E.R. Hajjar et al.

The American Journal of Geriatric Pharmacotherapy

Polypharmacy in Elderly Patients
Emily R. Hajjar, PharmD, BCPS, CGPI; Angela C. Cafiero, PharmD, CGp2; and
Joseph T. Hanlon, PharmD, MS, BCPS 3-s
I Philadelphia College o f Pharmacy, University o f the Sciences in Philadelphia, Philadelphia, Pennsylvania; 2Abbott Laboratories,
Abbott Parl~ Illinois; 3Geriatric Research, Education and Clinical Center, Pittsburgh VAMC, Pittsburgh, Pennsylvania; 4Center for
Health Equity Research and Promotion, Pittsburgh VAMC, Pittsburgh, Pennsylvania; and 5Department o f Medicine (Geriatrics),
University o f Pittsburgh, Pittsburgh, Pennsylvania
ABSTRACT
Background: Polypharmacy (ie, the use of multiple medications and/ or the administration of more medications
than arc clinically indicated, representing unnecessary drug use) is common among the elderly.
Objective: The goal of this research was to provide a description of observational studies examining the epidemi-
ology of polypharmacy and to review randomized controlled studies that have been published in the past 2 decades
designed to reduce polypharmacy in older adults.
Methods: Materials for this review were gathered from a search of the MEDLINE database (1986-June 2007)
and International Pharmaceutical Abstracts (1986-June 2007) to identify articles in people aged >65 years. We used
a combination of the following search terms: polypharmacy, multiple medications, polymedicine, elderly, geriatric, and
aged. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and
recent reviews was conducted to identify additional articles. From these, the authors identified those studies that
measured polypharmacy.
Results: The literature review found that polypharmacy continues to increase and is a known risk factor for impor-
tant morbidity and mortality. There are few rigorously designed intervention studies that have been shown to reduce
unnecessary polypharmacy in older adults. The literature review identified 5 articles, which are included here. All
studies showed an improvement in polypharmacy.
Conclusions: Many studies have found that various numbers of medications are associated with negative health
outcomes, but more research is needed to further delineate the consequences associated with unnecessary drug use
in elderly patients. Health care professionals should be aware of the risks and fully evaluate all medications at each
patient visit to prevent polypharmacy from occurring. ( A mJ Geriatr Pharmacother. 2007;5:345-351) Copyright
2007 Excerpta Medica, Inc.
Key words: polypharmacy, older adults, morbidity, mortality.
Accepted for publication August 24, 200Z
Pr i nt ed in t he USA, Repr oduc t i on in wh o l e o r p a r t is n o t per mi t t ed,
doi:10,1016/j,amj ophar m, 2007, 12, 002
1543 5946/ $32, 00
Volume 5 Number 4 December 2007 Copyright 2007 Excerpta Medic& Inc. 345
The American Journal of Geriatric Pharmacotherapy E. R. Hajjar et al.
I N T R O D U C T I O N
People aged _>65 years are one of t he most rapidly
growi ng age groups in the Uni t ed States. In 2005,
there were - 27 million adults in this age group, wi t h
t he number of women out wei ghi ng men. 1 Many older
adults have multiple medical conditions, such as hyper-
tension, arthritis, heart disease, cancer, and diabetes
mellitus, which require multiple medications for proper
t reat ment . 1,2 The use of multiple medications is often
referred t o as polypharmacy, but a st andard definition
is not used. 3 A second and perhaps more i mpor t ant
definition is t he administration of more medications
t han are clinically indicated, representing unnecessary
drug us e . 4 Unfort unat el y, using multiple medications
may cause probl ems such as t he increased risk of inap-
propriate use of medications (including dr ug- dr ug in-
teractions and duplication of therapy), nonadherence,
and adverse effects.
Thc objective of this review was to provide a descrip-
tion of observational studics cxamining thc cpidcmiology
of polypharmacy and to review randomi zed controlled
studies t hat have been published in the past 2 decades
dcsigncd to rcducc polypharmacy in oldcr adults.
MAT ERI AL S A N D M E T H O D S
The MEDLI NE database ( 1986- J une 2007) and
Int ernat i onal Pharmaceut i cal Abstracts ( 1986- J une
2007) were searched to identify articles on polyphar-
macy in t he elderly. We used a combi nat i on of t he fol-
lowing search terms: polypharmacy, multiple medica-
tions, polymedicine, elderly, geriatric, and aged. We also
conduct ed a manual search of the reference lists from
identified articles and t he aut hors' article files, book
chapters, and recent reviews to i dent i fy additional
articles.2 13 Articles were i ncl uded onl y if t hey were:
(1) in English; (2) involved t hose aged >65 years;
(3) not a review; or (4) observational or r andomi zed
trials t hat either quantified t he multiple use of medi-
cines and their consequences or described i nt ervent i ons
to reduce polypharmacy.
RESULTS
Drug Uti l i zati on Studi es
Twent y-one studies were examined. There is not a
consistent cut poi nt t hat defines polypharmacy. Previous
studies have used 2, 4, 5, and 9 medications to identify
polypharmacy, s,144 Surveys of communi t y-based elderly
patients show t hat 2 to 9 prescription medications on
average are taken per day. 5,7,21,22 A national survey by
Kaufman et a123 f ound t hat 57% of US women aged
_>65 years t ook _>5 prescription medications and 12%
t ook _>10 medications. This is consistent with results
from a large st udy in Europe (N = 2707; mean age,
82.2 years), which f ound t hat 51% of patients t ook
_>6 medications per day. 16
It is also i mport ant to evaluate the use of non-
prescription medications in older adults. A study of
1059 rural community-dwelling elderly patients (mean
age, 74.5 years) f ound t hat almost 90% t ook _>1 and
almost 50% t ook 2 to 4 over-the-counter medications. 24
Anot her study of 2590 noninstitutionalized patients
report ed t hat 47% to 59% of older patients t ook a vita-
min or mineral and 11% to 14% t ook herbal supple-
ments. 23 Data also suggest t hat polypharmacy may
be increasing in the elderly, especially in those aged
>85 years. 17
An i mpor t ant consideration in evaluating polyphar-
macy is the types of medications t hat are being con-
sumed. A large national survey in t he Uni t ed States
f ound t hat the most common prescription medications
used in noni nst i t ut i onal i zed patients were est rogen
product s, levothyroxine, hydrochl orot hi azi de, atorva-
statin, and lisinopril. 23 Cardiovascular agents, antibiot-
ics, diuretics, opioids, and antihyperlipidemics were t he
most frequent l y used classes of prescription medica-
tions in a large st udy of Medi care patients. 2s Pain
medications (eg, acet ami nophen, i buprofcn, ace@sali-
cylic acid), cold and cough medications (eg, pseu-
doephedri ne, di phenhydrami ne), and vitamin or nutri-
ent product s (eg, multivitamins, vitamins E and C,
ginseng, Ginkgo biloba extract) were t he most common
nonprescri pt i on medications consumed. 23 Analgesics,
vitamins, minerals, antacids, and laxatives were also
f ound to be commonl y used nonprescri pt i on agents
among t he elderly. 24
Preval ence, Predi ct ors, and Risks of
Unnecessary Pol yphar macy
Five studies have evaluated the unnecessary drug use
definition ofpol ypharmacy. 26 30 A study of 236 ambula-
t or y patients aged _>65 years by Li pt on et a126 f ound t hat
almost 60% of patients were taking medications t hat
were suboptimal or lacking an indication. Schmader et
a127 had similar findings: t hey report ed t hat 55% of
208 elderly patients were taking drugs wi t hout an indi-
cation. They also f ound t hat one t hi rd of patients were
taking ineffective drugs, and 16% had a therapeutic
duplication in their medication regimens. In a st udy of
834 outpatients aged _>65 years, Schmader et a128 evalu-
at ed unnecessary drug use, defined by the Medi cat i on
Appropriateness Index (MAI) criteria as a medi cat i on
with no indication, lack of effectiveness, or therapeutic
346
E.R. Haj j ar et al. The Ameri can Journal of Geriatric Pharmacotherapy
duplication. The daily mean number of unnecessary
drugs was 0.65 per person. A study in frail elderly veter-
ans (N = 384), which also used the MAI to define
unnecessary drug use, found that 44% of patients had
_>1 unnecessary medication at hospital discharge, with
25% of the patients having the medication started dur-
ing the hospitalization. 29 The reasons for the unneces-
sary drug use included no indication (32%), lack of
effcctiveness (18%), and therapeutic duplication (7%).
Gastrointestinal, central nervous system, and therapeutic
nutrient/mineral agents were found to be the most
commonly used unnecessary drugs. Another recent
study 3 of veteran outpatients (N = 196) aged _>65 years
found a 64% prevalence of medication underuse. This
study also showed that underuse and unnecessary use of
medications simultaneously occurred in 42% of patients.
No studies were found in the literature search linking
unnecessary drug use with health outcomes. However, it
is likely that unnecessary drug use would be related to
increased drug expenditures.
Risk Factors for Polypharmacy
Ninc studics wcrc asscsscd to dctcrminc thc risk factors
for polypharmacy. Many risk factors for polypharmacy
havc bccn idcntificd and can bc classificd into 1 of
3 groups: dcmographic, hcalth status, and acccss to
hcalth carc charactcristics. Incrcascd agc, whitc racc,
and cducation arc dcmographic charactcristics associ-
atcd with polypharmacy. 17,21,31,32 Poorcr hcalth, dcprcs-
sion, hypcrtcnsion, ancmia, asthma, angina, divcrticu-
losis, ostcoarthritis, gout, diabctcs mcllitus, and usc of
_>9 mcdications arc thc hcalth status charactcristics
associatcd with polypharmacyfi ,14,29,31 33 Prcdictors of
polypharmacy rclatcd to acccss to hcalth carc charactcr-
istics includc numbcr of hcalth carc visits, supplcmcntal
insurancc, and multiplc providcrs. 32 34
Consequences of Polypharmacy
Eighteen studies examined the consequences associ-
ated with polypharmacy. There may be many conse-
quences associated with polypharmacy. Patients are at
an increased risk of receiving an inappropriate medica-
tion and having an adverse drug reaction (ADR), which
may impact a patient's adherence to his or her medica-
tion regimen. Polypharmacy has also been reported to
increase the risk of geriatric syndromes and morbidity/
mortality.
Adherence
Polypharmacy creates complex medication regimens
that make nonadherence a common problem in the
elderly, with prevalence rates averaging 50%. 3S 37
However, elderly patients are adherent with -3 out of
every 4 of their individual medications. 3S,36 The elderly
also have adherence rates similar to younger patients
when number of drugs is taken into account. 38
Inappropri ate P rescribing
Studies have shown that the use of multiple medica-
tions increases the risk of inappropriate prescribing.
Hanlon et a139 found that both the number of prescrip-
tion (odds ratio [OR], 1.28; 95% CI, 1.21-1.36) and
nonprescription (OR, 1.17; 95% CI, 1.12-2.35) medi-
cations increased the risk of inappropriate prescribing
as defined by the MAI in frail elderly veterans. A cross-
sectional study in 786 patients (mean age, 78 years)
receiving home health care reported that polypharmacy
increased the risk of potentially inappropriate medica-
tions, as defined by the Beers criteria, and the risk of
potentially dangerous drug interactions. Is
Adverse Drug Reacti ons
The risk of ADRS may increase with increased num-
ber of drugs taken. An ADR, as defined by the World
Health Organization, is a reaction that is noxious and
unintended, and which occurs at dosages normally used
in humans for prophylaxis, diagnosis, or therapy. 4
ADRS have been reported to occur in 5% to 35% of
outpatients and account for as many as 12% of hospital
admissions in older patients. 6,25,41 43 The risk of ADRS
is strongly associated with multiple comorbidities, use
of specific types of drugs such as warfarin, and increas-
ing number of drugs taken. 3,6,18,41 45
Geriatric Syndromes
A study by Larson et a146 showed an increased risk of
cognitive impairment with multiple medications. A
study by Ruby et a147 found that the use of multiple
medications with urologic activity increased the risk of
urinary incontinence.
A few studies have examined the impact of multiple
medication use on falls. Those patients taking >2 psy-
chotropic agents had a 2.4- to 4.5-fold increased risk
of falling than those taking 1 central nervous system
drug. 48 A study by Agostini et a149 examined the risk of
polypharmacy and balance in 885 community-dwelling
residents aged >72 years. For impaired balance, adjusted
ORs were 1.44 (95% CI, 0.94-2.19) for those taking
1 to 2 medications, 1.72 (95% CI, 1.09-2.71) for those
taking 3 to 4 medications, and 1.80 (95% CI, 1.02-
3.19) for those taking >5 medications. The authors
concluded that a greater number of medications were
347
The American Journal of Geriatric Pharmacotherapy E.R. Haj j ar et al.
associated wi t h an increased risk of adverse dr ug out -
comes. 49 Wci ner et al So f ound t hat elderly male out -
pat i ent s ( N = 305; age range, 70- 104 years) taking
>2 central ner vous system medi cat i ons (ie, benzodi aze-
pines, ot her sedat i ve/ hypnot i cs, antidepressants, anti-
psychotics, opi oi d analgesics) had a 2. 37- f ol d increased
risk of falls.
Morbidity~Mortality
Ther e are data whi ch suggest t hat , even after con-
trolling for mul t i pl e comorbi di t i es, pol yphar macy is
associated wi t h a decline in physical and i nst rument al
activities of daily living. $1 Pol yphar macy is also associ-
at ed wi t h negative consequences, such as increased risk
of mortality. $2 In addi t i on, pol yphar macy increases
medical costs. Ol der pat i ent s wi t h hear t failure taking
11 doses per day were f ound t o have annual dr ug costs
>83800 in 2001. $3
I n t e r v e n t i o n s t o R e d u c e P o l y p h a r m a c y
Five studies were f ound t hat met our inclusion crite-
ria (Table).2,28,s4 $6 Overall, 3 studies were conduct ed
in managed care popul at i ons t hat used pr e s c r i be r edu-
cation as t he i nt er vent i on t o r educe p ol ypharmacy5 ,S4,SS
Anot her st udy ut i l i zed a medi cat i on grid t o alert pro-
viders as t o how many drugs were bei ng admi ni st ered. $6
Finally, t he last st udy was a r andomi zed cont r ol l ed trial
t hat eval uat ed t he use of geriatric evaluation and man-
agement ( GEM) on i npat i ent and out pat i ent care58
Al t hough t her e are a number of studies t hat have
t ar get ed ol der pat i ent s taking multiple medi cat i ons,
pol yphar macy may not be r educed i f one i mproves
bot h unnecessary use and under use simultaneously, as
no di fference in overall medi cat i ons will be f ound. 11
Several studies have pr oposed possible met hods of
r educi ng t he number of medi cat i ons for elderly patients.
Mui r et a156 supplied a medi cat i on grid t o medical resi-
Table. Summary of studies on reducing polypharmacy in ol der adults (ie, t hose aged >65 years).
Author/Year Setting Intervention Results
Muir et al, 2004 s6
Fillit et al, 1999 s4
Fick et al, 2004 ss
Zarowi t z et al, 20052
Schmader et al, 20042s
General medicine inpatient service
Medicare managed care organization
Medicare + Choice southeastern
managed care organization
Outpatient, managed care
Inpatient and outpati ent care
f or veterans
Medication grid provided t o
admitting residents that
listed all medications and
administration times f or
I week,
Mailing t o elderly Medicare
managed care members at risk
f or polypharmacy urging them
t o meet wi th thei r physicians
and bring medications wi th
them f or review,
Physicians were mailed a list
of patients taking potentially
inappropriate medications,
Clinical pharmacy medication
revi ew wi th physician education,
Inpatient or outpati ent GEM,
Medication grid reduced number
of medications per patient in
the intervention group (0,92)
compared wi th the control group
d,65) (P < O,OOI),
Off the 42% ofi the population at
risk who had a medication review
wi th thei r physician, 20%
report ed having a medication
discontinued,
Overall, 12,5% of potentially
inappropriate medications were
discontinued,
Overall, polypharmacy event rate
decreased from 29,01 t o
9,43 events/1000 patients after
the first mailing and from 27,99 t o
17,07 events/1000 patients after
the second mailing,
Unnecessary and inappropriate
drug use was reduced in
inpatients receiving GEM care
(P < 0,05),
GEM geriatric evaluation and management.
348
E.R. Hajjar et al. The American Journal of Geriatric Pharmacotherapy
dent s caring for hospi t al i zed elderly pat i ent s ready t o
be di scharged t o home t hat consisted of a listing of all
medi cat i ons and times of admi ni st rat i on over t he previ-
ous week. They f ound t hat t he number of medi cat i ons
was r educed in t he i nt er vent i on gr oup by 0. 92 per
pat i ent compar ed wi t h an increase of 1. 65 medi cat i ons
in t he cont r ol gr oup ( P < 0. 001) . Numbe r of doses per
day also decreased in t he i nt er vent i on gr oup. A survey
st udy in a Medi care managed care popul at i on eval uat ed
whet her a medi cat i on review by pr i mar y care physicians
resul t ed in a change in medi cat i ons. $4 Patients were
sent letters urgi ng t hem t o bri ng t hei r medi cat i ons in
for a review, and pr i mar y care physicians were given
clinical practice guidelines on pol ypharmacy. Of t he
42% of patients at risk who had a medi cat i on review
wi t h t hei r physician, 20% had a medi cat i on discontin-
ued by t hei r physician and al most 30% had a change in
medi cat i on dose. Anot her st udy among Medi care man-
aged care pat i ent s f ound t hat mailing physicians a list
of patients who were taking a pot ent i al l y i nappropri at e
medi cat i on resul t ed in a di scont i nuat i on of a medica-
t i on in 12.5% of cases. SS Zar owi t z et al 2 used clinical
pharmacists t o educat e and aid physicians in reduci ng
pol yphar macy among out pat i ent managed care pa-
tients ( N = 195, 971) . They f ound t hat t he rate of
pat i ent s receiving >5 medi cat i ons decreased f r om 7. 99
t o 4.1 e ve nt s / 1000 pat i ent s after t he i nt ervent i on. I t
was also r epor t ed t hat t he rate of overall pol yphar macy
event s- - def i ned as use of >5 medi cat i ons, >2 narcotics,
>2 benzodi azepi nes, >3 oral ant i di abet i c medi cat i ons,
or t he use of sildenafil wi t h a ni t r at e- - was r educed
f r om 27. 99 t o 17. 07 e ve nt s / 1000 patients after a sec-
ond mailing. 2
Onl y one st udy was f ound in our literature search
t hat at t empt ed t o r educe unnecessary dr ug use. A mul-
tisite, r andomi zed cont r ol l ed st udy was r epor t ed t hat
exami ned t he i mpact of i npat i ent and out pat i ent GEM
on dr ug- r el at ed pr obl ems in 834 patients at 11 US
Veterans Affairs hospitals and clinics. 2s They f ound t hat
i npat i ent GEM care significantly r educed ( P < 0. 05)
unnecessary dr ug use, as measur ed by t he MM, com-
par ed wi t h usual care.
Cl i ni cal Consi der at i ons f or Pol y pha r ma c y
Obt ai ni ng a t hor ough medi cat i on hi st or y is ver y
i mpor t ant before any new medi cat i on is prescri bed.
Bot h prescri pt i on and nonpr escr i pt i on medi cat i ons
need t o be t aken i nt o account and shoul d be br ought
wi t h t he pat i ent t o all heal t h care provi der visits. Once
t he prescri ber has a compl et e medi cat i on history, he or
she can t hen deci de whet her t he addi t i on of anot her
medi cat i on is clinically i ndi cat ed and i f t he benefits
out wei gh t he risk of use. Nonphar macol ogi c therapy,
such as diet modi fi cat i on or exercise, may be appropri -
ate instead of medi cat i on in some cases. I r a medi cat i on
is det er mi ned t o be clinically necessary, t he dr ug' s
pharmacoki net i c, phar macodynami c, and adverse-event
profile, al ong wi t h t he pat i ent ' s renal and hepat i c func-
t i on, must be t aken i nt o account for pr oper dosing.
St art i ng doses are oft en l ower in t he elderly and may be
admi ni st ered di fferent l y t han in younger pat i ent s t o
pr event t oxi ci t y f r om occurri ng. Ot her concomi t ant
disease states and medi cat i ons shoul d be evaluated t o
pr event any drug-di sease or dr ug- dr ug i nt eract i ons
f r om occurri ng. Educat i ng bot h pat i ent s and t hei r
families verbally and in writing about t hei r medi cat i ons
can i mprove adherence. Consi deri ng generi c opt i ons,
utilizing compl i ance aids (eg, pillboxes, medi cat i on
calendars), limiting t he prescribing of as-needed drugs,
simplifying medi cat i on regi mens t o medi cat i ons t hat
can be dosed QD or BI D, and encouragi ng family
suppor t may help enhance medi cat i on adherence. $7 59
Set t i ng sensible t herapeut i c goals and assessing medica-
t i on regi mens periodically are also ver y i mpor t ant t o
ensure t hat pol yphar macy does not lead t o unnecessary
medical probl ems.
C O N C L U S I O N S
Pol yphar macy is c ommon among t he elderly. Many
studies have f ound t hat various number s of medi cat i ons
are associated wi t h negative health out comes, but mor e
research is needed t o f ur t her del i neat e t he conse-
quences associated wi t h unnecessary dr ug use. Heal t h
care professionals shoul d be aware of t he risks and fully
evaluate all medi cat i ons at each pat i ent visit t o pr event
pol yphar macy f r om occurri ng.
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Addr ess cor r espondence to: Joseph T. Hanl on, PharmD, MS, BCPS, Depart ment of Medicine (Geriatrics),
University of Pittsburgh, Kaufman Medical Building, Suite 514, 3471 5th Avenue, Pittsburgh, PA 15213. E-mail:
hanlonj@dom.pitt.cdu
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