Polypharmacy is the use of multiple medications by a patient, generally older adults (those aged over 65 years). More specifically, it is often defined as the use of five or more regular medications. It sometimes alternatively refers to purportedly excessive or unnecessary prescriptions. The term polypharmacy lacks a universally consistent definition. Polypharmacy is most common in the elderly, affecting about 40% of older adults living in their own homes.
Although polypharmacy can be appropriate, it is more often inappropriate. Concerns about polypharmacy include increased adverse drug reactions, drug-drug interactions, prescribing cascade, and higher costs. Polypharmacy is often associated with a decreased quality of life, decreased mobility and cognition.
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.
Whether or not the advantages of polypharmacy (over 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. A perfectly legitimate treatment regimen could include, for example, the following: a statin, an ACEI inhibitor, a beta-blocker, aspirin, paracetamol and an antidepressant in the first year after a myocardial infarction.
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, which can prevent up to one episode of incontinence every 48 hours on average. However, they can also cause constipation, dry eyes, dry mouth, impaired cognition, and increase the risk of falls.
Polypharmacy is associated with an increased risk of falls in the elderly. Certain medications are well known to be associated with the risk of falls, including cardiovascular and psychoactive medications. The use of four or more of these medicines is known to be associated with a significantly higher, cumulative risk of falls. 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, 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.
Patients at greatest risk for negative polypharmacy consequences include the elderly, psychiatric patients, patients taking five or more drugs concurrently, those with multiple physicians and pharmacies, recently hospitalized patients, individuals with concurrent comorbidities, low educational level, and those with impaired vision or dexterity.
It is not uncommon for those dependent or addicted to substances to enter or remain in a state of polypharmacy misuse. 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. 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.
Considerations often associated with thoughtful, therapeutic polypharmacy include: (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.
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 sparing effect.
As another example, 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.
Pill burden is a term that refers to the number of pills (tablets or capsules, the most common dosage forms) that a patient 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.
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. 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) where it is often used indefinitely although there is only evidence to use it for five to ten years.
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.
- Mandell, A.J. and Selz, K.A. 1992 Dynamical systems in psychiatry: Now what? Biological Psychiatry 32: 299-301.
- Callahan, J. and Sashin, J. I. 1987 Models of affect-response and anorexia nervosa. Ann. N.Y. Acad. Sci. 504:241-259.
- American Nurses Association 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 Hill School of Medicine
-  - “Appropriate Prescribing for Patients and Polypharmacy Guidance for Review of Quality, Safe and Effective Use of Long-term Medication.” Scotland NHS, 2012