CASE 31

A 75-year-old Caucasian female is requesting psychiatric consultation because of the

painful awareness that she is declining cognitively and emotionally. Six months ago, a
neurologist recommended that she discontinue her part-time job because of her
diminishing memory capacity. On hearing the doctor’s advice, she became intensely
anxious about the future. Notably, she dreaded that her memories of herself and her
loved ones would soon fade and disappear, and the sense of continuity, connection and
self-identity that have grounded her would be lost forever. Horrified at the idea of total
incapacitation, her anxiety developed into a sense of impending doom, as she became
increasingly unable to perform certain tasks. Easily agitated and no longer able to
effectively calm herself, she reacted to irritations with all-consuming worries, a sense of
helplessness, and despair. Worn out from having to sustain herself each day, she
experienced aches and pains, fatigue, insomnia and poor appetite. Her world began to
seem like an “unjust place”, where too many things seemed outside of her control. In an
effort to stay in charge, she spoke of wanting to actively bring about her own demise,
rather than helplessly succumbing to what felt like slow mental death. Overly sensitive
about others’ perception of her, she believed that they blamed her for her cognitive
shortcomings. To keep from feeling vulnerable to criticism, she restricted her activities
and commitments, isolating herself by rigidly holding to the familiar features of her home
surroundings. The gradual loss of her mental faculties reactivated experiences of
previous losses and difficult sacrifices she had to make in the past. Her psychiatric
history was notable for several previous episodes of depression and suicidal ideation,
initially triggered by the loss of her husband to cancer 20 years ago. Her previously
diagnosed mood disorder, manifested by anhedonia, psychomotor retardation, weight
loss, and sleep disturbance had been well controlled with medications until the present
recurrence.

What are the most likely diagnoses?

What is your next diagnostic step?

What is the next step in the management?

ANSWERS TO CASE 31:

Depression
Summary: This 75-year-old female presents with a history of recurring depression and
anxiety, with the first episode developing after her husband’s death 20 years ago. The
previously diagnosed mood disorder was well controlled with medications. The current
recurrence of mood problems is triggered by her cognitive decline and the loss of a part-
time job. Her symptom profile includes depressed mood most of the day, characterized
by irritability and agitation, thoughts of death, diminished interest and pleasure in social
activities, insomnia, appetite disturbance, loss of energy when completing day-to-day
tasks, feelings of worthlessness and helplessness. In addition, she exhibits excessive
anxieties and worries about a number of different facets of her life and difficulty
modulating these emotions. The symptoms do not seem to meet criteria for a mixed
bipolar episode, are not due to substance use, or better accounted for by a grief
reaction. She clearly presents with clinically significant distress and impairments in
social and occupational functioning.

Most likely diagnoses: Major depressive disorder, recurrent, moderate;

generalized anxiety disorder (GAD); cognitive disorder not otherwise specified
(NOS); rule out mild cognitive impairment versus probably dementia of the
Alzheimer’s type.
Next diagnostic step: Standardized depression and anxiety screening measures
and depression scales can include the Geriatric Depression Scale, the Beck
Depression Scale, or the Cornell Scale for Depression in Dementia. Anxiety
scales can include the Beck Anxiety Inventory; the Hamilton Anxiety Rating Scale;
or the State and Trait Anxiety Inventory. Cognitive screens may include the Mini-
Mental State Examination, 2nd Edition: Extended Version, or the Montreal
Cognitive Assessment.
Next step in the management: Begin psychotropic medications with demonstrated
efficacy in the treatment of comorbid conditions of depression and anxiety
disorders. The main FDA-approved indication for selective serotonin reuptake
inhibitors (SSRIs) is major depressive disorder (MDD); however, they are
frequently prescribed for anxiety disorders, such as social anxiety disorder, GAD,
panic disorder, obsessive compulsive disorder, or posttraumatic stress disorder.

ANALYSIS
Objectives
1. To describe new, emerging strategies in the assessment and treatment of MDD
and GAD.
2. To understand the comorbidity and pathophysiology of depression and anxiety.
3. To be familiar with early identification and intervention (eg, suicide potential in
depression).
4. To describe intended/unintended effects of therapeutic interventions.
Considerations
This 75-year-old patient presented with comorbid mood and anxiety disorder, triggered
by her recent physical and cognitive decline. The two most important psychiatric issues
for this patient are (1) the challenge of diagnosing and treating the comorbid conditions
of depression, anxiety, and cognitive disorder and (2) deciding whether the patient has
indications or contraindications for certain psychotropic medications and/or
psychotherapy. While anxiety and depression are commonly thought to be distinct
disorders, in older adults, there is much overlap in terms of symptoms, making
differential diagnosis difficult. For example, both anxiety and depression involve
impaired concentration, memory, irritability, fatigue, insomnia, and a sense of
hopelessness. Difficulties with concentration, problem-solving ability, and memory can
also manifest in both anxiety and affective disorders, making it difficult to differentiate
them from a dementia process. In general, depressive disorders can be distinguished
from anxiety disorders based on a thorough review of the patient’s medical history.
While anxiety and depression both involve negative affect, anxiety is usually associated
with a higher level of positive affect and autonomic arousal. Apprehension, attention,
trembling, excessive worry, and nightmares are “pure” anxiety symptoms, while
depressed mood, anhedonia, loss of interest in usual activities, suicidal ideation, and
decreased libido are “pure” depressive symptoms.
Regarding this patient’s diagnosis, consideration may be given to the diagnosis of
Mood Disorder Due to a General Medical Condition, as some of her current symptoms
seem to be associated with the presence of a medical condition. However, given that
her mood disorder is not a direct physiological consequence of a medical condition, but
a reaction to it, and the most recent recurrence, at least in part, is an extension of other
preexisting depressive episodes, her clinical profile is better accounted for by a
diagnosis of Major Depressive Disorder. Considering criteria for MDD, the following five
symptoms have distressed her for more than 2 weeks: 1) depressed mood,
characterized by episodes of anger and combativeness nearly every day, most of the
day; 2) diminished interest and pleasure in social activities, 3) psychomotor agitation, 4)
loss of energy when completing day-to-day tasks, 5) feelings of worthlessness and
helplessness, 6) diminished ability to think due to cognitive decline, and 7) recurrent
thoughts of death.
Considering this patient’s excessive anxiety about a number of different facets of her
life as well as her inability to control worries, along with the symptoms of irritability and
fatigue, she also meets criteria for Generalized Anxiety Disorder. In addition, based on
the clinical information and the neurological exam, the patient should be considered for
diagnosis of Cognitive Disorder NOS. A referral for a comprehensive
neuropsychological evaluation may help clarify the extent, nature and etiology of the
cognitive disorder.
As far as psychopharmacology, considerations for choosing optimal antidepressants
include 1) efficacy, 2) side effects, 3) drug vs. drug interactions, and 4) price of
medication. SSRIs have the advantage that they are effective, safe, tolerable, easy to
use, less cardiotoxic than tricyclic antidepressants (TCAs), and less likely to produce
cognitive impairment. The starting dose is usually a therapeutic dose, given once daily
and effective for both anxiety disorders and depression. A good first choice of SSRI for
this comorbid patient would be citalopram (Celexa), as it is inexpensive and has minimal
drug interaction potential. All SSRIs may cause insomnia, agitation, sedation,
gastrointestinal distress (nausea, appetite loss, constipation or diarrhea), however
citalopram is relatively well tolerated among the elderly. Escitalopram (Lexapro), the S-
stereoisomer (enantiomer) of citalopram, would be another good choice, however it is
expensive. Sertraline (Zoloft) would also be effective with vascular headaches, although
more sedating than citalopram. Many SSRIs, such as fluoxetine (Prozac) and
paroxetine (Paxil), inhibit various cytochrome P450 isozymes as well as the activity of
P-glycoprotein that make drug metabolism possible, therefore those SSRIs would not
be the first choice for the elderly. Co-administration with cholinesterase inhibitors, such
as donepezil (Aricept), may increase the plasma concentrations of donepezil, primarily
metabolized by these isoenzymes.
Norepinephrine-dopamine reuptake inhibitors (NDRIs), such as bupropion
(Wellbutrin), may be more effective than SSRIs at improving symptoms of hypersomnia
and fatigue in depressed patients, are less cardiotoxic than the TCAs and often effective
in individuals who have not responded to other antidepressants. Serotonin antagonist
and reuptake inhibitors (SARIs), such as trazodone (Desyrel), may be administered in
low doses for patients with insomnia, as it has sleep inducing/enhancing effects. For
older patients with a history of chronic pain, osteoarthritis, or diabetic neuropathy,
selective serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine
(Cymbalta), can be used to treat muscle or bone pain and tingling due to nerve damage.
Because SNRIs can increase blood pressure, frequent monitoring is required.
Available SNRIs, such as venlafaxine (Effexor) that show an onset of action within the
first week of treatment can help with Resolution of anxiety early in the course of
treatment. This may be important if there is a question as to the patient’s compliance
with their antidepressant regimen and a possible premature discontinuation from
treatment. Venlafaxine in patients with comorbid MDD and GAD was found to have
greater efficacy as compared to fluoxetine. Any high-potency short-to-intermediate
acting benzodiazepines can cause strong amnesic effects, confusion, drowsiness,
slurred speech, ataxia and falls in the elderly, therefore contraindicated. In some cases,
there can be paradoxical effects with benzodiazepines, such as increased hostility,
disinhibition, aggression, angry outbursts, disorientation, and psychomotor agitation,
although paradoxical excitement may also occur in older individuals.
Because comorbid anxiety is often associated with the development of chronicity in
depression and treatment resistance, psychotherapy serves an important adjunct in
managing patients with these comorbidities. A careful psychiatric evaluation may help
determine suitability to the different psychotherapeutic modalities (psychodynamic,
cognitive behavioral, or supportive). Life review is an effective therapeutic practice for
older adults with depressive symptomology, using autobiographical retrieval.

APPROACH TO:
The Patient with Depression and Anxiety

DEFINITIONS
MAJOR DEPRESSIVE DISORDER (DIAGNOSTIC AND STATISTICAL MANUAL OF
MENTAL DISORDERS, 4TH EDITION, TEXT REVISION [DSM-IV-TR] criteria): MDE
requires the presence of depressed mood or anhedonia of at least 2 weeks’ duration
with at least 4 of the following:
(1) decreased interest or pleasure most of the time; (2) significant change in weight
when not dieting; (3) insomnia or hypersomnia (in the elderly: increased pain and
overlap with effects of medications and comorbid conditions); (4) psychomotor agitation
or retardation; (5) fatigue or loss of energy, feelings of worthlessness, inappropriate
guilt; (6) decreased concentration or thinking, indecisiveness (in the elderly:
multidomain cognitive decline); and (7) recurrent thoughts of death or suicide (in the
elderly: thoughts of death). There is no evidence of a medical/substance etiology/mixed
episode, no uncomplicated bereavement, but significant distress or impairment

GENERALIZED ANXIETY DISORDER (DSM-IV-TR CRITERIA): GAD involves

excessive anxiety and worry occurring more days than not for at least 6 months, about a
number of events or activities that the person finds difficult to control, and are
disproportionate to the feared events or the potential impact. The anxiety and worry
must entail at least 3 of the following 6 symptoms: (1) restlessness or feeling keyed up
or on the edge, (2) being easily fatigued, (3) difficulty concentrating or mind going blank,
(4) irritability, (5) muscle tension, or (6) sleep disturbance (difficulty falling or staying
asleep, or restless unsatisfying sleep). The anxiety, worry, or physical symptoms cause
clinically significant distress or impairment in social, occupational, or other important
areas of functioning. The disturbance is not due to the direct physiological effects of a
substance or a general medical condition and does not occur exclusively during a mood
disorder, a psychotic disorder

MOOD DISORDER DUE TO A GENERAL MEDICAL CONDITION (DSM-IV-TR

CRITERIA): A prominent and persistent disturbance in mood predominates the clinical
picture and is characterized by either (or both) of the following: (1) depressed mood or
markedly diminished interest or pleasure in all, or almost all, activities; and (2) elevated,
expansive, or irritable mood. There is evidence from the history, physical examination,
or laboratory findings that the disturbance is the direct physiological consequence of a
general medical condition. The disturbance is not better accounted for by another
mental disorder and it does not occur exclusively during the course of a delirium. The
symptoms cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning

CLINICAL APPROACH
Etiologies
Depression MDD is thought to be linked to neurotransmitter abnormalities. The
catecholamine hypothesis proposes that some forms of depression are due to a
deficiency in norepinephrine, while the indolamine hypothesis states that depression is
due to low levels of serotonin. Depression has also been linked to elevated levels of
cortisol, secreted by the adrenal cortex. Some investigators have proposed an
association between depression and lack of new cell growth in certain parts of the brain,
especially in the left subgenual prefrontal cortex (involved in the control of positive
emotions), and in the hippocampus.
Behavioral and cognitive behavioral theories offer alternatives to biological
explanations for depression. In particular, the learned helplessness model describes
depression as a result of prior exposure to uncontrollable negative events coupled with
a tendency to attribute those events to internal, stable, and global factors, rather than
external, transient, and specific factors.
In terms of pathophysiology, neither genetics nor neurotransmitter dysfunction have
been proven to play an important role in the etiology of “late-life depression.” Some
argue, however, that endocrine dysregulation over time, due to stress or other causes,
is associated with anatomical changes, such as reduction in the size of hippocampus.
These endocrine and neuroanatomical changes can result in depressive symptoms in
the elderly (Sapolsky, 1996, 2001; Sheline et al, 1996; Steffens et al, 2002). Others
hypothesize that cerebrovascular disease contributes to depression in late life.
“Vascular depression” is suggested to be one of the consequences of common risk
factors, such as hypertension, diabetes, hyperlipidemia, and smoking. Symptoms can
include executive dysfunction, reduced verbal fluency, and psychomotor slowing. These
symptoms overlap with signs of dementia and may be difficult to discern. In general,
impaired function due to disability or dementia is thought to be the chief cause of
depression in the elderly. Other factors such as a preexisting psychological condition,
social isolation, and low socioeconomic status can also contribute to it.

Anxiety Anxiety disorders are less prevalent in the elderly than in younger adults;
however, anxiety conditions may be twice as common as depression in older adults.
GAD is the most common anxiety disorder among the elderly. It is most likely to cause
cognitive impairment, sleep disturbances, and problems with carrying out the activities
in older versus younger adults. New-onset anxiety is often secondary to medical illness,
depression, side effects, or withdrawal from drugs.
Diagnostic Criteria
Episodes of depression can occur with remissions throughout life. However, as
individuals age, these episodes may become so frequent that there is no respite.
Recurrent depression can morph into a constant condition. An Australian study followed
elderly patients who had experienced severe depression early in life and found that only
12% were fully remitted and free of relapse over the observation period. Overall
prevalence rates range from 7% to 36% in medical outpatients and increase to 40% in
hospitalized elderly patients.
The geriatric presentation of depression may look different than what is
typically seen in general adult population. In the elderly, cognitive symptoms may
be more prominent, consisting of decreased selective attention, decreased working
memory, reduced new learning, decreased processing speed and executive
dysfunction. Depressed mood can be characterized by weariness, hopelessness, and
anger. Anhedonia may present as anxiety. Suicidal thoughts can be more about
thoughts of death. Somatic symptoms can overlap with effects of medications and
comorbid disease.
The latest literature points to a distinct depressive syndrome associated with
Alzheimer disease, typically characterized by fewer and less prominent symptoms than
the DSM-IV-TR criteria symptoms of major depression. Alternatively, patients with a
history of recurrent depression (early onset) often have symptoms similar to their
previous episodes.
With respect to comorbidity, patients with comorbid anxiety often present with somatic
symptoms, such as pain, shortness of breath, changes in appetite, or insomnia. The
discerning physician must look past the somatic aspects and recognize the psychiatric
issues at hand. Familiarity with common presentations of depression, anxiety, and
comorbidity will make it easier to identify indicating features. Patients frequently present
with primary somatic complaints, while symptoms of anxiety and depression are
intermingled with real-life problems about which the patient has little or no insight.
Comorbid depression usually indicates a worse prognosis.
History
In taking a psychiatric history, careful attention should be paid to the patient’s mental
status, appearance, and self-care. In completing a mental status examination, it is
important to see if there is a baseline cognitive assessment that has been done. Mood
disorders can be mistaken for weariness. The mental content of the patient’s speech
may refer to somatic preoccupations, pain, and complains about cognitive functioning.
Objective scales provide a benchmark for evaluation and treatment and may facilitate
patients’ reporting to accurately estimate severities of a potential mood or anxiety
disorder, or dementia (see Table 31–1).

Table 31–1 • GERIATRIC DEPRESSION SCALE—15 ITEMS

1. Are you basically satisfied with your life?

2. Have you dropped many of your activities and interests?

3. Do you feel that your life is empty?

4. Do you often get bored?

5. Are you in good spirits most of the time?

6. Are you afraid that something bad is going to happen to you?

7. Do you feel happy most of the time?

8. Do you often feel helpless?

9. Do you prefer to stay at home, rather than going out and doing new things?

10. Do you feel you have more problems with memory than most?

11. Do you think it is wonderful to be alive now?

 12. Do you feel pretty worthless the way you are now?

13. Do you feel full of energy?

14. Do you feel that your situation is hopeless?

15. Do you think that most people are better off than you are?

(Reproduced, with permission, from Yesavage JA, Brink TL, Rose TL, et al.
Development and validation of a geriatric depression screening scale: a preliminary
report. J Psychiatr Res. 1982-83;17(1): 37-49.)
To score the GDS 15, give 1 point for each “Yes” on 2, 3, 4, 6, 8, 9, 10, 12, 14, 15 and
each “No” on 1, 5, 7, 11, and 13. A score of 6 or higher suggests need for definitive
diagnostic evaluation.

Detection of depression may also require collateral informants. The Cornell Scale for
Depression in Dementia (CSDD), Table 31–2 was specifically developed to assess
signs and symptoms of major depression in patients with dementia. Because some of
these patients may give unreliable reports, the CSDD uses a comprehensive
interviewing approach that derives information from the patient and an informant.
Information is elicited through 2 semistructured interviews; an interview with an
informant and an interview with the patient.

Table 31–2 • CORNELL SCALE FOR DEPRESSION IN DEMENTIA

 In differentiating between dementia syndrome of depression (DSD) versus Alzheimer
disease (AD), considerations should include symptom duration (short in DSD vs long in
AD), prior psychiatric history (usual in DSD vs unusual in AD), patient complaint
(frequent in DSD, variable in AD), behavior congruent with cognitive deficits (unusual
with DSD, usual in AD). Mood disorder is autonomously part of DSD, while it is reactive
in AD. Recognition memory is intact in DS, but impaired in AD. Effort on tasks is usually
poor in DSD, but reasonably good in AD. Cuing is helpful in DSD on recognition
memory tasks, while less or not at all helpful in AD. Other differential diagnoses to be
considered include bereavement and adjustment disorder, bipolar disorder, substance
abuse disorders, anxiety disorders, personality disorders, and schizophrenia.
Medical history and physical examination is an essential component of the psychiatric
workup. Medications that may cause symptoms of depression include anabolic steroids,
antiarrhythmic medications, anticonvulsant medications, barbiturates, benzodiazepines,
carbidopa or levodopa, certain β-adrenergic antagonists, clonidine, cytokines
(specifically IL-2), digitalis preparations, glucocorticoids, H2 blockers, metoclopramide,
and opioids. Medications that may cause anxiety include corticosteroids,
antidepressants, neuroleptics, stimulants, sympathomimetics (pseudoephedrine, β-
agonists), and thyroid hormone overreplacement. Full attention needs to be paid to
toxicities; cardiovascular (arrhythmias, angina), respiratory (COPD, asthma), and
neurological disorders (movement disorders); endocrine (hyperthyroidism,
hypoglycemis) and metabolic disorders; nutritional deficiencies, sleep disorders,
infectious disorders, and neoplasms, as these medical conditions can cause depression
and/or anxiety. On physical examination, focusing on signs and symptoms of anxiety
(tachycardia, hyperpnea, seating, and tremor) is important.
Labs
The following labs should be considered. For anxiety, consider CBC, differential, blood
glucose, thyroid function tests, vitamin B12, ECG, and drug and alcohol screening. For
depression, consider TSH, calcium, LFTs, renal function test, electrolytes, UA, and
CBC. Other diagnostic interventions to be considered (not considered routine):
neuropsychological testing and neuroimaging studies.
Treatment
Depression in the elderly is an underrecognized illness with severe consequences in
function and mortality. Failure to treat comorbid depression and anxiety can result in
functional decline and increased disability. Psychotherapy, medication, and
electroconvulsive therapy have each been shown to be effective treatment and
individualized treatment should be tailored to the specific patient’s needs.

Nonpharmacologic In the elderly, factors inhibiting engagement in therapy may include

the patient’s age-related perceptions that time is limited and that their self is fixed and
unchangeable. Their physical limitations, including hearing and vision loss, ambulatory
problems, physical discomfort, and transportation difficulties may also contribute to
reduce adherence to office visits. There may be some cognitive limitations as to not
being able to retain the content of the sessions from week to week. However, when
modifications are applied to late life therapies outcomes have been generally positive.

Pharmacologic In confirming the diagnosis to determine the need for

pharmacotherapy, the practitioner must ask if the patient meets criteria for depression,
whether the patient is currently taking a drug that may be causing or contributing to
depressive symptoms, whether there is an underlying medical condition contributing to
the patient’s depressive symptoms, and if these conditions have been addressed. In
evaluating the effects of antidepressant therapy, it is important for the practitioner to
have a way to measure the patient’s response to antidepressant therapy, to assess at 4
to 6 weeks for noticeable improvement in target symptoms, for remission at 8 to 12
weeks, and for noticeable improvement at the maximal tolerated dose.
Some of the marketed antidepressants used for late-life depression include tricyclic
antidepressant (nortriptyline [Pamelor]), MAO inhibitors (phenelzine [Nardil];
tranylcypromine [Parnate]; selegiline [Emsam]), SSRIs, SNRIs, and others (bupropion
[Wellbutrin]; mirtazapine [Remeron]). Older adults are more vulnerable than younger
adults to anticholinergic side effects of antidepressants. SSRIs should be considered for
mild to moderate depression, patients with heart defects, ischemic heart disease,
uncontrolled glaucoma, and prostatic hypertrophy. Nortriptyline or desipramine may be
considered as a second line of treatment for severe depression and also for patients
with urge incontinence. Certain older types of antidepressants, such as amitriptyline and
imipramine, can be sedating and cause a sudden drop in blood pressure when a person
stands up, which can lead to falls and fractures. NE reuptake blockages can cause
tremors, tachycardia, erectile/ejaculatory dysfunction, and elevated blood pressure.
Serotonin reuptake blockades may result in GI symptoms, sexual dysfunction, EPS,
bruising/bleeding, and bone mass density loss. Electroconvulsive therapy is usually less
efficacious than antidepressants in treating late-life depression with psychotic features.
For anxiety disorders, SSRIs are the initial treatment for OCD and panic disorder.
Benzodiazepines and buspirone are primary treatments for GAD. Secondary treatments
for OCD and panic disorder include β-blockers and neuroleptics.

PROGNOSIS
While depressive symptoms tend to fluctuate, anxiety symptoms are more constant over
time. As far as prognosis is concerned, comorbid depression, and anxiety in the elderly
results in less favorable outcomes, more medications, greater suicidal ideation, greater
chronicity, and slower recovery. Antidepressants may take longer to start working in
older people than they do in younger people. Since elderly people are more
sensitive to medicines, doctors may prescribe lower doses at first. For mild to moderate
or severe depression, the duration of therapy should be at least 6 months following
remission for patient experiencing their first depressive episode. Patients with a history
of major depression need to be treated for a minimum of 12 months following remission.
In those comorbid patients whose anxiety is treated first, prognosis may be better for
treatment compliance with antidepressant regimen.

COMPLICATIONS
Depression in the elderly is more likely to lead to suicide, with elderly white men
at greatest risk. Suicide rates in ages 80 to 84 are more than twice that of the general
population. Individuals aged 65 and older account for 19% of all deaths by suicide. The
risk factors for depression often seen in the elderly are certain medicines or combination
of medicines, social isolation and living alone, recent bereavement, presence of chronic
or severe pain, damage to body image, fear of death, history of depression, family
history of MDD, past suicide attempt, and substance abuse. Physical illness is the most
frequent stressor in suicides over 80 years of age.
 Depression is common in patients recovering from a myocardial infarction (MI) and is
an independent risk factor for early mortality. Older post-MI patients with depression
have more comorbidities than older patients without depression. Mood symptoms on a
self-reported rating scale were associated with 12- to 24-month mortality after stroke.
Depressed patients aged 65 and older were less likely to adhere to their diet, to take
prescribed medications, exercise regularly, or increase social support.
Depression has been found to exacerbate Alzheimer disease by increasing the speed
of progression and resulting disability. In the case we reviewed, the patient’s mood and
anxiety disorder most probably hastened the progression of the cognitive decline, as
she found herself nearly incapacitated with certain tasks in just six months’ time.

CLINICAL CASE CORRELATION

See also Case 24 (Syncope), Case 25 (Cardiovascular Accident (CVA)), Case 26

(Complex Partial Seizure), Case 28 (Parkinson Disease), Case 29 (Sensory
Impairment/Presbycusis), and Case 30 (Cognitive Impairment).

COMPREHENSION QUESTIONS

31.1 A 71-year-old healthy retiree has been taking fluoxetine since his late 40s. His
first major depressive episode was characterized by marked loss of interest
most of the day, nearly every day, for a 4-week period, as well as psychomotor
retardation, feelings of worthlessness, and suicidal ideation. His depression
was well controlled on medication. Recently, he sustained a mild traumatic
brain injury while on a road trip. Prior to the accident, the patient used to play
on his country club’s senior tennis team and planned to propose to his lady
friend of two years. Since the accident, he has been increasingly agitated,
impulsive, and depressed. He does not return his girlfriend’s calls, often sleeps
through the day and wishes he had died in the accident. He denies intrusive
and distressing recollections of the car accident. What is the most likely
diagnosis?
A. Major depressive disorder, recurrent, moderate
B. Generalized anxiety disorder
C. Mood disorder due to a general medical condition
D. Posttraumatic stress disorder

31.2 A 67-year-old woman presents with depressed mood, loss of interest, and
weakness. She reports feeling “good for nothing” and admits to anhedonia and
passive suicidal ideation. Her medical history indicates that she is taking
medications for high blood pressure, recently had a hysterectomy, and suffered
a mild heart attack when she was 51-years-old. Which of the following
medications would be best to treat her symptoms, while taking into account
efficacy, cost, age, and side effects?
 A. Escitalopram
B. Paroxetine
C. Tricyclics
D. Citalopram

31.3 Which hypothesis suggests that depression is due to the deficiency of

norepinephrine?
A. Indolamine
B. Norepinephrine
C. Catecholamine
D. Serotonin

ANSWERS

31.1 C. Consideration could be given to Major depressive disorder, due to a history

of a previous depressive episode and long-term antidepressant treatment.
However, the patient’s depression has been well controlled with medication,
and the most recent depressive episode does not appear to be a direct
extension of a premorbid depressive episode. Rather, it appears that the
current mood disturbance is primarily a direct physiological consequence of TBI
and is best explained by the patient’s general medical condition. Posttraumatic
stress disorder is not the correct diagnosis, as the patient denies intrusive
recollections of the traumatic event and there is no indication that he is
avoiding stimuli associated with the car accident.

31.2 D. Citalopram is the best answer when considering both efficacy and cost
effectiveness. Paroxetine inhibits various cytochrome P450 isozymes as well
as the activity of P-glycoprotein that make drug metabolism possible. Therefore
Paroxetine is not the best choice for an elderly patient. Tricyclic
antidepressants are more cardiotoxic than SSRIs and should be avoided in this
patient with a history of myocardial infarct.

31.3 C. The catecholamine hypothesis proposes that some forms of depression are
due to a deficiency in norepinephrine, while the indolamine hypothesis states
that depression is due to low levels of serotonin.

CLINICAL PEARLS

While anxiety and depression are commonly thought to be distinct disorders, in

older adults, there is much overlap in terms of symptoms, making differential
diagnosis difficult. New diagnostic advances, however, allow for more refined
criteria to distinguish between discrete depressive or anxiety disorders, or mixed
conditions.
 Resolution of anxiety early in the course of treatment improves patients’ compliance
with their antidepressant regimen.

Older adults typically take more concurrently prescribed medications than younger
adults, necessitating that pracitioners pay meticulous attention to antidepressant-
associated drug–drug interactions.

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