Polypharmacy
To examine
Gina DeSevo Bellotti and Emily R.
Hajjar
Thomas Jefferson University, USA
Polypharmacy is a well-documented drug-
related problem particularly in older adults.
Two main definitions for polypharmacy can
be found in the medical literature. The first
definition involves the quantity of medications
a person is taking at one given time. The exact
number of medications deemed to consti-
tute polypharmacy varies by source and may
range from greater than two medications to
greater than 10 medications (Hajjar, Cafiero,
& Hanlon, 2007; Rollason & Vogt, 2003). This
definition does not take into account the fact
that patients may have multiple medical con-
ditions and thus require multiple medications
in order to be adequately treated. In simply
looking at the quantity, practitioners may be
overlooking the appropriateness of the med-
ications. Therefore, the second definition of
polypharmacy is the use of more medications
than are clinically indicated or the use of med-
ications that are medically unnecessary for a
particular patient (Hajjar et al., 2007; Maher,
Hanlon, & Hajjar, 2014; Rollason & Vogt,
2003). This definition requires a review of a
patient’s medication list to determine whether
or not the patient is taking medications that
are not necessary based on the patient’s cur-
rent health status. Examples of unnecessary
medications may include medications with no
indication or medications lacking efficacy.
Prevalence
Because of the varying definitions of polyphar-
macy, determining its prevalence is chal-
lenging. A literature review across multiple
countries published by Fulton and Allen (2005)
identified the incidence of polypharmacy in the
The Encyclopedia of Adulthood and Aging, First Edition. Edited by Susan Krauss Whitbourne.
© 2016 John Wiley & Sons, Inc. Published 2016 by John Wiley & Sons, Inc.
DOI: 10.1002/9781118528921.wbeaa311
elderly to range from 5% to 78%.
the prevalence of polypharmacy we can look
at both studies describing medication use and
studies specifically looking at occurrences of
polypharmacy or unnecessary medication use.
Several studies have evaluated polyphar-
macy in the outpatient setting. Qato et al.
(2008) reported that 29% of a sample of 2,976
community-residing adults aged 57 to 85
reported taking at least five prescription med-
ications. Bushardt, Massey, Simpson, Ariail,
and Simpson (2008) applied two definitions
to evaluate polypharmacy in 1,270 outpa-
tients aged 65 and older: use of six or more
concurrent drugs and use of a potentially
inappropriate drug. In this study, 29.4% of
patients evaluated were prescribed six or more
concomitant drugs and 15.7% were prescribed
at least one potentially inappropriate drug,
whereas 9.3% of patients met both definitions
used. Approximately 60% of a cohort of 3,070
ambulatory patients aged 75 and older enrolled
in the Ginkgo Evaluation of Memory Study
were found to be taking at least three pre-
scription medications. The mean number (±
standard deviation [SD]) of prescription med-
ications and dietary supplements reported per
person were 3.5 (±2.7) and 3.4 (±3.0; Nahin
et al., 2009). Husson et al. (2014) completed a
cross-sectional study to identify the prevalence
and factors associated with polypharmacy in
community-dwelling adults aged 60 and older.
Of a sample of 2,545 participants, 30% pre-
sented with polypharmacy defined as four or
more medications. The mean (± SD) number
of medications per person in the polypharmacy
group was 5.67 (±1.82) medications.
Fewer studies have evaluated the preva-
lence of polypharmacy in the hospital setting
(Nobili et al., 2011). A study looking at 384
frail patients aged 65 and older at hospital
discharge identified 41.4% to be taking five
to eight medications, 37.2% to be taking nine
or more medications, and 21.4% to be taking
2 POLYPHARMACY
one to four medications. Using the Medication
Appropriateness Index, the investigators con-
cluded that 44% of the participants were taking
at least one unnecessary medication (Hajjar
et al., 2005). The REPOSI study examined
polypharmacy in hospitalized patients aged
65 and older both at admission and at dis-
charge. Polypharmacy was defined as use of
five or more medications. On admission these
researchers found the prevalence to be 51.9%
(n = 1,332) and at discharge they found the
prevalence to be 67% (n = 1,155; Nobili et al.,
2011).
Lastly, Beloosesky, Nenaydenko, Gross Nevo,
Adunsky, and Weiss (2013) published a recent
study on the prevalence of polypharmacy
in nursing home residents. They specifically
looked at the rate of polypharmacy in 993
residents aged 65 and older in six nursing
homes in Israel. They identified the mean
rate of polypharmacy, defined as greater than
five drugs, to be 42.6% and the mean rate of
polypharmacy defined as greater than seven
drugs to be 18.6%.
The Most Common Drugs
Specific classes of drugs have been identified
as those most commonly associated with
polypharmacy. Fulton and Allen (2005) identi-
fied cardiovascular, asthma, psychotropic, and
sedating drugs as classes that increase the risk
of polypharmacy. Acetaminophen, ibuprofen,
and aspirin were identified as over-the-counter
medications associated with increased risk of
polypharmacy. In the aforementioned study
by Qato et al. (2008), the most common med-
ications reported (>5% of participants) were
(in order of prevalence) aspirin, hydrochloro-
thiazide, atorvastatin, levothyroxine, lisinopril,
metoprolol, simvastatin, atenolol, amlodip-
ine, metformin, acetaminophen, furosemide,
and ezetimibe. The Kuopio 75+ Study con-
ducted in Finland looked at medication use in
home-dwelling patients aged 75 years or older.
The most commonly used drugs identified in
patients classified into a polypharmacy group
(defined as taking six to nine medications)
and an excessive polypharmacy group (defined
as taking 10 or more medications) were car-
diovascular drugs (most common subgroups:
nitrates, beta-adrenoreceptor antagonists, and
diuretics, in order of prevalence) and anal-
gesics (Jyrkkä, Enlund, Korhonen, Sulkava, &
Hartikainen, 2009).
Similarities can be seen in the drugs most
commonly identified in polypharmacy studies
between the studies conducted in the ambu-
latory care setting and those conducted in
the hospital and nursing home settings. The
study (Hajjar et al., 2005) described above
looking at frail patients aged 65 and older
at hospital discharge identified the most
commonly used unnecessary drug classes as
gastrointestinal, central nervous system, and
therapeutic nutrients and minerals. The most
common drugs were histamine-2 receptor
blockers, laxatives, genitourinary antispas-
modics, and tricyclic antidepressants (in order
of prevalence). The 10 most common drugs at
admission and discharge in the REPOSI study
were antithrombotic agents, drugs for peptic
ulcer and gastroesophageal reflux disease,
high-ceiling diuretics, angiotensin convert-
ing enzyme inhibitors, beta blockers, lipid
modifying agents, blood-glucose-lowering
drugs (excluding insulin), cardiac glyco-
sides, vasodilators used in cardiac disease,
and insulins and analogs (in order of preva-
lence; Nobili et al., 2011). Beloosesky et al.
(2013) found the drug classes most fre-
quently prescribed to nursing home patients
treated conditions associated with the gas-
trointestinal, nervous, and cardiovascular
systems.
Risk Factors
Numerous risk factors for polypharmacy have
been identified. Sociodemographic factors that
predispose a patient to polypharmacy include
increased age, female gender, white race, rural
residence, and low or medium education
level (Fillenbaum et al., 1996; Fulton & Allen,
2005; Hajjar, Cafiero, & Hanlon, 2007; Husson
et al., 2014; Jyrkka et al., 2009; Rollason &

Vogt, 2003). Health status factors can also be
examined to help determine the likelihood
of polypharmacy. Moderate or poor reported
health status, increased severity of chronic
disease, history of falls, increased number
of diagnoses, and number of adverse events
during hospital stay have all been associated
with polypharmacy (Fillenbaum et al., 1996;
Jyrkka et al., 2009; Husson et al., 2014; Nobili
et al., 2011; Tamura, Bell, Inaba, & Masaki,
2012). Many specific disease states have also
been implicated, including anemia, angina,
anxiety, asthma, atrial fibrillation, cardiovas-
cular disease, chronic obstructive pulmonary
disease, chronic renal failure, depression,
diabetes mellitus, diverticulosis, gout, heart
failure, hypertension, ischemic heart disease,
metabolic syndrome, osteoarthritis, osteoporo-
sis, pain, stomach disorders, and stroke (Fulton
& Allen, 2005; Hajjar et al., 2007; Jyrkka et al.,
2009; Nobili et al., 2011; Tamura et al., 2012).
Additionally, access to healthcare is involved
in the prevalence of polypharmacy. Patients
with increased numbers of healthcare vis-
its, multiple providers, multiple pharmacies,
supplemental insurance, and prescription
insurance coverage are at an increased risk
for polypharmacy (Fillenbaum et al., 1996;
Fulton & Allen, 2005; Hajjar et al., 2007;
Husson et al., 2014; Rollason & Vogt, 2003;
Tamura et al., 2012). Lastly, medication factors
may also increase the risk of polypharmacy,
including using nine or more medications,
using medication without an indication, the
extent of previous medication use, purchasing
over-the-counter medications, and borrowing
medications from family and friends (Fillen-
baum et al., 1996; Fulton & Allen, 2005; Hajjar
et al., 2005; Rollason & Vogt, 2003).
Consequences of Polypharmacy
Consequences of polypharmacy include
increased drug costs, adverse drug reactions
(ADRs), drug interactions, nonadherence,
diminished functional status, and various
geriatric syndromes.
POLYPHARMACY 3
Adverse Drug Reactions
In the United States in 2005, there were an
estimated 4.3 million ADR-related health-
care visits (Bourgeois, Shannon, Valim, &
Mandl, 2010). Significant risk factors for the
ADR-related visits included age greater than 65
years and polypharmacy. Not only have ADRs
been noted to occur in 35% of outpatients and
44% of hospitalized elderly patients (Rollason
& Vogt, 2003) but ADRs have also been shown
to account for approximately 10% of emergency
room visits (Hohl, Dankoff, Colacone, & Afi-
lalo, 2011). In Canada, although only 0.75% of
emergency department visits were due to ADRs
in older adults, 20% of those patients were then
hospitalized (Wu, Bell, & Wodchis, 2012). The
risk of ADRs has been associated with the
number of medications, with a prevalence of
58% with five medications and increasing even
further to 82% with seven or more medica-
tions (Prybys, Melville, Hanna, Gee, & Chyka,
2002). Healthcare providers should be aware
that common drug classes associated with
ADRs are antibiotics, anticoagulants, cardio-
vascular drugs, diuretics, hypoglycemic, and
nonsteroidal anti-inflammatory drugs (Hohl
et al., 2011).
Drug Interactions
Drug–drug interactions (DDIs) are a con-
cern in older adults due to polypharmacy,
nutritional status, and multiple comorbidities,
which have the potential to alter pharma-
cokinetic and pharmacodynamic properties
of medications (Mallet, Spinewine, & Huang,
2007). Prevalence of potential DDIs has been
reported to be between 35% and 60% in elderly
patients (Rollason & Vogt, 2003). As one might
expect, the potential for DDIs is associated
with number of medications and is estimated
to be almost 100% with the use of eight or
more medications (Sloan, 1983). There is an
association between DDIs and preventable
ADRs and hospitalizations related to drug
toxicity in older adults (Juurlink, Mamdani,
Kopp, Laupacis, & Redelmeier, 2003).
A wide range (15–40%) in the prevalence of
drug–disease interactions has been reported
4 POLYPHARMACY
for older adults (Lindblad et al., 2005, 2006;
Pugh et al., 2011). Number of drug and
comorbidities has been associated with risk
of drug–disease interactions (Lindblad et al.,
2005). Since most patients suffer from multiple
conditions, drug–disease interactions are a
concern.
Nonadherence
Nonadherence has been associated with
polypharmacy (Hajjar et al., 2007). Medica-
tion adherence rates in community-dwelling
older adults are varied and have reported to
be between 43% and 95% (Vik, Maxwell, &
Hogan, 2004). Reasons for variability are gen-
erally attributed to the various definitions of
medication adherence, population characteris-
tics, and tools. Polpharmacy has been reported
to be a strong predictor of nonadherence
(Colley & Lucas, 1993; Salazar, Poon, & Nair,
2007). Disease progression, treatment failure,
and hospitalizations have been associated with
medication nonadherence (Salazar et al., 2007).
Other Consequences of Polypharmacy
Functional decline has been associated with the
use of multiple medications (Magaziner, Cadi-
gan, Fedder, & Hebel, 1989). A cross-sectional
study found that polypharmacy was associated
with diminished ability to perform instrumen-
tal activities of daily living (Crentsil, Ricks,
Xue, & Fried, 2010). Although medication may
be used to preserve some functional capacity,
providers should be aware of the association
between polypharmacy and functional decline.
Although the use of medications may
decrease certain healthcare costs, the con-
sequences of polypharmacy can increase
healthcare costs and geriatric syndromes. In
Canada, ADR-related emergency department
visits and hospitalizations in older adults
was estimated at C$35 million (Wu et al.,
2011). Another retrospective study reported
that approximately 9% of total drug-related
expenditure was on potentially inappropriate
medications (Cahir et al., 2010). Polypharmacy
has been associated with various geriatric
syndromes such as cognitive impairment,
falls, urinary incontinence, and decreased
nutritional status in older adults (Gorm-
ley, Griffiths, McCracken, & Harrison, 1993;
Hayes, Klein-Schwartz, & Barrueto, 2007;
Heuberger & Caudell, 2011; Jyrkka, Enlund,
Lavikainen, Sulkava, & Hartikainen, 2010;
Kojima et al., 2011; Leipzig, Cumming, &
Tinetti, 1999a, 1999b).
Clinical Approaches to Improving
Polypharmacy
Drug Regimen Reviews
Drug regimen reviews have been shown to
reduce polypharmacy regardless of setting
(Fick et al., 2004; Fillit et al., 1999; Galt, 1998;
Hanlon et al., 1996; Muir, Sanders, Wilkin-
son, & Schmader, 2004; Schmader et al.,
2004; Zarowitz, Stebelsky, Muma, Romain,
& Peterson, 2005). The first step to reduc-
ing polypharmacy is collecting a detailed
medication history for both prescription
and over-the-counter medications at each
health-related encounter. Patients should
either bring in all medications or bring a list
with them to each healthcare visit to ensure
that all those involved in their care know what
they are taking.
After a thorough medication history has been
taken, providers should determine whether
each medication is needed and whether the
medication’s benefit outweighs its risks. Each
medication should match an indication from
the patient’s medical history. If a medication
does not have an indication, providers should
evaluate whether that medication is needed.
Although some medications may be abruptly
discontinued, some may need to be tapered off
to prevent an adverse drug withdrawal event.
Medication may also be added to regimens
to control the side effects of other medica-
tions. If that is the case, those medications
should be evaluated to see whether the med-
ication regimen can be simplified to avoid
a prescribing cascade. Existing medications
should also be reviewed at each encounter
to continually determine their usefulness or
whether modification is needed as the health

status of patients is known to change over
time. For medications that are needed for
treatment, providers need to continually eval-
uate the medication’s pharmacokinetic and
pharmacodynamic properties, the medication’s
side-effect profile, and the patient’s current
hepatic and renal function for accurate dosing.
Other considerations for medication man-
agement include cost, patient preference, and
potential for drug–drug and drug–disease
interactions. Patient and providers should also
agree on therapeutic goals and monitoring
parameters that will help to guide therapy.
Improved adherence may be improved by
providing simplified medication regimens and
educating patients and caregivers about each
medication regimen (Schrader et al., 1996).
The SAIL and TIDE techniques may also
be helpful in remembering ways to reduce
polypharmacy. The former refers to:
Simple: Simplicity is best for medication regi-
mens.
Adverse effects: Be aware of the potential
adverse effects of medications and those
medications that are used to treat the
adverse effects of other medications.
Indication: Each medication should have an
indication.
List: The medical chart and patient should have
an accurate medication list at all times.
And the latter refers to:
Time: Time is needed to discuss medica-
tion-related issues at each medical encounter.
Individualize: Individualized therapy requires
the application of pharmacokinetic and
pharmacodynamic principles.
Drug–drug and drug–disease interactions:
Potential drug–drug and drug–disease
interactions need to be considered.
Educate: Patient and caregiver education is
important to reduce polypharmacy. Edu-
cation should include expected medication
effects, potential adverse effects and DDIs,
and monitoring parameters.
POLYPHARMACY 5
Conclusions
Polypharmacy in older adults is associated
with significant consequences, such as adverse
effects, medication nonadherence, drug–drug
and drug–disease interactions, and increased
risk of geriatric syndromes. Every health-
care encounter is an opportunity to review
all existing medications for appropriate-
ness, risks and benefits, and potential for
consequences.
SEE ALSO: Alcohol and Illicit Drug Use; Care Plan-
ning in Frailty; Comorbidity; Delirium; Falls
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POLYPHARMACY 7
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