CHAPTER 104
Joseph T. Hanlon
Geriatric Pharmacotherapy
and Polypharmacy
INTRODUCTION
Medications are the most frequently used and misused form
of therapy for the medical problems of the aged. Geriatric
health care professionals and their patients rely heavily on
pharmacotherapy to palliate symptoms, improve functional
status and quality of life, cure or manage diseases, and poten-
tially prolong survival. There has been a major increase in
our knowledge about the epidemiology and the clinical
pharmacology of drugs in the elderly (see Chapter 23). This
chapter examines efficacy and safety problems (including
medication-related problems) of pharmacotherapy in aged
populations, measures to reduce medication-related prob-
lems including polypharmacy in the elderly, and principles
of optimal geriatric pharmacotherapy.
EFFICACY AND SAFETY
OF PHARMACOTHERAPY
FOR ELDERLY PATIENTS
The evidence for the efficacy of medication therapy in
elderly patients has been bolstered by a number of seminal
randomized controlled clinical trials for geriatric condi-
tions (e.g., behavioral complications with dementia) and
diseases (e.g., hypertension).1,2 Moreover, a number of new
and improved therapeutic medication entities have come to
market and improved the ability of health care profession-
als to treat certain conditions (e.g., cholinesterase inhibitors
for Alzheimer’s disease, α-blockers for prostatic hyperpla-
sia, and bisphosphonates for osteoporosis). In addition, the
future seems bright for further medication discoveries that
may benefit elderly people, as nearly 900 new medicines are
­currently in phase I to phase III testing.3
Despite these optimistic trends, there are still major limita-
tions in our knowledge regarding the efficacy and safety of
geriatric pharmacotherapy. Elderly patients are still under-
represented in premarketing clinical drug trials.4 Although
regulatory authorities have developed guidelines for pharma-
ceutical companies regarding new molecular entities that are
likely to have significant use in elderly patients, the full impact
of these guidelines has yet to be realized.5 In addition, those
trials that do include elders rarely include the “oldest-old” (i.e.,
85+), those with multiple comorbidities, or those taking mul-
tiple medications.4 These exclusions raise questions about the
generalizability of the results to frail elderly people. Moreover,
there is a paucity of postmarketing studies designed to com-
pare the effectiveness of two drugs in the treatment of common
conditions (e.g., duloxetine vs. gabapentin in management
of postherpetic neuralgia). In addition, formal postmarketing
surveillance of medications to determine adverse effects varies
from country to country, but usually it consists of case reports of
potential adverse effects—reports written by practitioners and
published in medical journals or spontaneous reports written
by practitioners, patients, or pharmaceutical companies and
submitted to regulatory agencies.6 These methods are limited
by underreporting and the lack of denominator information
880
Steven M. Handler
Robert L. Maher
Kenneth E. Schmader
about the population at risk. Thus, most safety information
must come from formal postmarketing observational studies
of specific therapeutic classes or conditions. This makes it dif-
ficult for prescribers to use evidence-based medicine to choose
the “best” drug therapy for their frail elderly patients. Hope-
fully these deficiencies in pre- and postmarketing evaluation of
efficacy and safety will be addressed in part by the Agency for
Healthcare Research and Quality (funded by the University
of Iowa), Older Adults Centers for Education and Research on
Therapeutics in the United States (see www.iowacert.org for
more details), and research utilizing national pharmacy dis-
pensing data such as the Medicare Part D claims data in the
United States (see http://www.cms.hhs.gov/PrescriptionDrug
CovGenIn/08_PartDData.asp for more details).
MEDICATION-RELATED PROBLEMS
IN ELDERLY PATIENTS
As mentioned previously, most information about
­medication-related problems must come from postmarketing
observational studies of specific therapeutic classes or condi-
tions. Problems commonly associated with medication use
include medication errors and medication-related adverse
events (Figure 104-1).7 Medication errors can be defined as “a
preventable event that may cause or lead to inappropriate med-
ication use or patient harm while the medication is in the con-
trol of the health care professional, patient, or consumer.”7–9
These errors can occur at various stages of the medication use
process—including the prescribing, order communication,
dispensing, administering, and monitoring stages.
Medication errors may result in three different types of
medication-related adverse patient events. The first type is
an adverse drug reaction (ADR), which is defined as
“a response to a drug that is noxious and
unintended and occurs at doses normally
used for the prophylaxis, diagnosis, or therapy
of disease, or for modification of physiologic
function,”10 pg. 289
The second is an adverse drug withdrawal event (ADWE),
defined as
“a clinical set of symptoms or signs that are
related to the removal of a drug,”6 pg. 30
The third is a therapeutic failure (TF), defined as
“a failure to accomplish the goals of treatment
resulting from inadequate drug therapy and not
related to the natural progression of disease
(e.g., omission of necessary medication therapy,
inadequate medication dose or duration, and
medication non-adherence),”11 pg. 1092
 Chapter 104  /  Geriatric Pharmacotherapy and Polypharmacy
MEDICATION USE PROCESS
Prescribing
Adverse drug
reactions
Order
communication
Dispensing
Therapeutic
Administering failures
Adverse
Monitoring drug
withdrawal
events
Medication-related
Medication errors
adverse patient events
Figure 104-1.  Conceptual model for medication-related problems in older
adults. (Adapted from Handler SM, Wright RM, Ruby CM, et al. Epidemiology of
medication-related adverse events in nursing homes. Am J Geriatr Pharmacother
2006;4:264–72.)
Medication-related patient adverse events were cited in
an Institute of Medicine report as a major patient-safety
concern in a variety of clinical settings including hospitals,
ambulatory care, and nursing homes.8 Two cost-of-illness
analyses done in the United States suggest that morbidity
and mortality associated with drug-related problems cost
an estimated $177.4 billion per year in ambulatory patients
and an estimated $4 billion per year in nursing home resi-
dents.12,13 Next we describe the ­epidemiology of these three
distinct medication-related adverse patient events.
EPIDEMIOLOGY OF ADVERSE DRUG
REACTIONS
Several authors have reviewed the epidemiology of
ADRs.6,7,14 Here we summarize some studies published
most recently. One of the worst adverse consequences of
pharmacotherapy is emergency department evaluation and
hospitalization. Budnitz et al evaluated the frequency and
characteristics of ADRs that lead to emergency department
visits in the United States over a 2-year period.15 Using
21,298 ADR case reports, the authors concluded that 5.9%
of all emergency department visits for adults over the age
of 65 were for ADRs. Yee et al conducted a retrospective
chart review of all older patients who visited the emergency
department and found that 12.6% of all encounters were
associated with an ADR.16 Pirmohamed et al conducted a
prospective evaluation of 18,820 patients who presented
to large general hospitals in England.17 The authors found
that 6.5% (1225) of emergency department evaluations
required hospital admission because of an ADR. The median
age of a patient admitted for an ADR was 76 years, and
the authors concluded that most ADRs were definitely or
possibly avoidable.
881
Few investigators have studied ADRs in elderly outpa-
tients or nursing home residents. In a large cohort study of
older ambulatory adults, 5.5% (1523 of 27,617) experienced
an ADR over a 12-month study period.18 Of those that
experienced an ADR, 27.6% (421) were considered pre-
ventable. In a group of 808 frail elderly outpatients, Hanlon
et al documented that 33% experienced an adverse drug
event over a 1-year follow-up period.19 Of those that
­experienced an ADR, 37.6% (187/497) were considered
preventable. Gurwitz et al studied the occurrence of ADRs
in 18 Massachusetts nursing homes.20 Over a 1-year period,
they found that 2916 nursing home residents had 546 ADRs,
an incidence rate of 1.89 ADRs per 100 ­resident-months.
Overall, nearly 44% of the ADRs were fatal, life threaten-
ing or serious, and 51% were preventable. In a more recent
study, Gurwitz et al examined the combined incidence of
ADRs in two academic nursing homes.21 In this 9-month
prospective observational study, 815 ADRs were detected
among 1247 nursing home residents, an incidence rate of
9.8 ADRs per 100 resident-months. As in their previous
study, Gurwitz et al found that the majority (80%) of ADRs
occurred at the monitoring stage of the medication-use pro-
cess and a large proportion (42%) were considered prevent-
able. Collectively, these studies from a variety of settings
document that ADRs are a common phenomenon in elderly
patients.
ADVERSE DRUG REACTION RISK
FACTORS
Investigators have attempted to identify a uniform set of
patient-level risk factors for the development of ADRs in
order to direct prevention efforts at high-risk individuals.15–21
Only four risk factors were uniformly found to increase the
likelihood of developing an ADR: presence of polypharmacy,
use of central nervous system agents, anti-infectives, and
anticoagulants. Multiple medication use or polypharmacy
is an important factor because it is potentially modifiable.
However, the reduction in number of medications in elderly
patients with multiple diseases may be difficult because the
diseases often require pharmacotherapy. It is also difficult to
avoid the drug classes most associated with ADRs, because
these drug classes are essential to the ­management of older
persons.
Investigators have suspected that age-related alterations
in pharmacokinetics and pharmacodynamics, fragmented
­medical care, suboptimal prescribing, suboptimal medica-
tion monitoring, and medication adherence influence the
risk of ADRs.22–30 The latter three items are clinically impor-
tant and will be discussed further in this chapter.
There are two major categories of suboptimal prescribing
that may contribute to ADRs: (1) overuse or polypharmacy
and (2) inappropriate use.26,27 Operational definitons of
polypharmacy differ by clinical setting. One common defin-
tion (9+ drugs) in U.S. nursing homes is found in nearly
60% of patients.31 There is limited information about poly-
pharmacy defined as the administration of more medications
than are clinically indicated.26,27 Two studies showed that
between 44% and 59% of outpatients were prescribed more
than one unnecessary drug.32,33
Inappropriate prescribing can be defined as prescrib-
ing a medication whose risks outweigh the benefits.26,27
882 Section III  /  Problem-Based Geriatric Medicine
A common medical standard that has been applied and stud-
ied in a variety of care settings has been the Beers explicit
criteria.34–36 Results of recent epidemiologic studies suggest
that the prevalence of prescribing a Beers criteria medication
is 12% in the ambulatory care setting, 29% in the hospital
setting, and 47% in the nursing home setting.37–39
Alternatively, inappropriate prescribing can be defined
as prescribing that does not agree with accepted ­medical
standards.26,27 Hanlon et al found that 91.9% of 365 elderly
ambulatory patients in the United States had one or more
prescribing problems as evaluated by the Medication Appro-
priateness Index (MAI).40 A study by Steinman et al found
in a sample of 170 older patients very little concordance
between those with polypharmacy (9+) drugs, or taking
an inappropriate drug as per the Beers criteria, or taking an
inappropriate drug as per the MAI.41 Of note, the MAI was
the most comprehensive approach, missing only 10% of
patients identified as having either polypharmacy or taking
a Beers criteria drug.41
Studies are starting to emerge describing problems asso-
ciated with suboptimal medication monitoring and its rela-
tionship to ADRs in a variety of care settings. For example,
two thirds of the ADRs experienced by older adults in the
emergency department were due to toxicity from a relatively
small set of drugs for which regular monitoring is commonly
required to prevent acute toxicity.15 In the ambulatory care
setting, a substantial proportion of older adults do not receive
appropriate laboratory monitoring while being prescribed
chronic medications, which also leads to an increased risk
of developing an ADR.28,29,42 Finally, as many as 70% of the
ADRs in nursing homes are related to a failure to appropri-
ately monitor medications.20,21
Medication adherence may also be a risk factor for ADRs.
However, the contribution of medication nonadherence to
ADRs is likely to be minor as elderly patients may be adher-
ent with up to 75% of their total number of medications
overall.30 Moreover, the most common type of medication
adherence problems is underuse.30
EPIDEMIOLOGY OF ADVERSE DRUG
WITHDRAWAL EVENTS
Adverse drug withdrawal events (ADWEs) are not for-
mally examined in premarketing clinical trials so one must
rely on clinical experience and published data in the post-
marketing period to glean information about these prob-
lems. The clinical manifestation of ADWEs may appear
either as a physiologic withdrawal reaction of the drug
(e.g., β-blocker withdrawal syndrome) or as an exacer-
bation of the underlying disease itself.43,44 There have
been few studies of this phenomenon in elderly patients.
Gerety et al investigated ADWEs in a single nursing home
in Texas over an 18-month time period and found that 62
nursing home patients experienced a total of 94 ADWEs
(mean 0.54 per patient), corresponding to an incidence
of 0.32 reactions per patient-month.45 Cardiovascular
(37%), central nervous system (22%), and gastrointesti-
nal drug classes were the most frequently associated with
an ADWE. Over 27% of ADWEs were rated as severe.
A study of ambulatory elderly patients by Graves et al in
the United States investigated ADWEs in 124 patients
and discovered that out of 238 drugs stopped, 62 (26%)
resulted in 72 ADWEs in 38 patients.46 Cardiovascular
(42%) and central nervous system (18%) drug classes
were the most frequently associated with an ADWE. In
26 of the ADWEs (36%), patients required hospitaliza-
tion, emergency room admission, or urgent care clinic
visits. Most of the ADWEs were exacerbations of an
underlying disease, and some withdrawal events occurred
up to 4 months after the medication was discontinued.
Finally, in a study by Kennedy et al, ADWEs were inves-
tigated in the postoperative period in a single hospital.47
Of 1025 patients studied, 50% were over the age of 60
years. Thirty-four patients suffered postsurgical compli-
cations resulting from drug therapy withdrawal. Specific
drug classes involved in ADWEs included antihyperten-
sives (especially ­angiotensin-converting-enzyme inhibi-
tors), antiparkinson medications (especially levodopa/
­carbidopa), benzodiazepines, and antidepressants.
ADVERSE DRUG WITHDRAWAL RISK
FACTORS
Little is known about the risk factors for ADWEs. In the
study by Gerety et al, ADWEs were associated with mul-
tiple diagnoses, multiple medications, longer nursing home
stays, and being hospitalized.45 Graves et al found that the
number of medications stopped was a significant predictor of
ADWEs.46 Analyses by Kennedy et al revealed that the risk
of an ADWE increased as the length of time off the medica-
tion increased.47
EPIDEMIOLOGY OF THERAPEUTIC
FAILURE
There have been few studies of this phenomenon in elderly
patients. In a U.S. study of therapeutic failure leading to
hospitalization, investigators used the reliable Therapeutic
Failure Questionnarie (TFQ) to measure therapeutic failure
in 106 frail older adults who were admitted to 11 Veterans
Affairs hospitals.48 Eleven percent of these individuals had
probable therapeutic failure leading to hospitalization. The
most common conditions associated with therapeutic fail-
ure involved congestive heart failure and chronic obstructive
pulmonary disease. In the emergency department, Ital-
ian investigators found that 6.8% of patients had evidence
of therapeutic failure with nearly two thirds occurring in
patients over the age of 65 years old.49 A U.S. investiga-
tion of drug-related emergency department visits in elderly
patients found that 28% of drug-related visits were due to
therapeutic failure.16
THERAPEUTIC FAILURE RISK FACTORS
Little is known about the risk factors for TFs. Reasons for ther-
apeutic failure may include low prescribed dose, drug-drug
interaction, drug resistance or nonresponse, inadequate thera-
peutic monitoring, nonadherence, or underprescrbing of nec-
essary drug therapy. We discuss the latter two reasons next.
Nonadherence was the most common reason for therapeu-
tic failure in the U.S. TFQ hospitalization study (58%) and in
the U.S. emergency department visit study (66%).16,48 Older
patients may not fill the prescription, not take a filled pre-
scription, skip doses, take the drug erratically, or reduce doses.
 Chapter 104  /  Geriatric Pharmacotherapy and Polypharmacy
These behaviors may be intentional (e.g., adverse effects,
health beliefs, concerns about taking too many drugs) or
unintentional (e.g., cognitive impairment, poor vision or dex-
terity, lack of transportation).50 Cost-related nonadherence is
a particularly important and prevalent subtype of intentional
nonadherence among older adults with limited means.51,52
Another major factor related to therapeutic failure is the
underprescribing of medications, which can be defined
as the omission of drug therapy that is indicated for the
­treatment or prevention of a disease or condition.26,27
A study that applied the explict Assessing Care of Vulner-
able Elders criteria found that 50% of 372 vulnerable adults
were not prescribed an indicated medication.42 The most
common problems were no gastroprotective agent for high-
risk nonsteroidal anti-inflammatory drug (NSAID) users, no
angiotensin-converting enzyme inhibitor (ACE-I) in dia-
betics with proteinuria, and no calcium or vitamin D for
those with osteoporosis.42 A group of U.S. investigators
using the Assessment of Underutilization of Medication
(AOU) measure found evidence of underuse of medications
in 62% of 384 frail elderly patients at hospital discharge.53
The necessary medication classes most likely to be omit-
ted were cardiovascular (e.g., antianginal), blood modifiers
(e.g., antiplatelet), vitamins (e.g., multivitamin), and central
nervous system (e.g., antidepressant) agents. Patients with
limited ability to perform basic activities of daily living and
greater comorbidity were at higher risk for undertreatment.
Clinical researchers have consistently detected underuse of
medications for specific diseases or conditions in older adults,
including congestive heart failure, myocardial infarction,
hypertension, hyperlipidemia, osteoporosis, depression, dia-
betes mellitus, and pain. For example, one study found that
only half of a large cohort of 21,138 elderly patients with
diabetes who also had hypertension or proteinuria received
recommended therapy with an angiotensin-converting
enzyme (ACE) inhibitor or angiotensin receptor blocker
(ARB) to retard progression of chronic kidney disease.54
MEASURES TO REDUCE MEDICATION-
RELATED PROBLEMS IN ELDERLY
PATIENTS
Given that medication-related problems are common,
costly, and clinically important, how can they be reduced?
The specific answer to this question is surprisingly difficult
because there are few health services intervention clinical
trials in elderly patients that examine measures to reduce
ADRs, ADWEs, or TFs. Therefore, health policy makers
and clinicians must look to reasonable, empirical approaches
that are based on existing epidemiologic and clinical infor-
mation. These approaches, to be discussed here, include
better health systems design, improved health services, and
patient/caregiver education. Health professional education
will be discussed in the last section on the principles of geri-
atric pharmacotherapy.
Health systems design
Medication-related problems can be reduced by designing
health care systems that make it difficult for individuals to do
the wrong thing and easy to do the right thing.55 In the latest
Institute of Medicine Report, Reducing Medication Errors, the
authors provide a number of specific recommendations to
883
improve medication safety.8 One recommendation is that all
health care organizations should immediately make complete
patient-information and decision-support tools available
to clinicians and patients. Another recommendation is that
health care systems should capture information on medica-
tion safety and use this information to improve safety. Health
care organizations should also implement the appropriate
systems to enable providers to have (1) access to compre-
hensive reference information concerning medications and
related health data, (2) assess the safety of medication use
through active monitoring and use these monitoring data
to inform the implementation of prevention strategies, (3)
write prescriptions electronically, and (4) subject prescrip-
tions to evidence-based, current clinical decision support.
A recent systematic review assessed the effects that comput-
erized physician order entry and clinical decision support
systems have on the quality, efficiency and cost of health
care for elders.56,57 These studies suggest that although the
amount of research available is limited, studies have been able
to demonstrate improvements in the quality and efficiency
of the medication use process. It is likely that the continued
development and refinement of clinical decision support sys-
tems will lead to a reduction in medication errors and medica-
tion-related adverse events in a variety of care settings.
Health services approaches
Four reviews summarize clinical trials where two health ser-
vices approaches, clinical pharmacist services and geriatric
medicine services, have shown an improvment in subop-
timal prescribing and medication adherence and reduced
ADRs in older adults.26,27,58,59 Clinical pharmacy is a health
science discipline that is concerned with the science and
practice of rational medication use. One study by Leape
et al showed that clinical pharmacist activities reduced
ADRs in intensive care unit patients.60 Geriatric medicine
services, also known as geriatric evaluation and manage-
ment (GEM), utilizes a multidisciplinary team of specialists
in geriatrics to manage patient care. The teams generally
consist of a geriatrician, physician, nurse, social worker
and pharmacist. An important component of GEM is the
assessment and optimal management of medications. One
study by Schmader et al showed that GEM care reduced
the risk of serious ADRs in frail outpatients.61 Additonal
large, multicenter controlled trials are needed to determine
the effectiveness of these and other approaches to optimiz-
ing medication use in older adults on medication-related
adverse patient events.
Patient/caregiver education
Systematic education of patients and caregivers about ADRs
may increase their ability to better report or avoid poten-
tial adverse drug events, thereby allowing clinicians to make
medication changes before these adverse events become
too serious. In addition, one study showed that when the
pharmacist counsels patients about their medications upon
hospital discharge, it can reduce the rate of adverse drug
reactions.62 One review summarized randomized controlled
trials designed to enhance medication adherence and related
outcomes in the elderly.63 Patient education and compliance
aids can improve medication adherence, which could poten-
tially reduce therapeutic failure that may lead to hospital-
ization because of a patient or caregiver’s decision to stop
884 Section III  /  Problem-Based Geriatric Medicine
a beneficial medication.63 Although not definitively shown,
it is sensible that patient and caregiver education about
ADWEs could prevent a patient or caregiver from stopping
a medication abruptly that should be withdrawn slowly.
PRINCIPLES OF GERIATRIC
PHARMACOTHERAPY
Clinicians who care for elderly patients need to know and
apply principles of geriatric pharmacotherapy in order to
maximize the benefits of medications in their elderly patients
and minimize medication-related problems (Table 104-1).
The first step in prescribing is to decide whether medica-
tion therapy is really necessary, as many medical problems
in elderly patients do not require a pharmacologic solution.
If the clinician decides that a medication is indicated and its
benefits outweigh its risks, then the choice of the medica-
tion must factor in the medication’s pharmacokinetics, the
patient’s renal and hepatic function, the medication’s main
potential adverse effects, and the patient’s other medica-
tions and diseases. The starting dose for most medications in
Table 104-1. Principles of Geriatric Pharmacotherapy
1. Consider whether medication therapy is necessary.
2. Know the pharmacology of the medication in relation to age.
3. Know the adverse effect profile of the medication in relation to
the patient’s other medication(s) and disease(s).
4. Choose initial dose, and adjust it carefully (doses will often need
to be smaller in elderly people).
5. Select the least costly alternative.
6. Establish clear, feasible therapeutic end points.
7. Monitor for adverse drug reactions, an important cause of
­geriatric illness.
8. Slowly taper medications to prevent/minimize adverse drug
withdrawal events (if possible).
9. Regularly review the need for chronic medications and
­discontinue unnecessary ones.
10. Assess whether there is omission of needed medication for the
established diagnosis/condition.
11. Review adherence, simplify the medication regimen, if possible,
and consider use of aids.
Table 104-2. Medications Associated With Adverse Drug Withdrawal Events in the Elderly
Medications Type of Withdrawal*
Alpha-antagonist antihypertensives
Angiotensin-converting enzyme inhibitors
Antianginal agents
Anticonvulsants
Antidepressants
Antiparkinson agents
Antipsychotics
Baclofen
Benzodiazepines
Beta-blockers
Corticosteroids
Digoxin
Diuretics
Histamine-2 blockers
Narcotic analgesics
Nonsteroidal anti-inflammatory drugs
Sedative/hypnotics (e.g., barbiturates)
*P, Physiologic withdrawal; D, exacerbation of underlying disease.
elderly patients must be lower, and the interval before modi-
fying the dosage often must be extended. Cost and establish-
ment of clear therapeutic end points are also important.
In the ongoing management of the patient and his or her
medications, the clinician should monitor for potential ADRs
via the history, physical examination, and, where appropri-
ate, laboratory data.6 The identification of ADRs can be a
challenging task in elderly patients because their ADRs may
present in a vague or atypical fashion and the causal link can
be difficult to establish. The first step is to consider ADRs in
the differential diagnosis of most geriatric syndromes. If the
adverse event is a known side effect of one or more of the
patient’s medications, the clinician can further enhance his
or her confidence in establishing ADR causality by consider-
ing the temporal relationship of onset of medication use to
onset of event, competing causes, rechallenge, dechallenge,
and other factors.64 Nonetheless, in some cases, the clinician
may find it difficult, and sometimes impossible, to establish
the ADR causal link between medication effect and illness in
elderly patients.
In patients who have recently stopped a medication, it is
important to consider the possibility of an ADWE. ADWEs
in elderly patients can be overlooked when the withdrawal
event is mistaken for a patient’s disease state. Common
events that may happen in the everyday care of an elderly
patient such as discontinuation of unwanted medications,
intentional noncompliance, stopping medications before a
surgical procedure, and managed care practices of medica-
tion substitution within classes of medications may lead to
an ADWE. Table 104-2 lists medications commonly used by
elderly patients that may be associated with withdrawal syn-
dromes or exacerbation of the underlying disease.43–46,65 To
prevent ADWEs, the clinician should take into account the
dose of the medication, the length of therapy of the medica-
tion, and the pharmacokinetics of the medication. Risk can
be minimized or eliminated by a slow, careful tapering of the
medication over a period of time. This approach is similar to
the time taken in the initiation and titration of a new medi-
cation. Unfortunately, precise tapering schedules have not
been established for most medications.
Withdrawal Syndrome
P Hypertension, palpitations, headache, agitation
P, D Hypertension, heart failure
D Myocardial ischemia
P, D Seizures
P, D Akathisia, anxiety, irritability, gastrointestinal distress, malaise, ­
myalgia, headache, coryza, chills, insomnia, recurrence of depression
P, D Rigidity, tremor, pulmonary embolism, psychosis, hypotension
P Nausea, restlessness, insomnia, dyskinesia
P Hallucinations, paranoia, insomnia, nightmares, mania, depression,
anxiety, agitation, confusion, seizures, hypertonia
P Agitation, confusion, delirium, seizures, insomnia
P Angina, myocardial infarction, anxiety, tachycardia, hypertension
P Weakness, anorexia, nausea, hypotension
D Heart failure, palpitations
D Hypertension, heart failure
D Recurrence of esophagitis and indigestion symptoms
P Restlessness, anxiety, anger, insomnia, chills, abdominal cramping,
diarrhea, diaphoresis
P Recurrence of arthritis and gout inflammatory symptoms
P Anxiety, muscle twitches, tremor, dizziness
 Chapter 104  /  Geriatric Pharmacotherapy and Polypharmacy
Table 104-3. Medication Appropriateness Index
Questions to Ask About Each Individual Medication
1. Is there an indication for the medication?
2. Is the medication effective for the condition?
3. Is the dosage correct?
4. Are the directions correct?
5. Are the directions practical?
6. Are there clinically significant drug-drug interactions?
7. Are there clinically significant drug-disease/condition interactions?
8. Is there unnecessary duplication with other medication(s)?
9. Is the duration of therapy acceptable?
10. Is this medication the least expensive alternative compared to
others of equal utility?
At every visit, it is necessary to review and, if possible, sim-
plify the patient’s medication regimen. This may be achieved
by altering the dosing schedule or discontinuing medicines
that are no longer needed. To conduct the review when
faced with an elderly patient taking multiple medications,
the clinician can utilize any of the standardized approaches
such as the Medication Appropriateness Index (MAI) (Table
104-3).66 The clinician should also consider whether nec-
essary medications have been omitted. A standardized tool
such as the Assessment of Underutilization of Medication
(AOU) can be used, which requires having a health profes-
sional match the complete list of chronic medical conditions
to the prescribed medications after reviewing the medical
record.67 In this manner, one can determine whether there
was an omission of a needed medication for an established
disease or condition based on the scientific literature. For
each condition, one of three ratings can be made: omission,
marginal omission (e.g., have used appropriate nonpharma-
cologic approach), or no omission.
The clinician should also consider providing adherence
aids for elderly patients. However, before providing the
patient with methods to enhance adherence, it is important
for the clinician to improve suboptimal prescribing and then
to talk to the patient about how he or she takes the medi-
cations so that an individualized plan can be developed. It
is also important to identify risk factors for poor adherence
(e.g., impaired hearing, vision, and cognition).30 Health care
professionals should also follow up with compliance rec-
ommendations by monitoring their patients. Some general
methods to enhance adherence in elderly patients include
simplifying regimens, providing written instructions, and
considering generic formulations to reduce costs. More spe-
cifically, pill boxes, increased font size on prescription labels,
calendars, easy-to-swallow dosage forms, pill cutters, oral
dosing syringes, insulin syringe magnification, tube spacer
for inhalers, and easy-open caps may increase adherence
in elderly patients. There are also some electronic devices
885
available as compliance aids (e.g., alarm watches with mes-
sages, automated pill delivery systems, medication bottles
with alarms) that may prove to be beneficial. Finally, active
patient and family involvement should be encouraged.
SUMMARY
Geriatric pharmacotherapy may greatly enhance the quality
of life of elderly patients by effectively palliating, prevent-
ing, or treating many diseases and conditions in late life. The
evidence for the efficacy of medications in elderly patients
has significantly increased over past decades thanks to some
clinical trials, and many more potentially beneficial medica-
tions are in development. However, clinical trial data may be
limited by the underrepresentation of older patients in many
trials, the exclusion of frail elderly or oldest-old patients, and
the lack of postmarketing studies designed to assess the effec-
tiveness of competing medications. In addition, the benefits
of medication therapy can be offset by ADRs, ADWEs, and
therapeutic failure. Although variable in their estimates of
the frequency of these medication-related problems, many
epidemiologic studies agree that these are common, costly,
and clinically important problems in elderly patients. Poten-
tial solutions to these problems include better health systems
design, health services approaches, and patient and caregiver
education. More research is needed to determine the feasi-
bility and effectiveness of these approaches. Clinicians who
care for elderly patients need to know and apply principles of
geriatric pharmacotherapy in order to maximize the benefits
of medications and minimize medication-related problems.
KEY POINTS
Geriatric Pharmacotherapy
and Polypharmacy
• There are limitations in our knowledge about the efficacy
and safety of medications in the elderly.
• Medication-related adverse patient events such as therapeutic ­failure,
adverse drug withdrawal reactions, and adverse drug reactions are
common and result in considerable morbidity in the elderly.
• Strategies to modify or reduce medication-related problems
including polypharmacy will require that health systems design/
institute new approaches to delivering care to elders.
• Clinicians should strive to conduct periodic systematic reviews
of elderly patients’ medication regimens as well as adhere to other
principles to optimize geriatric pharmacotherapy.
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