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The term polypharmacy generally refers to the use of multiple medications by a patient. The term is used 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 reactions, drug-drug interactions and higher costs. Polypharmacy is most common in the elderly but is also widespread in the general population.

Pill burden

Pill burden is a term that refers to the number of tablets, capsules or other dosage forms 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 it 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, an 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 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.

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.

At risk demographic groups

Patients at greatest risk of 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.

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 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.

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.


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


  1. Fulton MM, Allen ER. Polypharmacy in the elderly: a literature review. J Am Acad Nurse Pract 2005;17:123-32. PMID 15819637.
  2. Mandell, A.J. and Selz, K.A. 1992 Dynamical systems in psychiatry: Now what? Biological Psychiatry 32: 299-301.
  3. Callahan, J. and Sashin, J. I. 1987 Models of affect-response and anorexia nervosa. Ann. N.Y. Acad. Sci. 504:241-259.
  4. Zarowitz BJ, Stebelsky LA, Muma BK, Romain TM, Peterson EL. Reduction of high-risk polypharmacy drug combinations in patients in a managed care setting. Pharmacotherapy 2005;25:1636-45. PMID 16232025.

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