 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. 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. 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. polypharmacy is associated with an increased risk of falls in elderly people. certain medications are well known to be associated with the risk of falls, including cardiovascular and psychoactive medications. there is some evidence that the risk of falls increases cumulatively with the number of medications. 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. 15% of older adults are potentially at risk for a major drug-drug interaction. 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. 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. pill burden 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. a recent study found that older adults in long term care are taking an average of 14 to 15 tablets every day. poor medical adherence is a common challenge among individuals who have increased pill burden and are subject to polypharmacy. 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. high pill burden was commonly associated with antiretroviral drug regimens to control hiv, and is also seen in other patient populations. 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. the combination of multiple drugs has been associated with an increased risk of adverse drug events. 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. 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. 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. 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. the development of applications has also shown some benefit in this regard. 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. 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. 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. interventions the most common intervention