Polypharmacy
Encyclopedia
Polypharmacy is the use of multiple medication
s by a patient, especially when too many forms of medication are used by a patient, when more drugs
are prescribed than is clinically warranted, or even when all prescribed medications are clinically indicated but there are too many pills to take (pill burden). Furthermore, a portion of the treatments may not be evidence-based
. The most common results of polypharmacy are increased adverse drug reaction
s, drug-drug interactions and higher costs. Polypharmacy is most common in the elderly but is also widespread in the general population.
Polypharmacy is most common in people with multiple medical conditions. Combination therapy
is the use of multiple drugs specifically to treat a single medical condition; monotherapy is the use of a single drug.
s that a patient takes on a regular basis.
High pill burden decreases compliance
with drug therapy, resulting from the need to take a large quantity of pills or other forms of medication on a regular basis. 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.
High pill burden is commonly associated with antiretroviral drug
regimens to control HIV
, but can be seen in other patient populations. For instance, adults with multiple chronic conditions such as diabetes, hypertension
, lymphedema
, hypercholesterolemia
, osteoporosis
, constipation
, and clinical depression
can often be prescribed more than a dozen different medications daily. The adverse reactions of these combinations of drugs are not reliably predictable. Obesity
is implicated in many of the aforementioned conditions, and it is not uncommon for a clinically obese patient to receive pharmacologic treatment for all of these. Because chronic conditions tend to accumulate in the elderly, pill burden is a particular issue in geriatrics
.
Reducing pill burden is recognized as a way to improve medication compliance. Common approaches for reducing pill burden include selecting fixed dose combination
drug products, products with long-acting active ingredients, and sustained release/extended release
formulations when appropriate.
Some combinations of drugs may be available in certain strengths as a single pill, called a fixed dose combination
. One notable example of a fixed dose combination drug product is the antiretroviral drug product Atripla
, which combines 3 drugs (efavirenz
+ emtricitabine
+ tenofovir) into one pill.
The selection of long-acting active ingredients over short-acting ones may also reduce pill burden. For instance, ACE inhibitor
s 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.
Similarly, sustained release/extended release
drug formulations reduce pill burden by reducing the dosing frequency. The same active ingredient is present in both the immediate-release form and the sustained release form.
patients, patients taking five or more drugs concurrently, those with multiple physician
s and pharmacies
, recently hospitalized patients, individuals with concurrent comorbidities
, low educational level, and those with impaired vision or dexterity.
Many medications have potential interactions
with other substances. As 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, such as with warfarin
, as it may lose its effect.
Two generally true circumstances underlie the theory of thoughtful, therapeutic polypharmacy: (1) Drugs given for a single somatic locale act on biochemical mechanisms present throughout the body such that their nonlinear interactions can produce an (unknown except empirically) global physiological state of health; (2) The more independent variables, "handles", to manipulate, the greater the likelihood of finding and stabilizing a small available parametric space of healthy function while minimizing unwanted effects.
The use of multiple pharmaceuticals to treat a single illness is often the result of a healthcare practitioner attempting, usually through trial and error, to obtain the highest efficacy through the concept of drug synergy. Often certain medications can interact with others in a positive way specifically intended when prescribed together to achieve a greater effect that 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 sparring effect. In anesthesia, particularly IV anesthesia and General anesthesia, multiple agents are almost always required, including hypnotics or analgesic inducing/maintenance agents such as Versed or Diprivan, usually an opioid analgesic such as morphine or Demerol, a paralytic such as vecuronium, and in inhaled general anesthesia generally a halogenated ether anesthetic such as sevoflurane or desflurane.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s by a patient, especially when too many forms of medication are used by a patient, when more drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
are prescribed than is clinically warranted, or even when all prescribed medications are clinically indicated but there are too many pills to take (pill burden). Furthermore, a portion of the treatments may not be evidence-based
Evidence-based medicine
Evidence-based medicine or evidence-based practice aims to apply the best available evidence gained from the scientific method to clinical decision making. It seeks to assess the strength of evidence of the risks and benefits of treatments and diagnostic tests...
. The most common results of polypharmacy are increased adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s, drug-drug interactions and higher costs. Polypharmacy is most common in the elderly but is also widespread in the general population.
Polypharmacy is most common in people with multiple medical conditions. Combination therapy
Combination therapy
Combination therapy or polytherapy is the use of more than one medication or other therapy. In contrast, monotherapy is any therapy which is taken by itself....
is the use of multiple drugs specifically to treat a single medical condition; monotherapy is the use of a single drug.
Pill burden
Pill burden is a term that refers to the number of tablets, capsules or other dosage formDosage form
-Introduction:Dosage forms are a mixture of active drug components and nondrug components. Depending on the method of administration they come in several types. These are liquid dosage form, solid dosage form and semisolid dosage forms. A Liquid dosage form is the liquid form of a dose of a...
s that a patient takes on a regular basis.
High pill burden decreases compliance
Compliance (medicine)
In medicine, compliance describes the degree to which a patient correctly follows medical advice...
with drug therapy, resulting from the need to take a large quantity of pills or other forms of medication on a regular basis. It also increases the possibility of adverse medication reactions (side effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
) and drug-drug interactions
Drug interaction
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind...
. 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.
High pill burden is commonly associated with antiretroviral drug
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...
regimens to control HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, but can be seen in other patient populations. For instance, adults with multiple chronic conditions such as diabetes, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, lymphedema
Lymphedema
Lymphedema , also known as lymphatic obstruction, is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system....
, hypercholesterolemia
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
, osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, and clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
can often be prescribed more than a dozen different medications daily. The adverse reactions of these combinations of drugs are not reliably predictable. Obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
is implicated in many of the aforementioned conditions, and it is not uncommon for a clinically obese patient to receive pharmacologic treatment for all of these. Because chronic conditions tend to accumulate in the elderly, pill burden is a particular issue in geriatrics
Geriatrics
Geriatrics is a sub-specialty of internal medicine and family medicine that focuses on health care of elderly people. It aims to promote health by preventing and treating diseases and disabilities in older adults. There is no set age at which patients may be under the care of a geriatrician, or...
.
Reducing pill burden is recognized as a way to improve medication compliance. Common approaches for reducing pill burden include selecting fixed dose combination
Fixed dose combination
A combination drug or fixed-dose combination is a formulation of two or more active ingredients combined in a single dosage form, available in certain fixed doses...
drug products, products with long-acting active ingredients, and sustained release/extended release
Sustained release
Time release technology, also known as sustained-release , sustained-action , extended-release , time-release or timed-release, controlled-release , modified release , or continuous-release , is a mechanism used in pill tablets or capsules to...
formulations when appropriate.
Some combinations of drugs may be available in certain strengths as a single pill, called a fixed dose combination
Fixed dose combination
A combination drug or fixed-dose combination is a formulation of two or more active ingredients combined in a single dosage form, available in certain fixed doses...
. One notable example of a fixed dose combination drug product is the antiretroviral drug product Atripla
Atripla
Emtricitabine/tenofovir/efavirenz is a fixed-dose combination drug for the treatment of HIV infection. It combines Gilead Sciences's tenofovir and emtricitabine with Bristol-Myers Squibb's efavirenz into a fixed-dose pill...
, which combines 3 drugs (efavirenz
Efavirenz
Efavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1....
+ emtricitabine
Emtricitabine
Emtricitabine , with trade name Emtriva , is a nucleoside reverse transcriptase inhibitor for the treatment of HIV infection in adults and children....
+ tenofovir) into one pill.
The selection of long-acting active ingredients over short-acting ones may also reduce pill burden. For instance, ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s are used in the management of hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. Both captopril
Captopril
Captopril is an angiotensin-converting enzyme inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the...
and lisinopril
Lisinopril
Lisinopril is a drug of the angiotensin-converting enzyme inhibitor class that is primarily used in treatment of hypertension, congestive heart failure, and heart attacks and also in preventing renal and retinal complications of diabetes. Its indications, contraindications and side effects are as...
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.
Similarly, sustained release/extended release
Sustained release
Time release technology, also known as sustained-release , sustained-action , extended-release , time-release or timed-release, controlled-release , modified release , or continuous-release , is a mechanism used in pill tablets or capsules to...
drug formulations reduce pill burden by reducing the dosing frequency. The same active ingredient is present in both the immediate-release form and the sustained release form.
At risk demographic groups
Patients at greatest risk of polypharmacy consequences include the elderly, psychiatricPsychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
patients, patients taking five or more drugs concurrently, those with multiple physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s and pharmacies
Pharmacy
Pharmacy is the health profession that links the health sciences with the chemical sciences and it is charged with ensuring the safe and effective use of pharmaceutical drugs...
, recently hospitalized patients, individuals with concurrent comorbidities
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
, low educational level, and those with impaired vision or dexterity.
Adverse reactions and interactions
Every medication has potential adverse side-effects. With every drug added, there is an additive risk of side-effects.Many medications have potential interactions
Drug interaction
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind...
with other substances. As a new drug is prescribed, the risk of interactions increases exponentially. Doctors and pharmacists
Pharmacy
Pharmacy is the health profession that links the health sciences with the chemical sciences and it is charged with ensuring the safe and effective use of pharmaceutical drugs...
aim to avoid prescribing medications that interact; often, adjustments in the dose of medications need to be made to avoid interactions, such as with warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, as it may lose its effect.
Thoughtful versus thoughtless polypharmacy
A patient with a complex or even an ostensibly straightforward illness whose personal pharmacopoeia reads like a drug store pharmacy is not necessarily receiving poor treatment. A carefully followed patient with whom a physician is using additive drug choice and dosage range on a trial and error basis may lead to a treatment program that, for a real example, includes two antidepressants, three antihypertensives, a beta blocker, a calcium channel blocker, a bone saving bisphosphonate, an antiepileptic, a stomach saving H2 blocker, aspirin, prostaglandin blocker, lactoferrin, a calcium-magnesium supplement and herbal preparations.Two generally true circumstances underlie the theory of thoughtful, therapeutic polypharmacy: (1) Drugs given for a single somatic locale act on biochemical mechanisms present throughout the body such that their nonlinear interactions can produce an (unknown except empirically) global physiological state of health; (2) The more independent variables, "handles", to manipulate, the greater the likelihood of finding and stabilizing a small available parametric space of healthy function while minimizing unwanted effects.
The use of multiple pharmaceuticals to treat a single illness is often the result of a healthcare practitioner attempting, usually through trial and error, to obtain the highest efficacy through the concept of drug synergy. Often certain medications can interact with others in a positive way specifically intended when prescribed together to achieve a greater effect that 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 sparring effect. In anesthesia, particularly IV anesthesia and General anesthesia, multiple agents are almost always required, including hypnotics or analgesic inducing/maintenance agents such as Versed or Diprivan, usually an opioid analgesic such as morphine or Demerol, a paralytic such as vecuronium, and in inhaled general anesthesia generally a halogenated ether anesthetic such as sevoflurane or desflurane.
Misuse
It is not uncommon for those dependent or addicted to substances to enter or remain in a state of polypharmacy misuse. One of the best examples includes those who chronically or acutely binge on amphetamines or other psychostimulants (particularly those with long half lives such as the amphetamines and methylphenidate). Because these agents have the effect of reducing or eliminating sleep for long periods of time, when sleep is finally desired or in an effort to reduce the "crash," hypnotics such as benzodiazepines, sometimes opiates, and less frequently barbiturates are used to induce sleep and/or hypnosis. Another classic example of concurrent polypharmacy misuse is the "speedball," a solution of typically cocaine and heroin in the same syringe which is injected together. Other combinations like amphetamines, methylphenidate and morphine, oxycodone, hydrocodone etc are also used and sometimes taken orally. The classic combination of cocaine and heroin injection has resulted in numerous high profile deaths as the stimulant effect of cocaine (which has a notably short half life) last much shorter than the depressant effects of opiates, which can then induce respiratory depression, respiratory arrest, and death.Solutions
Zarowitz et al. studied clinical pharmacists performing drug therapy reviews and the teaching of physicians and their patients about drug safety and polypharmacy, as well as collaborating with physicians and patients to correct polypharmacy problems. This led to a marked improvement in interactions and cost. Similar programs are likely to reduce the potentially deleterious consequences of polypharmacy. 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.See also
- Adverse effectAdverse effect (medicine)In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
- Classification of Pharmaco-Therapeutic ReferralsClassification of Pharmaco-Therapeutic ReferralsThe Classification of Pharmaco-Therapeutic Referrals is a taxonomy focused to define and group together situations requiring a referral from pharmacists to physicians regarding the pharmacotherapy used by the patients. It has been published in 2008...
- ComplianceCompliance (medicine)In medicine, compliance describes the degree to which a patient correctly follows medical advice...
External links
- American Nurses AssociationAmerican Nurses AssociationThe American Nurses Association is a professional organization to advance and protect the profession of nursing. It started in 1896 as the Nurses Associated Alumnae and was renamed the American Nurses Association in 1911...
Position Statement on Polypharmacy and the Older Adult - NASMHPD.org (pdf) - 'Technical Report on Psychiatric Polypharmacy' National Association of State Mental Health Program Directors, (October 9, 2001)
- PsychRights.org - 'Psychiatric Polypharmacy: A Word of Caution', Leslie Morrison, MS, RN, Esq, Paul B. Duryea, Charis Moore, Alexandra Nathanson-Shinn, Stephen E. Hall, MD, James Meeker, PhD, DABFT, Charles A. Reynolds, PharmD, BCPP, Protection & Advocacy, Inc.
- "Polypharmacy in Older Adults: Information for people who are taking several medications", University of North Carolina at Chapel HillUniversity of North Carolina at Chapel HillThe University of North Carolina at Chapel Hill is a public research university located in Chapel Hill, North Carolina, United States...
School of Medicine