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P I
MONICA MATHYS and MYRA T. BELGERI
L O
1. Recognize the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for major
depressive disorder, anxiety disorders, and features commonly observed in late-life depression and anxiety.
2.
Recommend an appropriate treatment plan for a geriatric patient suffering from depression and/or anxiety.
3.
Recognize the changes in sleep that occur with normal aging and the impact of insomnia on an elderly patient’s
health and quality of life.
4.
Recommend appropriate therapy for insomnia based on published evidence in the elderly patient.
5. Describe the limitations of the DSM-5 criteria when used to diagnose elderly patients with substance-use
disorders.
6.
List the alcohol drinking limits for geriatric patients and discuss the reasons why guidelines suggest lower limits
compared to younger adults.
7. Recommend an appropriate treatment plan for alcohol withdrawal and long-term abstinence for a geriatric
patient.
13
K T D
CLINICAL GLOBAL IMPRESSION OF IMPROVEMENT (CGI-I): Seven-point scale that measures how much a
patient’s symptoms have improved or worsened compared to baseline.
COGNITIVE BEHAVIORAL THERAPY: Therapy to help patients correct negative thoughts associated with
depression and to cope with anxiety disorders. The therapy includes breathing retraining, muscle relaxation,
cognitive restructuring to focus on the consistent worrying, and graded exposure so the patient can learn how
to cope in stressful/phobic situations.
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| Fundamentals of Geriatric Pharmacotherapy
I
P
sychiatric disorders discussed in this chapter
include depression, anxiety, insomnia, and
substance abuse. Although diagnostic criteria
are the same as for younger adults for these
disorders, it is sometimes difficult to elicit clear
symptoms of depression or anxiety from older
patients, especially if they have underlying
dementia. Fortunately, newer pharmacologic
agents add options that are better tolerated in
individuals with comorbidities, multiple medica-
tions, and altered pharmacodynamics.
EARLY-ONSET ALCOHOLISM/ABUSE/DEPENDENCE: Alcohol abuse/dependence in which onset occurs before
the age of 50.
HAMILTON RATING SCALE FOR ANXIETY (HRSA): Fourteen-item assessment tool appropriate for measuring
symptom severity and treatment response for generalized anxiety disorder (GAD).
INTERPERSONAL PSYCHOTHERAPY: Therapy focused on finding and dealing with interpersonal causes of
depression.
LATE-LIFE ANXIETY: Anxiety episode that occurs when a patient is older.
LATE-LIFE DEPRESSION: Depressive episode that occurs when a patient is older.
LATE-LIFE SUBSTANCE USE DISORDER: Substance abuse or dependence in an older adult.
LATE-ONSET ALCOHOLISM/ABUSE/DEPENDENCE:
Alcohol abuse/dependence in which onset occurs at or
after the age of 50.
LATE-ONSET DEPRESSION: Major depression in which the first episode occurs when the patient is an older
adult. He or she has never had a depressive episode as a younger adult.
PARTIAL RESPONSE: A less than 50% reduction in symptoms.
PROBLEM-SOLVING THERAPY: Therapy that focuses on helping patients learn strategies for solving everyday
problems associated with their depression.
RECURRENCE: New episode of depression 6 months or longer after achieving remission.
RELAPSE: Increase in depressive symptoms within 6 months from remission.
REMISSION: An asymptomatic state.
RESPONSE: A 50% reduction in symptoms.
SLEEP EFFICIENCY: The amount of time asleep while in bed.
SLEEP RESTRICTION: Behavioral therapy that enhances the homeostatic drive for sleep by limiting the time
spent in bed to the time spent sleeping.
SUPPORTIVE THERAPY: Therapy that focuses on providing an environment in which patients can discuss and
be straightforward about their symptoms and causes of depression.
Sleep architecture and sleep physiology
change with aging; comorbidities and the envi-
ronment contribute to insomnia in the elderly
patient. If underlying factors cannot be corrected,
comorbidities are not treated and controlled,
and nonpharmacologic therapy is ineffective,
medications may help the patient achieve sleep
goals. However, it is important to choose drug
therapy that will minimize adverse events and for
the patient to understand how these agents work
to set proper expectations.
Finally, substance and alcohol use should
not be dismissed as a possible health issue
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in older adults. Alcohol withdrawal can be life-
threatening in any age group and is even more
of a risk for individuals with heart or lung disease.
Psychosocial interventions appropriate to older
age groups may be coupled with pharmacologic
treatment to maintain sobriety.
D
Etiology, Epidemiology, and
Clinical Presentation Specic to
Geriatrics
Depression is the most common psychiatric
disorder diagnosed in the elderly, with approxi-
mately 5% to 15% of community-based elderly
1-3
individuals meeting criteria for major depres-
sive disorder rising to 14% to 50% in the nursing
home population.
3,4
Often, a depressive episode
witnessed in older adults is a recurrence of the
disorder that was diagnosed as a young adult.
However, 30% of cases are noted to be purely
late-onset depression.
5
Common late-life diseases such as cerebral
vascular disease, cardiovascular disease, and
dementia often coexist or precipitate late-onset
depression.
6
For patients who have suffered a
stroke, major depression is noted to develop
in 15% to 25% of individuals.
7
Approximately
25% of patients who experience a myocardial
infarction or undergo cardiac catheterization
develop major depression.
8
The prevalence of
depression in patients with Alzheimer dementia
is approximately 10% to 20% and noted to be
higher in those with subcortical dementias.
9
Consequences of Late-Life Depression
If depression is left untreated, symptoms may
persist for years and result in decreased daily
function, poor quality of life, and increased rates
of suicide and nonsuicidal mortality.
10-16
One of
the more recent large epidemiologic studies
found that depressed elderly patients had a
significantly increased relative risk of 1.67 for
impairment of activities of daily living and 1.73 for
mobility impairment compared to nondepressed
elderly.
16
Over the last two decades, there have
been several studies showing a correlation
with depression and increased cardiovascular
mortality.
10,12,14,15
Research has repeatedly shown that
depression is associated with cognitive impair-
ment, but the relationship between the two is not
clear. Recent large studies have shown depres-
sion to be a risk factor for development of mild
cognitive impairment (relative risk of 2.35)
17
and
dementia (hazard ratio of 2.0),
18-20
with the risk of
vascular dementia being higher than the risk of
Alzheimer disease.
18,19
Studies have also shown
the risk of dementia increases with longer dura-
tion
19
and higher severity
20
of depressive symp-
toms. Even after multiple studies, it is still not
exactly clear whether depression is a definitive
risk factor for dementia later in life or if depres-
sion may be a prodromal symptom of dementia.
Diagnostic Criteria
Although many clinicians screen for depression
using the Geriatric Depression Scale or the other
tools discussed in Chapter 4, diagnosis is made
using criteria from the DSM-5.
21
A patient meets
the criteria for major depressive disorder if he
or she experiences either depressed mood or
decreased interest or pleasure in usual activi-
ties and meets at least four of the following
criteria: significant appetite and weight changes,
increased agitation or motor retardation, loss of
energy, changes in sleep (insomnia or hyper-
somnia), feelings of guilt or worthlessness, prob-
lems with memory or concentration, or thoughts
of suicide. According to the DSM-5, symptoms
must exist almost daily for at least 2 weeks, lead
to functional impairment, and not be the result of
substance abuse or other medical conditions.
21
Other mood disorders, such as persis-
tent depressive disorder (dysthymia) or minor
depression, are frequently assessed in the
geriatric population, and about 25% of these
cases will develop into major depression within
2 years.
6
Minor depressive disorder is not an offi-
cial DSM-5 disorder but has been defined in the
literature as having at least two but fewer than
five of the symptoms listed under major depres-
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| Fundamentals of Geriatric Pharmacotherapy
sive disorder for 2 weeks or longer. Persistent
depressive disorder is defined as a sad mood on
most days with two other symptoms listed under
major depressive disorder lasting for 2 years or
more. To meet the criteria for depressive disor-
ders, patients cannot have a history of mania or
psychotic disorders.
21
Assessment and Presentation
Noted risk factors for
late-life depression
include unmarried status, lack of social support,
lower socioeconomic status, family history of
mood disorders, substance abuse, experi-
encing a negative life event, prior depressive
episodes, history of cerebrovascular disease or
heart disease, chronic pain, and a diagnosis of
diabetes mellitus.
22,23
Other issues often coex-
isting with late-life depression include multiple
comorbidities, disability, and cognitive impair-
ment. Common social stressors of the elderly
may include loss of spouse, forced relocation
(e.g., being forced to move in with family or
assisted-living or nursing home placement), and
retirement, which may lead to decreased self-
worth, boredom, and loss of income.
6,24
Elderly depressed patients often complain
of decreased concentration and show defi-
cits in mental processing speed and execu-
tive function. These deficits often improve after
treatment of depression (and are sometimes
referred to as pseudodementia), but evidence
suggests mild cognitive dysfunction does not
always resolve completely.
6,25
In fact, individuals
who develop late-life depression and cognitive
impairment have a higher risk of developing
true dementia.
25,26
Compared to younger adults,
elderly patients with depression are less likely
to report crying spells, sadness, or feeling like
a failure. However, they are more likely to report
poor appetite, experience irritability and with-
drawal, and present to their health provider
complaining of somatic complaints, such as
vague aches and pains.
10,27
This can lead to
a delayed diagnosis and treatment, because
providers are often focused on treating the phys-
ical complaints of the patient.
KEY POINT:
ere is a correlation with
late-life depression and later-onset dementia.
However, it is still unclear whether depression
is a denitive risk factor for dementia or
a prodromal symptom of dementia.
Suicide Risk
Age is a major risk factor for suicide. Suicidal
ideation appears to occur more frequently in
younger adults, but completed suicides are
highest among older men.
24
The use of a firearm
is the most common method of death for elderly
suicide patients.
28
Risk factors for suicidal
behavior in older adults include a coexisting
psychiatric disorder especially anxious depres-
sion, substance abuse, a coexisting personality
disorder, chronic medical illness, poor coping
mechanisms, loneliness/isolation, and functional
impairment.
24,28,29
Data suggest antidepressant medica-
tions may increase the risk of suicidal ideation
in adolescents and young adults. However, this
risk has not been observed in older adults. In
fact, data suggest antidepressants may have a
protective effect against suicidal ideation in the
older population.
30
Summary of Standard Treatment in
the Adult Population
When depression is suspected, the duration
and severity of symptoms should be assessed
and a treatment history addressing current and
past therapies (nonpharmacologic and phar-
macologic) should be performed. A physical
examination, laboratory tests, and a thorough
medical history should be obtained in order to
assess whether medical conditions or medica-
tions may be worsening depressive symptoms
(Table 13-1).
31
Symptom remission rather than simply
response should be the optimal goal for clini-
cians and their patients. The large, multicenter
STAR-D (Sequenced Treatment Alternatives to
Relieve Depression) study showed patients who
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381
Table 13-1.
Medical Conditions and Medications Associated with Depression, Anxiety, and
Insomnia
6,29,73,75,123,133,134,219
Medical Conditions Medications
Depression
B12 deficiency
Cerebrovascular disease
Chronic pain
Diabetes mellitus
HIV/AIDS
Malignant disease
Malnutrition
Multiple sclerosis
Myocardial infarction
Parkinson disease
Thyroid disorders
Anticonvulsants
Benzodiazepines
Beta blockers
Cimetidine
Clonidine
Hydralazine
Opioid analgesics
Steroids
Tamoxifen
Anxiety
Angina
Arrhythmias
Chronic obstructive pulmonary disease
Heart failure
Hyperthyroidism
Parkinson disease
Pulmonary embolism
Stroke
Alcohol withdrawal
Anticholinergics
Antidepressants (initiation of therapy)
Benzodiazepine withdrawal
Caffeine
Steroids
Sympathomimetics
Theophylline
Thyroid hormones
Insomnia
Benign prostatic hyperplasia
Cardiovascular disease
Congestive heart failure
Chronic obstructive pulmonary disease
Chronic pain
Dementia
Depression
Malignancy
Parkinson disease
Restless leg syndrome
Sleep apnea
Stroke
Thyroid disease
Alcohol
Anticholinergics
Antidepressants
Antihistamines
Benzodiazepines
Beta agonists
Corticosteroids
Decongestants
Diuretics
Nicotine
Xanthines
achieved remission were more likely to have
increased daily function and less risk of relapse
in the long term compared to those who only
achieved a response with treatment.
32
Psychotherapy should be discussed as a
treatment option, and patients should also be
aware that it can often be used without drug
therapy for mild depression. According to recent
treatment guidelines,
31
any second-generation
antidepressant (selective serotonin reuptake
inhibitor [SSRI], serotonin–norepinephrine reup-
take inhibitor [SNRI], bupropion, or mirtazapine)
can be used as a first-line agent when drug treat-
ment is needed. If a response is seen after 4 to 6
weeks of therapy and the patient is tolerating the
medication, then therapy should be continued.
If only a partial response is observed, then the
current antidepressant dose should be increased
further or an additional agent added for augmen-
tation. Recommended agents for augmentation
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| Fundamentals of Geriatric Pharmacotherapy
include another second-generation antidepres-
sant that has a different mechanism of action,
thyroid hormone (T3 or T4), lithium, or a second-
generation antipsychotic. In cases where no
response is seen with the first-line agent, then
the patient should switch to another antidepres-
sant. When switching agents, cross-tapering is
recommended.
Using the results from the STAR-D study as
reference, clinicians can assume 30% of patients
are likely to achieve remission (~50% will have
a response) after taking one antidepressant for
12 weeks.
32
For patients who move on to a level
2 treatment (augmentation agent or switching
antidepressants), approximately 20% more will
obtain remission. For resistant patients, third- and
fourth-round treatments can be beneficial but
achieving remission continues to be difficult.
32
After remission has been achieved, treat-
ment should continue for at least 6–9 months.
Long-term therapy is recommended for patients
who have had multiple episodes of depression
in order to decrease the chance for recurrence.
31
Review of Evidence Supporting
Treatment Recommendations for
Geriatric Patients
Evidence-based treatment options for depression
in elderly patients also include psychotherapy
and antidepressant medications. Medications are
frequently prescribed in both the outpatient and
institutionalized setting. However, psychotherapy
has been shown to have equivalent efficacy
compared to antidepressants in older adults,
with 45% to 70% having clinical improvement.
33
Combination therapy (both psychotherapy and
antidepressant therapy) is most efficacious for
severe or chronic depression.
34,35
For mild depression, either psychotherapy
alone or medication therapy alone can be used
for treatment.
36
Methods of psychotherapy that
have shown clinical efficacy in late-life depres-
sion include cognitive behavioral therapy,
interpersonal psychotherapy, supportive
therapy, and problem-solving therapy.
36
Therapy is usually provided for at least 6 to
12 treatments and is highly recommended for
patients refusing pharmacologic treatment or for
those who have not responded or only partially
responded to drug therapy.
37
When depression is assessed as moderate,
medication treatment is strongly recommended,
with or without psychotherapy. Combination
therapy is recommended for severe or chronic
depression.
36
To date there have been several positive
studies supporting SSRI and SNRI therapy for
treatment of late-life depression.
38-48
The mean
age of patients in these studies ranged from 67
to 75 years, and rates ranged from 35% to 89%
for response and 31% to 72% for remission. These
agents appear to be as efficacious in the elderly
as first-generation agents, such as tricyclic anti-
depressants (TCAs),
29
but they are associated
with fewer adverse effects and are safer in over-
dose situations.
10,49,50
SSRI and SNRI antidepres-
sants, along with mirtazapine and bupropion,
are recommended as first-line agents for elderly
patients according to the most recent treatment
guidelines.
36
When initiating antidepressant treat-
ment, a low dose should be started but therapy
should continue to be titrated to a moderate dose
to receive an adequate response.
36
A recent
meta-analysis addressing antidepressant efficacy
showed medication response is most likely to be
observed after 10–12 weeks of therapy (versus 6
weeks in younger adults).
50
However, literature also
suggests approximately two-thirds of patients who
do respond to antidepressants are likely to report
partial improvement after 4 weeks of therapy.
51
The initial antidepressant should be
switched with another second-generation anti-
depressant (SSRI, SNRI, mirtazapine, or bupro-
pion) if improvement is not seen with 4 weeks of
a maximum tolerated dose or a partial response
is not obtained with 8 weeks of a maximum toler-
ated dose.
36
If a partial response is observed
after 8–12 weeks, then augmentation with
psychotherapy or with an additional agent is
recommended.
36
Lithium augmentation is the most studied
strategy in the older population, demonstrating
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383
an overall response rate of 42% when added to
antidepressant therapy.
52
However, this medica-
tion must be used cautiously because of the risk
of toxicity, caused mainly by age-related decline
in glomerular filtration. Other augmentation
strategies that have been studied in the elderly
include adding a different class of antidepres-
sant (response rate = 31% to 45%) or adding a
second-generation antipsychotic (response rate
= 33% to 50%).
52
Studies have suggested that older adults
are more likely to relapse or have a recurrence
of depression sooner after adequate treatment
compared to younger adults.
53
Therefore, main-
tenance therapy should continue for at least 1–2
years after remission is achieved.
36
Electroconvulsive erapy
A number of studies have shown electrocon-
vulsive therapy (ECT) to be effective in late-life
depression, with efficacy rates ranging from
60% to 80%.
54-56
This treatment is indicated for
treatment-resistant depression or for patients at
high risk of serious harm because of psychotic
depression or suicidal ideation. ECT is usually
administered three times weekly for 2–6 weeks
(total of 6–12 treatments) in an inpatient psychi-
atric setting, which limits its utilization. Common
adverse effects include headache, temporary
amnesia, and cognitive impairment. Perma-
nent memory loss of the events surrounding the
ECT treatments is a rare event but can occur.
24
After ECT treatment is completed, maintenance
therapy with an antidepressant medication is
recommended to decrease the risk of relapse.
36
Common Problems Encountered
When Treating Elderly Patients
Selective Serotonin Reuptake Inhibitors
Overall, SSRIs do not antagonize muscarinic,
histaminic, or adrenergic receptors. Therefore,
the common adverse effects observed with TCAs
and monoamine oxidase inhibitors are not usually
a concern with most SSRIs.
10
The exception is
paroxetine, which has moderate antimuscarinic
activity—one reason it is not recommended as
a first-line SSRI for the elderly.
10
Compared to
TCAs, cardiotoxicity is rare with SSRIs. However,
a recent Food and Drug Administration (FDA)
warning regarding citalopram was published in
2011 recommending lower dosing of citalopram
(20 mg or less) in the elderly because of increased
risk of prolonged QTc interval.
57
Common adverse
effects associated with SSRIs are due to increased
activity at serotonin receptors. Gastrointestinal (GI)
symptoms such as nausea, vomiting, and diar-
rhea are frequently noted. SSRIs are also associ-
ated with sexual dysfunction, appetite suppres-
sion, and sleep changes (both hypersomnia and
insomnia).
10,49
Fluoxetine is associated with more
anxiety and agitation compared to other SSRIs.
Because of these adverse effects and its long half-
life, fluoxetine is not considered a first-line SSRI for
older adults.
36
There are particular SSRI adverse effects
more prevalent in the elderly than in younger
adults. These include hyponatremia, extrapyra-
midal adverse effects, and increased bleeding.
SSRI-induced hyponatremia occurs in 10% to
15% of older adults and is more common in
women. Paroxetine appears to have the highest
incidence within this class. The hyponatremia
is likely the result of increased secretion of anti-
diuretic hormone.
10,58
Extrapyramidal side effects
such as parkinsonism, dystonia, and akathisia
are observed in 10% of older adults taking
SSRI therapy. These effects are possibly due to
decreased nigrostriatal dopaminergic transmis-
sion indirectly caused by increased serotonin
activity.
10,49
Bleeding risk appears to be higher
in elderly patients who take SSRIs compared to
younger adults.
59
GI bleed risk is increased when
these agents are taken concurrently with nonste-
roidal anti-inflammatory drugs.
60
Bleeding risk is
possibly due to SSRIs preventing platelet reup-
take of serotonin, resulting in decreased platelet
action.
49
Bleeding risk should be assessed and
monitored closely, especially for patients taking
antiplatelets and anticoagulants concurrently with
SSRI therapy.
All SSRIs are metabolized by cytochrome
P450 enzymes. Paroxetine significantly inhibits
2D6 isoenzymes, whereas fluoxetine inhibits
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| Fundamentals of Geriatric Pharmacotherapy
2D6, 3A4, and 1A2, making these two agents
more likely to interact with other medications.
Sertraline weakly inhibits 2D6 at higher doses,
and citalopram and escitalopram have very little
inhibition activity, making these three agents the
preferred ones for elderly patients taking multiple
medications.
49
Serotonin and Norepinephrine Reuptake
Inhibitors
Venlafaxine, desvenlafaxine, and duloxetine
result in increased levels of serotonin and norepi-
nephrine in the synaptic cleft by inhibiting the
reuptake of these neurotransmitters back into the
presynaptic neuron. Patients who fail to respond
to SSRIs may find efficacy with SNRIs because
of the dual neurotransmitter effect. These agents
may also be beneficial for patients with concur-
rent neuropathic pain or fibromyalgia.
24
Studies
have shown venlafaxine and duloxetine to be
efficacious and well-tolerated in the elderly,
although one trial did suggest that venlafaxine
may be less well tolerated in the frail elderly
compared to SSRIs.
45-48,61
Serotonergic adverse effects such as GI
upset, sexual dysfunction, and sleep changes
are commonly observed with SNRIs. Cases of
hyponatremia have also been noted with venla-
faxine use. SNRIs should typically be given in
the morning because of the risk of insomnia if
given at bedtime. These agents are also associ-
ated with elevated blood pressure at high doses
(risk is greater for venlafaxine versus duloxetine);
therefore, blood pressure should be monitored
regularly with therapy.
10
Both venlafaxine and duloxetine are metab-
olized by the cytochrome P450 isoenzymes.
Venlafaxine has very weak inhibition, and dulox-
etine has moderate inhibition at the 2D6 pathway.
However, these effects have not been shown to
be clinically significant in most cases.
49
Desven-
lafaxine is an active metabolite of venlafaxine. It
has minimal P450 metabolism, and 45% of the
drug is excreted unchanged in the urine. There-
fore, lower dosing is recommended for patients
with reduced renal function.
62
Overall, SNRIs can
be used in older patients taking multiple medica-
tions without cause of concern, although dosage
recommendations should follow the standard
recommendation in older adults to “start low and
go slow, but go.”
Bupropion and Mirtazapine
Bupropion inhibits the reuptake of dopamine
and norepinephrine in the central nervous
system (CNS), causing an increase in these
neurotransmitters in the neuronal synaptic cleft.
Because of bupropion’s mechanism of action, it
is the most activating agent compared to other
antidepressants. Doses should not be taken at
night because of the risk of insomnia. There are
limited data on use of bupropion in the elderly,
63
but according to treatment guidelines it can be
considered as a first-line therapy.
36
Bupropion
may be useful for depression associated with
apathy, lack of motivation, and hypersomnia,
and data suggest it may have a role in augmen-
tation therapy when used in treatment-resistant
depression.
64
Common adverse effects of bupropion
include tremors, nervousness, and elevated
blood pressure and pulse. Bupropion is contra-
indicated in patients with a history of seizures
and should not be used in patients with anxiety
disorders. Compared to other antidepres-
sants, bupropion is most likely to cause appe-
tite suppression and weight loss and, therefore,
should be used cautiously in elderly patients
who have decreased oral intake. When using the
medication, blood pressure and pulse should be
monitored regularly.
6,24,29
Mirtazapine acts as a central alpha antago-
nist, resulting in increased release of serotonin
and norepinephrine in the CNS. This agent is
also a potent antagonist of histamine receptors
and, therefore, causes sedation and increased
appetite. Compared to the quantity of SSRI and
SNRI data, there is significantly less published
information regarding the efficacy of mirtazapine
in late-life depression. However, small studies do
suggest mirtazapine is as effective as other first-
line therapies and may be useful for depressed
elderly who also have decreased oral intake or
insomnia.
65,66
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385
Tricyclic Antidepressants
In general, TCAs work similarly to SNRIs by inhib-
iting the reuptake of both serotonin and norepi-
nephrine. However, each tricyclic agent has
varying degrees of potency on the reuptake trans-
porters, making some agents more serotonergic
and others more noradrenergic in action.
10
TCAs
are effective but less well tolerated in older adults
compared to SSRIs and SNRIs.
67
These agents
also inhibit cardiac sodium-potassium adenosine
triphosphatase (Na/K ATPase) pump and act as
antagonists at alpha, muscarinic, and histaminic
receptors, which can lead to significant adverse
effects. TCAs can worsen symptoms of chronic
conditions such as benign prostate hyper-
plasia, urinary retention, constipation, cognitive
impairment, glaucoma, orthostatic hypotension,
cardiac disease, and arrhythmias.
10,24
Secondary amines such as nortriptyline and
desipramine are associated with less anticholin-
ergic, antihistaminic, and orthostatic hypoten-
sion compared to the tertiary amines. However,
cardiac toxicity is equal among both groups of
drugs.
10,49
Compared to the other classes of anti-
depressants, TCAs are more likely to be fatal on
overdose. Even though TCAs have been proven
to be efficacious for late-life depression, they
should not be used as first-line therapy because
of the high risk of adverse effects.
36
If tricyclic
therapy is necessary, then nortriptyline is usually
recommended, as it has data to support its effi-
cacy as monotherapy
39,47
and as an augmenta-
tion agent
64,68
for patients who fail SSRI therapy.
Drug levels should be obtained and monitored.
A concentration of 80–120 ng/mL is the goal
range for efficacy and safety.
68
KEY POINT:
e benets of using SSRI
therapy as a rst-line agent for late-life
depression outweigh the risks. However,
geriatric patients are at higher risk of
developing hyponatremia, extrapyramidal
adverse eects, and GI bleeding with SSRI
therapy compared to younger adults.
A
Etiology, Epidemiology, and
Clinical Presentation Specic to
Geriatrics
Compared to late-life depression, fewer studies
exist and less is known about the presentation,
treatment, and prognosis of late-life anxiety
disorders.
69
The most recent epidemiologic data
found the prevalence rates of late-life anxiety
disorders to be around 7% within a recent
12-month period and 15% for lifetime occur-
rence.
70,71
Research shows that anxiety disorders
are common in late life; however, they appear to
be less prevalent in older adults compared to
younger adults.
70,72
These results may certainly
be true, but it is suspected that many cases of
late-life anxiety are not being detected properly
or symptoms are being misdiagnosed.
73,74
Comorbid anxiety and depression are
observed three times more often than pure
anxiety.
69,75
The prevalence of older adults with
anxiety who also suffer from major depressive
disorder ranges from 13% to 30%.
76-78
Elderly
patients with both depression and GAD are more
likely to have severe, chronic depressive symp-
toms and suicidal ideation compared to those
suffering only from depression.
79
In addition,
older adults suffering from any anxiety disorder
with depression have lower social functioning
and require increased health services compared
to elderly patients with pure anxiety.
79,80
Anxiety disorders is a broad term that
includes multiple individual disorders such
as GAD, panic disorder, specific phobias,
social anxiety disorder, obsessive-compul-
sive disorder (OCD), acute stress disorder,
and post-traumatic stress disorder (PTSD).
In the recently published DSM-5 text, OCD
was moved from Anxiety Disorders to a new
chapter entitled “Obsessive-Compulsive and
Related Disorders,” and PTSD was moved
to “Trauma and Stressor-Related Disor-
ders.”
21
The most common anxiety diagnoses
observed in older adults are GAD and specific
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386
| Fundamentals of Geriatric Pharmacotherapy
phobias. Table 13-2 provides an overview of
the diagnostic criteria for each anxiety disorder
and its prevalence in the geriatric population.
Limitations in Identifying Anxiety
Disorders, Risk Factors, and
Presentation Specic to Geriatric
Patients
Data from the National Comorbidity Survey
Replication study showed that less than 1% of
the population developed a newly diagnosed
anxiety disorder after 65 years of age, demon-
strating that most late-life anxieties likely devel-
oped in early adulthood and persisted through
the older years.
70
However, GAD appears to
be the exception. Episodes of late-life GAD are
found to be an even combination of chronic
patients who report having anxiety symptoms
since early adulthood and patients whose symp-
toms started in late life.
69,75
Noted risk factors are female sex, having
medical comorbidities, being single or divorced,
lower education, low subjective health, stressful
life events, limitations with daily activities, and
neuroticism.
73
Older adults with late-life anxiety
often present to their primary care provider
complaining of unexplained physical symptoms
such as fatigue, aches, pains, GI symptoms, or
trouble sleeping, which may result in a delay of
the correct diagnosis.
75
As stated earlier, it is suspected that late-life
anxiety may be underdiagnosed. Detection and
diagnosis of late-life anxiety can be complicated
by patients’ medical comorbidities, decreased
cognition, and changes in life circumstances.
Specific factors that may contribute to poor
screening and diagnosis include (1) clinicians
and patients assuming anxiety and avoidance
behaviors are normal with aging, (2) patients
minimizing their emotional symptoms, (3)
patients attributing their anxiety symptoms to
physical illnesses, (4) patients’ difficulty remem-
bering their symptoms, and (5) older adults
experiencing more fear or worry about different
situations than younger adults.
74,81,82
KEY POINT:
ere is a high prevalence
of comorbid depression with late-life
anxiety. Patients who meet diagnostic
criteria for anxiety should also be
screened for major depressive disorder.
Summary of Standard Treatment in
the Adult Population
Goals of treatment for all patients with anxiety
disorders include decreasing anxiety severity,
improving level of function, and obtaining remis-
sion. For acute treatment, benzodiazepines are
the only pharmacologic treatment available with
a quick onset of action. They may also need to
be used for chronic treatment for patients who
obtain only a partial response with antidepres-
sants. Guidelines recommend SSRIs and SNRIs
as first-line agents for the chronic treatment of
most anxiety disorders. If first-line agents are
ineffective, then TCAs can be tried.
83
Buspirone
can also be considered as a second- or third-
line agent for chronic treatment of GAD.
84
After
an adequate response is achieved, treatment
should generally continue for at least 12 months.
Long-term therapy is recommended for patients
with multiple episodes of anxiety.
83
Cognitive-
behavioral therapy (CBT) has been shown to be
equally efficacious for treatment of anxiety disor-
ders compared to pharmacotherapy for younger
adults and, if available, patients may choose this
option over drug therapy.
83,84
Review of Evidence Supporting
Treatment Recommendations for
Geriatric Patients
Psychotherapy
Although drug therapy is often recommended for
late-life anxiety, psychotherapy may also be effi-
cacious and preferred for older adults who are
sensitive to medication adverse effects or trying
to avoid polypharmacy. CBT is the most studied
psychotherapy in older adults with anxiety and
may include breathing retraining, muscle relax-
ation, cognitive restructuring to focus on the
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