PSYCHIATRIC ANNALS 44:3 | MARCH 2014 Healio.

com/Psychiatry | 131
CME
ABSTRACT
The diagnosis and treatment of late-
life depression is often complicated by its
clinical context.As a rule, late-life depres-
sion aficts medically ill, disabled persons
living under chronic stress and/or isola-
tion. Symptoms and signs of medical ill-
nesses and behavioral limitations from
disability are often difcult to distinguish
from depressive symptomatology.Under-
reporting of depressed mood and other
psychological symptoms is common by
older adults and contributes to under-
diagnosis of depression. Many antide-
pressant drugs and some psychothera-
pies have been found more efcacious
than their respective comparison condi-
tions. However, each of these treatments
helps less than half of depressed older
adults, necessitating a treatment strat-
egy in which failure or intolerance of each
treatment step informs the next. Clinical
subpopulations of late-life depression
psychotic depression, dysthymic disorder,
depression associated with an adverse
life event, treatment-resistant depression,
and residual symptoms of depression
require special attention.
Jimmy N. Avari, MD, is an Instructor in Psy-
chiatry, Weill Cornell Institute of Geriatric Psy-
chiatry, Department of Psychiatry, Weill Cor-
nell Medical College. Genevieve S. Yuen, MD,
PhD, is a Postdoctoral Research Fellow, Weill
Cornell Institute of Geriatric Psychiatry, De-
partment of Psychiatry, Weill Cornell Medical
College. Bassem AbdelMalak, MD, is a Visiting
Researcher, Weill Cornell Institute of Geriatric
Psychiatry, Department of Psychiatry, Weill
Cornell Medical College. Nahla Mahgoub,
MD, is Assistant Professor of Psychiatry, Weill
Cornell Institute of Geriatric Psychiatry, De-
partment of Psychiatry, Weill Cornell Medical
College. Balkrishna Kalayam, MD, is Associate
Professor of Clinical Psychiatry, Weill Cornell
Institute of Geriatric Psychiatry, Department
of Psychiatry, Weill Cornell Medical College.
George S. Alexopoulos, MD, is S.P. Tobin and
A.M. Cooper Professor, Weill Cornell Medical
College.
Address correspondence to: Jimmy N. Avari,
MD, 21 Bloomingdale Road, White Plains, NY
10605; email: jia9010@med.cornell.edu.
Disclosure: George S. Alexopoulos, MD, has
received fees for non-CME-related services
from Astra Zeneca, Novartis, and Sunovion.
The other authors have no relevant nancial
relationships to disclose.
doi: 10.3928/00485713-20140306-04
Assessment and Management
of Late-Life Depression

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Jimmy N. Avari, MD; Genevieve S. Yuen, MD, PhD; Bassem AbdelMalak, MD;
Nahla Mahgoub, MD; Balkrishna Kalayam, MD; and George S. Alexopoulos, MD
132 | Healio.com/Psychiatry PSYCHIATRIC ANNALS 44:3 | MARCH 2014
CME
L
ate-life depression is a medical
disorder that causes suffering to
patients and their families, exac-
erbates medical illnesses, and increases
mortality and medical costs. Nearly 1%
to 2% of adults aged 65 years and older
are diagnosed with major depressive
disorder. An additional 25% suffer from
signicant depressive symptoms, though
they do not fulll diagnostic criteria for
major depressive disorder proper.
1
The
wide gap between these numbers may,
in part, be accounted for by under-recog-
nition of depressive symptoms and signs
in older patients.
A number of factors contribute to
the underdiagnosis of late-life depres-
sion.
1
Depressive symptoms are often
mistaken as normal aging. Medical
or neurological illnesses may prevent
identication of concomitant depressive
symptoms. Elderly patients have the ten-
dency to report somatic symptoms rather
than psychiatric complaints. Patients
with cognitive impairment may be un-
able to report symptoms of depression.
Identication of late-life depression is
crucial because treatments exist to im-
prove depressive symptoms and signs,
better quality of life, and signicantly
reduce risk of suicide.
1,2
This article dis-
cusses how to assess, diagnose, and treat
late-life depression.
ASSESSMENT AND DIAGNOSIS
Initial Evaluation
To evaluate an elderly patient for
depression, one must obtain psychiat-
ric and medical history and conduct a
mental status and a detailed cognitive
examination. No assessment of an older
psychiatric patient is complete without
a physical examination and a focused
neurological examination. Laboratory
testing should include a comprehensive
chemistry screen, complete blood count,
thyroid stimulating hormone levels, elec-
trocardiogram, serum B12 levels, folate
levels, urinalysis, and drug blood levels
eg, tricyclic antidepressant (TCA)
and mood stabilizer levels. Particular
attention should be given to conditions
that may confound the diagnosis of de-
pression, contribute to depressive symp-
toms, or complicate treatment. Inquiring
about alcohol and substance abuse, cur-
rent medications that can cause depres-
sion, and dementing disorders is par-
ticularly important because these factors
can lead to poor treatment response of
late-life depression. The initial assess-
ment of an elderly patient should include
direct questions about psychosocial fac-
tors (eg, elder abuse, poor environmen-
tal conditions, and changes in the patient
role after the death or disability of a
spouse or partner).
Rating Scales
Standardized rating scales may
complement the initial assessment and
follow-up examination of late-life de-
pression.
1
The Geriatric Depression
Scale is a self-rated instrument used to
screen for depression in cognitively un-
impaired older adults. The Cornell Scale
for Depression in Dementia was devel-
oped for the assessment of depression
in cognitively impaired older patients. It
has been validated both in demented and
non-demented patients. Its ratings are
based on the interviewers clinical judg-
ment after semi-structured interviews of
patients and their caregivers. The Mini-
Mental Status Examination (MMSE)
and the Montreal Cognitive Assessment
(MOCA) are commonly used as screen-
ing tests of cognitive impairment. These
scales provide a method of assessing
severity of depression and cognitive im-
pairment, as well as tracking progress
and response to treatment.
Diagnosis
Late-life depression often occurs in
the setting of medical illness. Somatic
symptoms (ie, changes in sleep and
appetite, loss of energy and fatigue,
changes in memory, and preoccupation
with health) are shared by depression
and many medical illnesses. Therefore,
the diagnosis of late-life depression in
the medically ill should rely mainly
on non-somatic symptoms, including
sadness or downcast mood, persistent
thoughts of death or suicide, anhedo-
nia, hopelessness, worthlessness, guilt,
helplessness, psychomotor agitation or
retardation, and difculty making deci-
sions or starting new projects.
1
Further-
more, depressed elderly patients often
report irritability and fearfulness rather
than sadness.
3

Referrals
Most cases of late-life depression are
treated in primary care settings. How-
ever, patients with psychotic depression,
bipolar disorder, and depression with
suicidal ideation should be referred for
psychiatric consultation and care.
1
Re-
ferral for psychiatric evaluation should
also be considered in cases of late-life
depression with concomitant substance
abuse, double depression (episodes
of major depression superimposed on
dysthymia), severe depression, antide-
pressant-resistant depression, and de-
pression complicated by signicant cog-
nitive impairment or dementia.
Suicide Risk
Elderly Caucasian men have the
highest suicide risk.
2
In older popula-
tions, the incidence of suicide is twice
that of the general population.
2
Most
elderly patients who go on to commit
suicide have visited their primary care
physician in the month prior to suicide.
Assessment of suicide risk in late-life is
The diagnosis of late-life
depression in the medically ill
should rely mainly on
non-somatic symptoms.
PSYCHIATRIC ANNALS 44:3 | MARCH 2014 Healio.com/Psychiatry | 133
CME
complicated by the fact that older adults
who commit suicide allow fewer warn-
ing signs and plan their attempts care-
fully. As a consequence, the suicide
attempt/completed suicide ratio is far
lower than that of younger adults.
4
We
observed that the strongest predictors of
suicide attempts in patients with late-life
major depression are high severity of
depression and disability.
4
Poor social
support and history of serious suicide at-
tempts are predictors of suicidal ideation
in the current episode. Taking these fac-
tors into consideration and using rating
scales to monitor the severity of suicide
risk may be of help. The Columbia Sui-
cide Severity Rating Scale (C-SSRS) is
one such scale.
TREATMENT STRATEGIES
Pharmacotherapy Treatment
The Expert Consensus Guideline
indicates that combined pharmacother-
apy and psychotherapy is the optimal
treatment for late-life major depression
(Figure 1).
1
However, pharmacotherapy
alone is an acceptable treatment. Several
antidepressants are used in the treatment
of late-life major depression. Selective
serotonin reuptake inhibitors (SSRIs) or
serotonin-norepinephrine reuptake in-
hibitors (SNRIs) are viewed as the rst-
line agents in unipolar, non-psychotic,
late-life major depression.
1
The target
doses of SSRIs and SNRIs are approxi-
mately the same as those of younger
adults, although the up-titration period
should be slower. Alternative, second-
line options include bupropion, mir-
tazapine, and TCAs secondary amines
(nortripyline, desipramine). The target
TCA plasma levels (nortriptyline: 60-
120 ng/mL, desipramine: >115 ng/mL)
are similar to those of younger patients,
but they can generally be achieved with
lower dosages. Although denitive stud-
ies are lacking, clinical opinion suggests
that antidepressants should be continued
for 1 year after remission in patients with
a single episode of major depression; 3
years in patients who had two episodes
of major depression; and indenitely in
patients who had three or more episodes
of major depression, suffered from se-
vere depression, or exhibited severe sui-
cidal ideation or behavior.
3

SSRIs
Sertraline is well tolerated by elderly
patients. A placebo-controlled study
showed that sertraline is efcacious in
late-life major depression.
5
However,
sertraline had only a small advantage
over placebo at 8 weeks.
Citalopram is the only SSRI tested in
major depression of old-old patients
(75 years and older). Although there were
no differences between citalopram and
placebo in the overall sample, citalopram
was more efcacious than placebo in pa-
tients with major depression of moderate
and high severity.
6
Escitalopram was not found superior to
placebo in the acute treatment of late-life
major depression.
7
However, escitalopram
was associated with signicantly lower re-
lapse rate (9% versus 33% with placebo)
in a 36-week relapse-prevention study.
7
Paroxetine led to higher remission
rates than placebo in late-life depression
but led to more adverse effects, which
led to discontinuation.
8
A concern relat-
ed to elderly patients on multiple medi-
cations is paroxetines potential drug in-
teractions mediated by inhibition of the
cytochrome P450 2D6.
Vortioxetine is a serotonin (5HT)
reuptake inhibitor. It has weaker af-
nity for the norepinephrine reuptake
transporter, although weaker than the
5HT transporter. Vortioxetine has af-
nity for serotonin (5-HT1A, 5-HT1B,
5-HT1D, 5-HT3A, 5-HT7) and adren-
ergic (1) receptors. The relationship of
vortioxetines binding properties to its
efcacy is yet to be claried. A random-
ized, double-blind, placebo-controlled,
duloxetine-referenced study showed
that vortioxetine was more efcacious
than placebo in late-life depression and
had a lower rate of adverse effects than
duloxetine.
9
Animal studies and human
studies have suggested that vortioxetine
may improve some cognitive functions.
However, the relevance of these effects
in late-life depression remains unclear.
Figure 1. Treatment algorithm for unipolar late-life major depression. ECT = electroconvulsive therapy;
SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor;
TCA = tricyclic antidepressant.
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SNRIs
Venlafaxine-XR is often used as a
rst-line medication treatment for late-
life depression.
1
Studies showed no dif-
ference in remission rates compared to
SSRIs or TCAs.
10
However, venlafaxine
may be less tolerated than SSRIs.
10

Duloxetine has adequate efcacy and
tolerability in the treatment of late-life
depression, regardless of comorbid med-
ical conditions.
11
TCAs
Nortriptyline is efcacious in the
acute treatment of late-life depression.
12

A randomized, controlled study by
Reynolds et al. showed that nortriptyline
alone and in combination with interper-
sonal psychotherapy is superior to pla-
cebo in preventing recurrence of late-life
major depression.
13
MAOIs
Transdermally administered sele-
giline has been found efcacious and
well-tolerated in younger adults with
major depression.
14
A small dose (6 mg)
of transdermally administered selegiline
has been found efcacious and does not
require a monoamine diet. There are no
studies of transdermal selegiline in late-
life depression.
Heterocyclics
Bupropion is a second-line treatment
for nonpsychotic late-life major depres-
sion.
1
Studies have shown conicting
results when comparing it to SSRIs and
TCAs in this population.
15
Placebo-con-
trolled studies have shown inconsistent
efcacy of bupropion in reducing late-
life depression symptoms and in remis-
sion rates.
15
A study comparing the efcacy and
tolerability of mirtazapine to parox-
etine in late-life depression found that
mirtazapine produced somewhat faster
symptomatic relief and was better tol-
erated.
16
This effects may be related to
mirtazapines effects on anxiety and in-
somnia. Therefore, mirtazapine may be
an option for patients with prominent
such symptoms.
16
NON-PHARMACOLOGIC
TREATMENTS
Psychotherapies
A combination of psychotherapy with
pharmacotherapy is a rst-line treatment
for late-life major depression, but psy-
chotherapy alone is an acceptable treat-
ment in syndromes of mild severity.
1
Psychotherapy is strongly indicated in
late-life depressive episodes associated
with a stressor. Unlike pharmacological
treatment, psychotherapy can address
concerns specic to the late-life popula-
tion (eg, living under chronic stress due
to disability, cognitive limitations, role
changes, and family tension related to
caregiving. A meta-analysis showed no
difference in efcacy between pharma-
cotherapy and psychotherapy (cogni-
tive-behavioral therapy, interpersonal
psychotherapy, psychodynamic therapy
and others) in late-life depression.
17
Psy-
cho-education, family counseling, visit-
ing nurse services, bereavement groups,
and senior citizen center attendance may
provide added benet.
1
Psychotherapies
developed for depressed elders are dis-
cussed in greater detail in the article by
McGovern et al. in this issue.
Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is
particularly useful in the acute treat-
ment of late-life depression because of
its high efcacy and fast symptom re-
lief.
18
ECT is an appropriate rst-line
treatment for patients suffering from
psychotic depression, severe depres-
sion, acute suicide risk, refusal of food
and drink, and for patients who can-
not tolerate antidepressants due to co-
morbid medical illnesses.
1,18
A large,
prospective study demonstrated that
depressed old-old patients aficted by
medical illnesses and cognitive impair-
ment responded equally or better to
ECT than their younger counterparts.
19
Seizure threshold increases with age,
which often decreases the need to
switch from suprathreshold right uni-
lateral to suprathreshold bilateral ECT.
The positive response of older adults
to right unilateral ECT is of particular
importance, as this group may be more
vulnerable to continual confusion when
treated with bilateral ECT.
19
Older
adults are already more likely to expe-
rience a more severe post-seizure de-
lirium and a more prolonged period of
confusion. ECT should also be strongly
considered for older patients with de-
pression of at least moderate severity
who have failed two adequate trials of
antidepressants.
18
Transcranial Magnetic Stimulation
Repetitive transcranial magnetic
stimulation (rTMS) has been approved
for the treatment of adult depression. It
provides a well-tolerated non-pharma-
cologic treatment alternative for major
depression that has failed to respond to
one antidepressant.
20
Its efcacy in late-
life depression is yet to be established.
Deep Brain Stimulation
Deep brain stimulation (DBS) of the
ventral anterior internal capsule and
ventral striatum has been approved by
U.S. Food and Drug Administration
(FDA) for the treatment of obsessive
compulsive disorder. Small, open-label
studies have shown that DBS may lead
to sustained remission in 40% to 60%
of younger adults with treatment resis-
A meta-analysis showed no
difference in efcacy between
pharmacotherapy and
psychotherapy in
late-life depression.
PSYCHIATRIC ANNALS 44:3 | MARCH 2014 Healio.com/Psychiatry | 135
CME
tant depression.
20
Different locations of
DBS leads have been employed, includ-
ing the subcallosal cingulate white mat-
ter, the ventral anterior internal capsule,
the ventral striatum, the nucleus accum-
bens, the inferior thalamic peduncle, and
the habenula. There have been no DBS
studies of depressed older adults to date.
SPECIAL POPULATIONS
Unipolar Psychotic Major
Depressive Disorder
Both ECT and a combination of an-
tidepressants with antipsychotic drugs
are acceptable treatments for late-life
psychotic depression (Figure 1). ECT
may lead to symptom relief and/or re-
mission in up to 90% of patients with
psychotic depression.
18
Treatment with
olanzapine plus sertraline was associ-
ated with higher remission rates than
olanzapine plus placebo in a 12-week
study.
21
Approximately 42% of subjects
who underwent combination therapy
were in remission at their last assess-
ment, compared with 24% of subjects
treated with monotherapy. Combination
therapy was equally effective in both
younger and older ( 60 years) adults.
Both age groups had signicant in-
creases in cholesterol and triglycerides,
but statistically signicant increases
in glucose occurred only in younger
adults. Younger adults gained signi-
cantly more weight than older subjects.
Other combinations of antidepressants
and antipsychotic drugs may be efca-
cious in late-life psychotic depression.
However, adequately controlled studies
are not available.
Dysthymic Disorder
Dysthymic disorder may be treated
with antidepressants and psychother-
apy, but antidepressants alone or psy-
chotherapy alone are also acceptable
choices.
1
SSRIs are considered the rst-
line drug treatment for dysthymic disor-
der. SNRIs or bupropion are reasonable
second-line choices.
Depression Associated with an
Adverse Life Event
The Expert Consensus Guideline
recommends psychotherapy alone or
in combination with antidepressants in
late-life depression associated with a
stressor.
1
Psychotherapy can improve the
patients coping skills and allow them to
better address adversity. The addition of
antidepressants to psychotherapy should
be considered in severe or long-lasting
depression after an adverse life event.
Although antidepressants are effective
in depression associated with an external
stressor, the best outcomes are obtained
when antidepressants are combined with
a psychosocial intervention.
1
Antidepressant-Resistant
Depression
Inadequate response to antidepres-
sants, dened as little to no response
after an acceptable dose has been main-
tained for an adequate duration, war-
rants switching to another antidepres-
sant (Figure 1). If the patient has a
partial response to the initial antidepres-
sant, The Expert Consensus Guideline
recommends addition of an augmenting
agent.
1
Appropriate augmentation for
SSRI partial responders are bupropion,
lithium, or nortriptyline; for TCA or bu-
propion partial responders, lithium or
SSRI; and for venlafaxine XR partial
responders, lithium.
1
The combination
of olanzapine plus uoxetine is effec-
tive in treatment-resistant depression
of adults.
22
Moreover, aripiprazole and
quetiapine XR have an FDA indication
for augmentation therapy of antidepres-
sants in major depression.
Non-pharmacological biological
treatments for antidepressant-resistant
depression include: ECT, rTMS, va-
gal nerve stimulation, and deep brain
simulation. Several studies have dem-
onstrated the efcacy of ECT in treat-
ing these patients, as mentioned above.
rTMS and DBS are both FDA-approved
for the treatment of medication-refracto-
ry depression in adults, but neither has
been tested in elderly populations. Vagal
nerve stimulation is FDA-approved for
treating medication-refractory depres-
sion in adults and may lead to remission
in 30% to 40% of patients,
20
but it has
not been tested in older adults.
Residual Insomnia
For depressed elderly patients who
experience residual insomnia after im-
provement of depression, the Expert
Consensus Guideline recommends ei-
ther an increase of the antidepressant
dosage or addition of a sedating anti-
depressant (eg, trazodone).
1
Adjunctive
treatment with zolpidem, zaleplon, or
mirtazapine can be useful for patients
with severe insomnia. Benzodiazepines,
especially long-acting benzodiazepines,
should be avoided because of increased
risk of falls, memory impairment, para-
doxical agitation, and risk of addiction.
Residual Anxiety
For anxiety persisting after improve-
ment of depressive symptoms and signs,
the Expert Consensus Guideline recom-
mends using the maximum therapeutic
dose of the antidepressant.
1
Anxiolytic
agents should be avoided, especially
in patients with dementia or signicant
cognitive impairment.
NEUROBIOLOGICALLY BASED
SUBTYPES OF LATE-LIFE
DEPRESSION
Depression-Executive Dysfunction
Syndrome
We reported that abnormal execu-
tive functions predict poor or delayed
response of late-life depression to anti-
depressants, high relapse and recurrence
rates, and disability disproportional to
the severity of depression.
2
These nd-
ings led us to propose that depression
with executive dysfunction (DED) is a
distinct clinical entity. The clinical pre-
sentation of DED is characterized by
psychomotor retardation, apathy, and
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lack of insight.
23
DED patients have
decits in abstracting, planning, initi-
ating, and sequencing their behavior.
Structural and functional MRI studies
of depressed elderly patients revealed
abnormalities in cortico-striato-pallido-
thalamo-cortical pathways consistent
with the clinical presentation of DED.
2

Given the adverse clinical outcomes
of DED, testing executive function
should be a part of the assessment for
late-life depression. Simple bedside
tests may be used to screen for execu-
tive dysfunction, such as a verbal uen-
cy test (ie, ask patient to recall as many
items one can buy in a supermarket in
1 min; at least 15 should be given by
a depressed elderly patient without ex-
ecutive dysfunction) or the Stroop Color
Word test. Abnormal performance in
each of the tests has been found to be as-
sociated with poor response of late-life
major depression to antidepressants.
2
More details on cognitive abnormalities
and on the cognitive examination of de-
pressed older adults are discussed in the
articles by Morimoto et al. and Manning
et al. in this issue.
Patients with DED may benefit
from rigorous pharmacological treat-
ment, close follow-up, and targeted
psychotherapies. Our PROSPECT
study documented that DED patients
have better remission and response
rates with Depression Care Man-
agement than usual care provided in
general medical practices.
24
Problem-
solving therapy modified by Alexo-
poulos and Arean
25
led to remission in
38% of DED patients and was more
effective than supportive therapy.

Dopamine receptor 3 (D3) agonists
have been proposed as a treatment for
DED.
26
Dopaminergic systems partici-
pate in the regulation of striatofrontal
neural systems and could potentially
have an antidepressant effect. Animal
models have shown that D3 agonists
reduce stress-induced anhedonia, in-
crease intracranial self-stimulation,
and enhance stimulus-reward learning.
These responses are similar to those of
classical antidepressants. D3 agonists
are used in the treatment of motor symp-
toms of Parkinsons disease. The D3
agonist pramipexole was found to im-
prove depressive symptoms in Parkin-
sons disease patients. Pramipexole has
been found as effective as uoxetine and
more effective than placebo in young
patients hospitalized for major depres-
sion.
26
However, randomized, controlled
trials in depressed elderly patients with
executive dysfunction are lacking.
Vascular Depression
The vascular depression hypothe-
sis, in its current form, was proposed in
1997 and postulated that cerebrovascu-
lar disease can predispose, precipitate,
or perpetuate a depressive syndrome
in older adults.
27
The vascular depres-
sion hypothesis is supported by nd-
ings suggesting that: 1) cerebrovascular
disease or risk factors may lead to late-
life depression syndromes; 2) the high
frequency of depression in patients with
hypertension, diabetes, coronary artery
disease, and vascular dementia; 3) the
frequent occurrence of silent stroke
and white matter hyperintensities in
late-life depression; and 4) the associa-
tion of depression with lesions impair-
ing the integrity or regulation of pre-
frontal systems.
27
Patients with vascular
depression often have impairment of ex-
ecutive functions, symptoms and signs
similar to those of median frontal lobe
syndrome (ie, psychomotor retardation,
apathy, impaired insight, signicant dis-
ability), and poor response to classical
antidepressants. Neuroimaging can of-
fer information on the extent of white
matter hyperintensities; most are caused
by cerebrovascular lesions. High vol-
ume of white matter hyperintensities
has been associated with poor response
to antidepressants.
2

Management of vascular depression
should include careful control of hyper-
tension and hypercholesterolemia and
use of aspirin or other anticoagulants
in patients with atrial brillation. Aug-
mentation of uoxetine with the calcium
channel blocker nimodipine resulted in
more effective treatment of depression
and lower recurrence rates.
28
INFLAMMATION MODEL IN LATE-
LIFE DEPRESSION
Aging results in increased peripheral
immune responses, impaired peripheral-
CNS immune communication, and a
shift of the CNS into a pro-inammato-
ry state.
29
In addition, chronic comorbid
disease-related inammatory processes
are more prevalent in older adult popu-
lations. Combined aging-related and
chronic disease-related changes may
promote abnormalities in emotional and
cognitive brain networks and lead to
late-life depression. Limited data sug-
gest that some anti-inammatory agents
may have antidepressant properties. A
randomized, controlled trial demon-
strated that iniximab (a tumor necrosis
factor antagonist) was specically effec-
tive for the treatment of antidepressant-
nonresponsive patients who had high
baseline inammatory markers.
30
We
conducted a proof of concept, open-
label study of minocycline. This anti-
biotic crosses the blood brain barrier,
modulates the N-methyl-D-aspartate
glutamatergic receptor, and has anti-
inammatory action. Depressed, elderly
patients who remained symptomatic af-
ter at least one adequate antidepressant
trial received minocycline augmentation
(target dose 200 mg daily) for 8 weeks.
High volume of white matter
hyperintensities has been
associated with poor response
to antidepressants.
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Preliminary analysis showed that three
of the 11 patients who have completed
the study achieved remission.
CONCLUSION
Late-life depression is a complex
disorder with signicant cognitive and
medical comorbidity and an alarm-
ingly high risk of suicide. Identifying
and diagnosing late-life depression is
challenging but can be accomplished
through appropriate screening and a
comprehensive assessment of psycho-
pathology, cognition, medical status,
and the environment of the older patient.
Several treatment modalities are current-
ly available for late-life depression. Poor
response to antidepressant treatments is
common, and relapse is high. However,
clinical research continues to elucidate
the neurobiology of late-life depression
syndromes and to guide the develop-
ment of novel biological interventions
and targeted psychotherapies.
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