Diagnosis and Management of Late-Life Unipolar Depression - UpToDate

10/04/2020 Diagnosis and management of late-life unipolar depression - UpToDate
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Diagnosis and management of late-life unipolar

depression
Authors: Randall T Espinoza, MD, MPH, Jürgen Unützer, MD, MPH
Section Editors: Peter P Roy-Byrne, MD, Kenneth E Schmader, MD
Deputy Editor: David Solomon, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2020. | This topic last updated: Nov 22, 2019.
INTRODUCTION
The term late-life depression includes both aging patients whose depressive disorder presented in
earlier life, and patients whose disorder presents for the first time in later life. Depressive illness in
the older population is a common and serious health concern that is associated with comorbidity,
impaired functioning, excessive use of health care resources, and increased mortality (including
suicide) [1].
Late-life depression remains underdiagnosed and inadequately treated [2-5]. In the United States,
older men, especially older African Americans and Hispanics, are at even greater risk of
unrecognized depression [6-8]. The public health consequences of inadequately treated
depression in late life will increase over time as the population continues to age.
Over 80 percent of mental health treatment for depressed older adults is delivered in the primary
care setting. Depression often goes undiagnosed in primary care [9], and is often left untreated,
even when diagnosed [10]. Recognition and management of late-life depression is an important
responsibility for the primary care clinician. Either pharmacotherapy or psychotherapy can benefit
patients [1].
This topic reviews the epidemiology, diagnosis, and treatment of late-life unipolar depression. The
clinical features, assessment, diagnosis, and treatment of unipolar major depression in adults age
18 to 65 years, are discussed separately. (See "Unipolar depression in adults: Clinical features"
and "Unipolar depression in adults: Assessment and diagnosis" and "Unipolar major depression in
adults: Choosing initial treatment" and "Unipolar depression in adults: Choosing treatment for
resistant depression".)
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EPIDEMIOLOGY
Depression is not a normal consequence of aging [11,12]. Sadness and grief are normal
responses to life events that occur with aging such as bereavement; adjustment to changes in
social status with retirement and loss of income; transition from independent living to assisted or
residential care; and loss of physical, social, or cognitive function from illness (see "Grief and
bereavement in adults: Clinical features"). Despite these losses, healthy independent community-
dwelling elderly in the United States have a lower prevalence rate of clinical depression than the
general adult population (figure 1) [13].
Rates of depression for community-dwelling older adults range from 2 percent (for patients in
community settings who meet strict diagnostic interview criteria) to about 10 percent for patients
with minor depression [14]. Cultural factors [15] as well as variations in methods of assessment
lead to significant variations in reported prevalence. Rates of depression are higher for older
adults with comorbid medical illness and in general medical settings. Hospitalized geriatric
populations have prevalence rates of depression over 30 percent, and patients with stroke,
myocardial infarction (MI), or cancer have rates over 40 percent (figure 1) [16-18].
Although prevalence of depression in the older healthy population is lower than in comparable
younger groups, incidence rates may not differ. A cohort study of 5600 community dwelling
persons in the Netherlands, aged 56 or older (mean age 70 years at baseline) and followed for
eight years, found the incidence of depressive syndromes (major depression and dysthymia) to be
7 per 1000 person years [19]. Most depressive episodes occurred in persons with a prior history of
depression, with a recurrence rate of 25.5 per 1000 person years. Clinically significant but
subthreshold depressive symptoms occurred at twice the rate of depressive syndromes.
The true incidence of depressive disorders in the oldest-old (>85 years old) may be
underestimated. This group may have an increased prevalence of depressive symptoms, although
few epidemiologic studies have included participants of these ages [20,21].
Risk factors — Patients who experience their first episode of depression later in life are less likely
to have a family history of depression or other major mental disorder than patients whose first
episode occurred earlier in life. This difference suggests that genetic or familial factors are less
likely to have a role in late-onset depression [3,22].
Risk factors for late-life depression include [23]:
● Female sex
● Social isolation
● Widowed, divorced, or separated marital status
● Lower socioeconomic status
● Comorbid general medical conditions
● Uncontrolled pain
● Insomnia
● Functional impairment
● Cognitive impairment
Depression occurring in the course of adverse life events was previously termed "reactive
depression" and felt to be an expected consequence of stress or trauma. Clinical major
depression should be addressed as a serious medical condition regardless of life precipitants
because treatment can be effective.
Insomnia is not only a risk factor for developing dysthymia and depression in older adults, but
persistence of insomnia has been associated with persistence of depression [24]. Additionally, a
history of sleep disturbance was an independent risk factor for recurrence of depression in older
adults in remission from depression [25]. Further studies are indicated to determine whether
insomnia, rather than a symptom of depression, is a comorbid disorder in at least some older
patients, and whether treatment for insomnia would improve depression response or prevent
recurrent depression.
Nursing home residence — As many as 50 percent of nursing home residents are depressed.
A study of 634,060 nursing home residents 65 years and older found that during their first year, 54
percent had physician-diagnosed depression [26]. Severe cognitive impairment was associated
with lower rates of depression; such impairment may interfere with detecting depression.
Female gender — The prevalence of depression is higher in women across all age groups.
Several factors may account for the disproportionate prevalence of depression in older women:
greater susceptibility to depression, greater persistence of depression after its onset, and lower
mortality [27]. To some extent, this may also be an artifact of how depression is defined and
symptoms are elicited [28-30]. Men are more likely to present with anger, irritability, anhedonia,
withdrawal or apathy, and alcohol abuse, and less likely to acknowledge sadness or psychological
symptoms [31]. With increasing age, the gender gap in depression prevalence narrows [29]. Men,
with a higher prevalence of vascular risk factors, may present with a depression subtype known as
vascular depression (see 'Vascular depression' below).
General medical illness — The risk of depression in physically ill elderly increases with:
● Recent onset of physical illness

● Greater severity of physical illness
● Functional disability and limited mobility
● Poorly treated pain
● Multiple illnesses
Depressed mood may be the first symptom of a number of medical conditions affecting the elderly
including stroke, diabetes, cancer, hypothyroidism, and coronary disease [32].
Impact — Depression amplifies disability and lessens quality of life. Late-life depression is
associated with increased office and emergency department visits, increased drug use and cost
for both prescription and over-the-counter medications, higher risk for use of alcohol or illicit drugs,
increased length of inpatient stay, and overall higher costs of care [33,34]. Depression in late life
also tends to be a recurrent or persistent condition and adversely impacts both medical and
psychiatric morbidity and mortality [28,35].
Medical comorbidity — Treatment of depression can have beneficial effects on health

outcomes in patients with chronic medical conditions such as chronic pain, diabetes, and
osteoarthritis [36,37]. The impact of depression on medical mortality is being recognized and
quantified:
● Depression onset in post-MI patients was associated with a fourfold increase in death [38].
● Patients who developed depression after a stroke were 3.4 times more likely to have died
over a 10-year follow-up period [39,40].
● Depression at the time of admission to a nursing home increased one year mortality [41].
● A modified diagnosis of major depressive disorder and a past history of depression

independently predicted in-hospital death with an odds ratio of 7.8 after controlling for severity
of illness [42].
Treatment of depression may also impact medical mortality. A decrease in overall risk of death at
five years, attributed to fewer cancer deaths, was seen in patients aged 60 and older with major
depression who were randomly assigned to an intervention to improve depression treatment
(involving a care manager), compared to patients assigned to a control group receiving usual care
[43].
Psychiatric comorbidity — Comorbidity of depressive illness with other psychiatric

syndromes such as anxiety, somatization, and substance abuse may affect overall treatment
response and increase the risk of relapse and recurrence [3,23,44]. Comorbid substance abuse
with alcohol, prescription pain, or hypnotic medications is under recognized, and increases the risk
of falls, accidents, and cognitive impairment [4,23,44].
Comorbidity with anxiety may be a particular problem in the elderly population. The presence of
anxiety with depression, especially if somatic complaints are over emphasized or primarily
addressed, can lead to a missed diagnosis or inappropriate treatment with anxiolytic, hypnotic, or
pain medications [4,44,45].
Suicide risk — Depression is a major risk factor for suicide in the elderly, who account for
about 13 percent of the United States population, but for nearly 24 percent of all completed
suicides [46]. Elderly patients attempt suicide less often than younger patients, but are more
successful at completion [47]. Elderly men have the highest suicide rate: 28.9 per 100,000 in 2004
[48]. White men age 85 or older have the highest rate of completed suicide, 55 per 100,000 [46].
Most elderly suicide victims were in their first episode of depression and had seen a physician
within the last month of life.
Particular care should be paid to the elderly patient who might be at acute risk for suicide and
presents with the following: hopelessness, insomnia, agitation or restlessness, impaired
concentration, active psychosis, active alcohol use or intoxication, and untreated unremitting pain.
(See "Suicidal ideation and behavior in adults".)
Other risk factors for suicide include [47,49,50]:
● Comorbid physical illness

● Chronic and inadequately treated pain
● Terminal illness or worsening of physical illness
● Widowhood and social isolation
● Personality disorders
● Prior suicide attempt
● Family history of suicide
Compared with usual care, collaborative care interventions for depressed older primary care
patients can lower rates of suicidal ideation [51,52]. (See 'Collaborative care' below.)
Subsequent dementia — Late life depression is associated with an increased risk of

subsequently developing dementia:
● A meta-analysis of 23 prospective, community based, observational studies included more

than 49,000 subjects who did not have dementia at baseline and were followed for a median
of five years [53]. The risk of all-cause dementia was greater in subjects with late life
depression than the nondepressed controls (risk ratio 1.9, 95% CI 1.7-2.0). Specifically, late
life depression was associated with an increased risk of Alzheimer disease and vascular
dementia, and the risk of vascular dementia was greater than the risk of Alzheimer disease.
The elevated risk for all-cause dementia persisted in analyses that included only those
studies (n = 17) that adjusted for potential confounders (risk ratio 1.6, 95% CI 1.4-1.8).
● A retrospective study of medical records (n >13,500 individuals who did not have dementia at
baseline) over a six year follow-up period found that after adjusting for potential confounds,
the risk of all-cause dementia was increased 70 percent in subjects who had late life
depressive symptoms (hazard ratio 1.7, 95% CI 1.5-1.9) [54]. Specifically, depression was
associated with an increased risk of Alzheimer disease and vascular dementia.
Late life depression may reflect a prodromal stage of dementia or may act as an independent risk
factor for dementia.
In addition, dementia may give rise to episodes of depression. (See 'Alzheimer disease and other
dementias' below.)
PATHOGENESIS
The field of neuropsychiatry is providing insight into the understanding of late-life depression.
Damage to frontal subcortical circuitry, specifically the striato-pallido-thalamo-cortical pathways,
due either to neurodegeneration or cerebrovascular disease, is implicated in some subtypes of
late-life depression [55-58]. (See 'Vascular depression' below.)
Subclinical cerebrovascular disease may also influence the susceptibility to, and expression of,
depression. Cerebral atrophy, subcortical deep white matter [59], and periventricular ischemic
lesions, commonly seen on brain imaging, may be implicated. Other radiologic findings in late-life
depression are increased ventricular brain ratios and decreased volumes in specific brain regions
[60-62].
CLASSIFICATION
The effects of age of onset, changes in the aging brain, and the presence of medical comorbidity
influence the type and expression of depression as well as treatment responsiveness. Some
patients may have clinically significant depressive symptoms but do not totally fulfill the criteria for
syndromal major depression as defined by the Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition (DSM-5) (table 1) [63]. (See "Unipolar depression in adults: Assessment
and diagnosis".)
Major depression — The DSM-5 criteria for major depression (table 1) are identical for both
elderly and younger patients [63]. Of note, major depression in later life is more likely to become
chronic and recovery may be more transient, leading to frequent relapses. The risk of relapse and
chronicity appears heightened by extensive comorbidity.
Elderly patients with major depression may have cognitive impairment that develops coincident
with or after the onset of mood symptoms, a condition previously termed pseudodementia and
now referred to as dementia syndrome of depression, because the cognitive deficits are
demonstrable. Antidepressant treatment can resolve the cognitive and mood symptoms of these
patients. By contrast, mild to moderate depression in patients with Alzheimer disease may not
respond to antidepressant therapy (eg, sertraline or mirtazapine) [64], or if depressive symptoms
do improve [65-67], the primary cognitive deficits of Alzheimer disease persist or become worse. It
is worth noting that patients with cognitive impairment secondary to major depression may be at
higher risk of converting to an irreversible dementia syndrome such as Alzheimer disease [65-69].
Persistent depressive disorder (dysthymia) — Elderly patients should fulfill the same DSM-5
criteria for persistent depressive disorder (table 2) as younger patients [63]. Dysthymia manifests
with depressive symptoms that occur on the majority of days for at least two years. Elderly
patients with late onset dysthymia have a higher prevalence of cardiovascular disease, but are
otherwise similar to older patients with late onset major depression [70]. Patients with persistent
depressive disorder are at greater risk of developing major depression, so-called "double-
depression," and may be particularly treatment resistant.
Minor depression — Minor depression (subsyndromal depression) is diagnosed in patients with

depressive syndromes that do not meet DSM-5 criteria for major depression (table 1) or persistent
depressive disorder (dysthymia) (table 2) because of too few symptoms or the duration of
symptoms is too short. In DSM-5, minor depression is classified as “other specified depressive
disorder,” followed by the reason that the depressive syndrome does not meet criteria for a
specific disorder such as major depression or persistent depressive disorder [63]. Reasons
include “depressive episode with insufficient number of symptoms” or “short duration depressive
episode.”
Minor depression in late life is more prevalent than major depression, and minor depression is
important in the elderly population because these patients suffer disease burdens comparable to
patients with major depression, including poorer health and social outcomes, functional
impairment, and higher health care utilization and treatment costs [71-74].
In addition, patients with minor depression are at high risk for subsequently developing major
depression, and may develop suicidal ideation. In one study, patients with minor depression, aged
60 years and older, had a 6-fold risk of developing major depression at one year compared to
patients without depression [74].
The clinical features, diagnosis, and treatment of minor depression in mixed age populations are
discussed separately. (See "Unipolar minor depression in adults: Epidemiology, clinical
presentation, and diagnosis" and "Unipolar minor depression in adults: Management".)
Psychotic depression — Unipolar major depression with psychotic features (delusions or

hallucination) is a severe subtype of unipolar major depression (major depressive disorder), which
occurs at least as often in older patients as younger patients [75-78]. The epidemiology, clinical
features, assessment, diagnosis, treatment, and prognosis of unipolar psychotic depression are
discussed separately. (See "Unipolar major depression with psychotic features: Epidemiology,
clinical features, assessment, and diagnosis" and "Unipolar major depression with psychotic
features: Acute treatment" and "Unipolar major depression with psychotic features: Maintenance
treatment and course of illness".)
Vascular depression — Cerebrovascular disease may increase an older person's vulnerability

toward development of depression through a variety of neurobiological mechanisms [55,57].
Depression may develop after an acute cerebrovascular event (termed "post-stroke depression"
[PSD]) [79] or may develop in association with chronic ischemic changes in the brain (termed
"vascular depression") [57,80]. Two factors important in the development of PSD are lesion
location and time from stroke. Patients with left hemisphere lesions, especially of the left prefrontal
cortex, tend to have increased frequency and severity of depression. The greatest risk period from
time of stroke appears to be the first two years, with peak prevalence of PSD occurring within the
first three to six months [79].
The importance of chronic ischemic cerebral changes is only recently recognized. A study of
depressed patients with and without MRI abnormalities demonstrated that positive MRI findings
correlated with older age at onset of depression, vascular comorbidity, greater psychomotor
slowing or Parkinsonism, anhedonia, increased functional impairment, and lower incidence of
psychosis [80,81]. Another study found that patients with late onset depression and
cerebrovascular risk factors, compared with other late onset patients, had more cognitive
impairment and disability, more psychomotor retardation, less agitation, less guilt, and less insight
into their illness [57]. Depressed patients with vascular risk factors have been found to be at
higher risk of developing vascular dementia [82]. (See "Etiology, clinical manifestations, and
diagnosis of vascular dementia".) Preliminary data suggest that these patients may preferentially
respond to nonstandard antidepressant therapy, including older antidepressants, combination
therapies, or electroconvulsive therapy [55,79,83].
The syndrome of depression with executive dysfunction may also be related to cerebrovascular
disease or age-related neurodegeneration [84,85]. Patients present with frontal executive
impairment manifested by difficulties with motivation, organization, planning, sequencing, and
abstracting. They typically exhibit anhedonia and apathy rather than sadness, and have cognitive
impairment with psychomotor retardation [85,86].
Alzheimer disease and other dementias — The development of depression as a complication of

Alzheimer disease is increasingly recognized. Presentation and treatment responsiveness may
significantly differ from early onset and other types of depression [87,88]. A proposal from the
American Association for Geriatric Psychiatry suggests revised diagnostic criteria for depression in
Alzheimer disease (table 3) [89]. Additionally, depression is a common complication in many other
dementia syndromes including Parkinson Dementia, Lewy Body dementia, Frontotemporal
dementia, and Huntington's dementia. (See "Management of neuropsychiatric symptoms of
dementia".)
DIAGNOSIS
Assessing patients to make the diagnosis of depression in late life is challenging, especially in the
physically frail elderly. Multiple factors complicate the diagnosis of depression in the elderly:
● Concurrent medical illness with overlapping symptoms of depression (fatigue, psychomotor

slowing, loss of appetite, sleep disturbance, lack of sexual interest, memory complaints)
● Medication side effects overlapping depression symptoms
● Impaired communication skills in the elderly
● Patient presentation with multiple somatic complaints
● Lack of time in the clinical exam to evaluate psychological problems in patients with complex
medical issues
● Therapeutic nihilism regarding depression on the part of the patient, family, or provider
● Patient's reluctance to acknowledge psychological distress due to perceived stigma of mental

illness [90]
Depression diagnosis with medical comorbidity — A few clues are helpful in diagnosing late-
life depression in the setting of medical comorbidity. Depression should be considered when the
following are present:
● Mood or somatic symptoms out of proportion to what is expected

● Poor response to standard medical treatment
● Poor motivation to participate in treatment
● Lack of engagement with care providers
Depression diagnosis in the frail elderly — Dysphoric mood may be less reliable as an
indicator of depression in the oldest old (>85 years of age) [31]. Depression criteria in the frail
elderly should emphasize a change in mood or interest with at least two weeks duration, non-
physical symptoms, and social regression or incapacity. Physical symptoms used to support the
diagnosis of depression should occur with or worsen after mood symptoms, and should be out of
proportion to what is expected of the illness or usual treatments. Depression is less likely to be
present if the patient responds to affection from family and caregivers, retains humor, looks
forward to visits, and accepts assistance and care.
Screening instruments — Several screening instruments have been developed and validated for
use in primary care and other settings [91]. As screening tools, these should not be the sole basis
for diagnosing depression. When patients screen positive with an instrument, a clinical diagnostic
interview is necessary to determine if criteria for major depression are met and if treatment is
indicated.
Several screening tools are available (table 4). The instruments vary by whether they are self- or
interviewer-reported, applicable to patients with cognitive or language barriers, or validated for
monitoring treatment response. These tools are:
● Two question screener — A two question screener is easily administered and likely to identify
patients at risk if both questions are answered affirmatively [92,93]. The questions are:
• "During the past month, have you been bothered by feeling down, depressed or
hopeless?"
• "During the past month, have you been bothered by little interest or pleasure in doing
things?"
A similar instrument, the Patient Health Questionnaire 2 (PHQ-2), was evaluated in a United
States sample of over 8,000 non-institutionalized adults aged 65 years and older [94]. Compared
with DSM-5 criteria for major depression, the PHQ-2 had a sensitivity of 100 percent and
specificity of 77 percent in this population; specificity increased with age, male gender, and varied
with racial and ethnic groups.
● The Geriatric Depression Scale – This self-report instrument has been studied in multiple
settings [95,96]. A five-item version demonstrated good receiver operating characteristics
across the full spectrum of elderly populations [96]. The five items are:
• Are you basically satisfied with your life?
• Do you often get bored?
• Do you often feel helpless?
• Do you prefer to stay at home rather than going out and doing new things?
• Do you feel pretty worthless the way you are now?
Two out of five depressive responses ("no" to question 1 or "yes" to questions 2 through 5)
suggests the diagnosis of depression [97].
● The PHQ-9 – This was developed specifically for use in primary care settings and has
demonstrated ease, validity, and reliability (table 5) [98]. It covers all nine DSM-5 criteria for
major depression and can be used to help establish a diagnosis of major depression. The
PHQ-9 was shown to be a reliable measure of depression treatment outcomes in a large
study of older adults [99]. The tool can be used to assess response to treatment in individual
patient care.
● Cornell Scale for Depression in Dementia – This incorporates both observer and informant
based information and is helpful in evaluating cognitively impaired patients for depression
[100].
● The Center for Epidemiologic Studies Depression Scale – This is one of the most common
instruments applied in community studies and commonly used in primary care settings
[101,102].
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The general screening of depression is discussed separately. (See "Screening for depression in
adults".)
TREATMENT
Successful treatment of depression in late life is dependent upon several factors: addressing
comorbid conditions, tailoring pharmacologic or other interventions to the individual patient,
monitoring therapy for side effects and effectiveness, and assuring close follow-up. Consultation
with a mental health specialist should be considered for patients who have failed multiple trials of
antidepressants or who have a preference for non-pharmacologic treatment.
A complete history will guide treatment decisions. Aspects of the history of special importance in
managing depression in the elderly are:
● Assessment for suicidality, including ideation and plan (lethality, intent, and means). Acute
suicidal ideation requires urgent psychiatric referral [51].
● Assessment for psychotic symptoms, hopelessness, insomnia, and malnutrition.
● Determination of whether the patient is using medication(s) with depressant side effects
(benzodiazepines, central nervous system depressants, opiates, other pain medications) or is
abusing alcohol.
● Consideration of other medical conditions commonly associated with depressive symptoms,

particularly unrecognized thyroid disease, or diabetes. Additionally, pain syndromes can be a
barrier to treatment response in depression and should be treated along with the depression
[103].
● Determination of history of prior depressive episodes, age of depression onset, prior drug
therapy and outcome, and length of prior remission if achieved.
● Determination of a family history of depression and family response to medication. Older

patients with mild depressive symptoms and first degree relatives with confirmed depression
diagnosis have a 1.5 to 3 times greater risk for depression than the general population [104].
First-line treatment of depression consists of psychotherapy and somatic therapy (medication or

electroconvulsive therapy). A meta-analysis of 89 controlled studies involving older adults with
depression of varied severity (major depression, minor depression and dysthymia) found that well-
designed randomized studies were limited, but that the overall effect size of either psychotherapy
or medication was moderate to large, and roughly equivalent [105]. The choice of treatment will
depend upon the severity, type, and chronicity of the depressive episode, contraindications to
medication, treatment access, and patient preference. Psychotherapy and pharmacotherapy may
be used singly or in combination [106]. For moderate to severe forms of depression, we
recommend pharmacotherapy. For chronic forms of depression, the combination of

pharmacotherapy and psychotherapy may be most effective [107].
Several studies suggest that treatment programs that offer a choice of medication and/or
psychotherapy in primary care, often combined with patient outreach by a care manager in a
collaborative care model, have significantly better outcomes than usual care [51,108-110]. (See
'Collaborative care' below.)
Antidepressants are efficacious for late-life depression, based upon meta-analyses of randomized
trials [111,112]. As an example, a patient-level data meta-analysis of seven randomized trials (n =
2283 patients) compared antidepressants (bupropion, citalopram, duloxetine, escitalopram,
fluoxetine, or paroxetine) with placebo, and found that response (reduction of baseline symptoms
≥50 percent) occurred in more patients who received active treatment than placebo (49 versus 40
percent) [113]. Duration of illness (current age minus age at onset of depression) was associated
with response, such that response was greater in patients with a duration of illness >10 years,
compared with patients with a duration of illness <2 years.
Although antidepressants are efficacious for late-life major depression, efficacy may be less robust
in older patients than younger patients:
● A meta-analysis of 15 randomized trials compared antidepressants with placebo in 4756

patients aged 55 years and older (mean age 70 years). Response was greater with
antidepressants (relative risk 1.3, 95% CI 1.2-1.5) [111]. However, in the subgroup of patients
with a minimum age of 65 or 75 years (mean age 74 years; six trials, 1840 patients),
response was comparable for antidepressants and placebo. Both analyses were limited by
heterogeneity across pooled trials, the lack of trials that focused upon patients older than 80
years, and the exclusion of more severely depressed patients.
● A meta-analysis of patient level data from four randomized trials compared fluoxetine (10 to
30 mg per day) with placebo in 960 geriatric patients (older than 60 years) who were treated
for six weeks [114]. Although rating scale scores improved more with fluoxetine than placebo,
both response and remission were comparable for the two groups. In addition, a separate
analysis of adults (12 trials, 2635 patients) found that the improvement of rating scale scores
for adults was nearly double that for geriatric patients.
● A subsequent randomized trial compared duloxetine with placebo in 299 patients aged 65
years or more [115]. For both groups, remission was comparable (approximately 50 percent).
Exercise may be effective in the treatment of minor or major depression in the elderly [116].
Patients with major depression, however, may be difficult to engage in an exercise program and
would likely benefit from concomitant pharmacotherapy or psychotherapy. Exercise is discussed
elsewhere in this topic. (See 'Exercise' below.)
Psychotherapy — Psychotherapy is a useful but frequently underutilized treatment for elderly

depressed patients [106,117]. The availability of adequately trained therapists is a limiting factor,
and health insurance coverage for psychotherapy is often incomplete. Available formats include
individual, couples, family, or group therapy. Settings include private offices, community senior
centers, partial hospital day programs or intensive outpatient group programs. The discussion
below focuses upon the efficacy of psychotherapy in older adults; a general discussion of
psychotherapy is presented separately. (See "Overview of psychotherapies".)
Multiple randomized trials have found that psychotherapy is beneficial for late-life depression. As
an example, a meta-analysis of 27 trials (n >2000 patients) compared various psychotherapies
with different controls and found a significant, clinically moderate to large effect favoring
psychotherapy [118]. However, heterogeneity across studies was substantial and publication bias
was significant.
Short-term treatments include cognitive-behavioral therapy (CBT), interpersonal psychotherapy,

and problem-solving therapy, which are delivered over a period of two to four months and are
effective for older patients [119-123]. CBT is the most widely studied psychotherapy. A meta-
analysis of 10 randomized trials (380 elderly depressed patients) found a significant, clinically
large effect favoring CBT over treatment as usual or waiting list controls; heterogeneity across
studies was small to moderate [124]. A prior meta-analysis of three trials found that improvement
of depression was comparable for CBT and interpersonal psychotherapy [123]. Additional
information about the efficacy of interpersonal psychotherapy for elderly depressed patients is
discussed separately (see "Interpersonal Psychotherapy (IPT) for depressed adults: Indications,
theoretical foundation, general concepts, and efficacy", section on 'Older patients').
Multiple randomized trials have found problem-solving therapy can be beneficial [108]:
● A 12-week trial compared problem-solving therapy with supportive therapy in 221 non-
demented patients with major depression and executive dysfunction (difficulty with goal
setting and planning, and with initiating and sequencing behavior) [125,126]. Executive
dysfunction is associated with poor response to antidepressants. Remission of depression
occurred in more patients who received problem-solving therapy compared with controls (46
versus 28 percent). In addition, improvement of disability (self-care, communicating, and
psychosocial functioning) was greater with problem-solving therapy, and the advantage was
retained at the 24-week follow-up after the end of treatment.
● Another 12-week trial compared problem-solving therapy with supportive therapy in 74

patients with major depression and cognitive impairment ranging from mild deficits to
moderate dementia [127]. Both interventions were administered weekly in the home.
Remission of depression was greater with problem-solving therapy than supportive therapy
(38 versus 14 percent). In addition, reduction of disability was greater with problem-solving
therapy.
Life review therapy can help older patients with depression. A three-month randomized trial
compared life review therapy (eight group therapy sessions, two hours each) with usual care in
202 patients with mild to moderate depressive syndromes. Improvement of depression as well as
anxiety was greater with active treatment [128].
Psychotherapy and community-based programs for older adults may be particularly helpful for
patients with minor depression, for whom pharmacologic intervention has not demonstrated
consistent effectiveness [74,124].
Treatment for anxiety — One randomized trial of elder patients with generalized anxiety
disorder found that cognitive behavioral therapy (CBT) delivered in the primary care setting by
clinicians with expertise in CBT, compared with enhanced usual care (biweekly telephone contact),
decreased worry symptoms and moderately improved depressive symptoms in these patients
[129]. Whether CBT is effective for anxiety in association with major depression has not been
studied in randomized trials.
Medication acceptance by patients — Many older patients are reluctant to take medication for
their depression. Interviews with patients 60 years and older with depression (N = 68) found the
following concerns expressed: fear of medication dependence, rejection of concept of depression
as a medical illness, belief that medications would inhibit normal emotional reactions, and prior
negative experience with medications for depression [130]. Understanding why a patient may be
reluctant to initiate medication can promote clinician-patient dialogue to address their specific
concerns and initiate effective treatment.
Medication selection and management — A systematic review of 26 randomized trials that

compared antidepressants from different classes in head-to-head trials in patients aged 55 and
older found little difference in efficacy between medication classes [131]. However, there was a
higher withdrawal rate due to side effects for patients treated with tricyclic antidepressants,
compared with selective serotonin reuptake inhibitors (SSRIs). These findings suggest that side
effect profiles should be a major determinant in medication selection [132,133].
Medications typically take up to four to six weeks to show efficacy. In elderly patients a full
antidepressant response may not occur until 8 to 12 or even 16 weeks of therapy [132,134,135].
However, one study of 472 older patients with major depression found that patients who had no
improvement at all by 4 weeks of treatment were unlikely to respond even after 8 additional
weeks, and would be candidates for an early change in their treatment plan [136].
Monotherapy is preferred in the elderly in order to minimize drug side effects and drug-drug
interactions. Although one non-randomized open label study demonstrated good response to
augmentation for treatment-resistant older patients with no medical contraindication to
augmentation medications (lithium, bupropion, or nortriptyline) [137], combination strategies for
augmented or accelerated responses in the elderly are preferably avoided in the primary care
setting.
Initial medication dosage should be adjusted for the older adult, typically cutting the usual starting
dose for younger patients in half. Lower starting doses will compensate for decreased drug
clearance in the elderly, minimize initial side effects, and promote medication compliance and
maintenance. However, under-treatment of elderly depressed patients is well documented; it is
important to reach the same therapeutic dosage range as in younger adults in order to maximize
the chances of achieving complete remission.
Patients should be contacted or seen within two weeks of initiating medication to discuss
tolerance, address concerns, and adjust dose as indicated. Patients should have an office visit
within two to four weeks of initiation of medication treatment to assess for response,
complications, or deterioration. Depression-specific case management, (involving specially trained
nurses or social workers collaborating with primary care physicians to assist with depression
identification, guideline-based treatment and follow-up) was effective, compared with usual care, in
reducing mortality and depressive symptoms in older patients with major depression in a
randomized trial involving 20 primary care practices in three United States cities [138]. (See
'Collaborative care' below.)
Duration of treatment — The usual course of treatment for the first lifetime episode of unipolar
major depression in adults is 6 to 12 months beyond the time of achieving full remission. The goal
of continuation and maintenance treatment is to prevent relapse. Relapse rates in the elderly are
higher than in younger populations, which may indicate a need for longer periods of maintenance
therapy [139]. Prior to discontinuing maintenance treatment, clinicians should educate patients
about monitoring themselves for symptoms of recurrent episodes, and restarting treatment if
symptoms recur.
Evidence for the efficacy of maintenance treatment includes a meta-analysis of six randomized
trials that compared antidepressants (citalopram, dothiepin, escitalopram, nortriptyline, or
sertraline) with placebo for up to three years in 708 elderly patients who remitted from unipolar
major depressive episodes [140]. Recurrent episodes occurred in fewer patients who received
antidepressants than placebo (37 versus 59 percent). In addition, discontinuation of treatment due
to side effects was comparable.
Maintenance treatment with monthly psychotherapy, either alone or as add-on treatment with
pharmacotherapy, does not appear to be effective for preventing recurrent late life depressive
episodes. As an example, a two year randomized maintenance trial found that interpersonal
psychotherapy did not prevent recurrence [141]. Among patients 70 years of age and older who
had responded to treatment for unipolar major depression (N = 116) and were then assigned to
one of four maintenance treatments, the rate of recurrence was as follows:
● Paroxetine (10 to 40 mg per day) plus monthly interpersonal psychotherapy – 35 percent

● Paroxetine plus monthly "sham" psychotherapy (clinical management sessions) – 37 percent
● Pill placebo plus psychotherapy – 68 percent
● Placebo plus clinical management – 58 percent
For older patients who experience frequent relapses or recurrences, or who have dysthymic
disorder, long-term treatment may be needed; for patients requiring continuous treatment beyond
two to three years, consultation with a psychiatrist may be helpful. Studies in adult populations
younger than age 65 suggest that chronic antidepressant therapy should be considered for
patients with three or more serious episodes of depression before age 50. However, similar data
are lacking for treatment of recurrent depression in older populations and consultation with a
psychiatrist may be helpful in such cases, too.
Discontinuing antidepressants may be prompted by tachyphylaxis or side effects, or by the need to

initiate another medication that may cause a drug-drug interaction with the existing
antidepressant. Development of an intercurrent illness, especially of major organ, cerebral, or
systemic disease, may also make continuation of antidepressants problematic. Long term safety
data on chronic antidepressant use in the elderly with chronic comorbid medical conditions are
lacking.
Additional information about continuation and maintenance treatment is discussed separately.

(See "Unipolar depression in adults: Continuation and maintenance treatment".)
Antidepressant medications
Selective serotonin reuptake inhibitors (SSRIs) — SSRIs are considered first line for
treatment of depressive disorders in older adults due to better tolerability, ease of use, and general
safety, especially in overdose (table 6) [134].
Resolution of depressive symptoms, usually between four to six weeks, may take longer in the
elderly. Potential side effects of SSRIs of special concern in the elderly include Parkinsonism,
akathisia, anorexia, sinus bradycardia, and hyponatremia [142]. A dose-related increased risk for
fragility fractures (fractures resulting from minimal trauma) was reported in one observational
study [143]. Risk factors may include extensive medical or neurologic comorbidity or concurrent
use of multiple medications. Careful monitoring is advised in more frail populations.
One study did suggest an increased rate of suicide in men 66 years and older in the first month of
treatment with an SSRI, compared to other antidepressant drugs; this effect was not seen during
subsequent treatment [144]. Monitoring for suicide risk is recommended in early therapy with an
SSRI. Nonetheless, and as previously noted, treating depression can reduce suicidal ideation (see
'Suicide risk' above) [51,145].
Despite greater acceptance and clinical recommendations, SSRIs are probably not more
efficacious than older antidepressants. Comparison studies in the elderly show that the difference
in clinical efficacy is small, the range of placebo response is broad, and that a significant number
of elderly retain significant residual depressive symptomatology [133-135]. For severe forms of
melancholic and psychotic depression, SSRI agents may be less efficacious than other drugs or
electroconvulsive therapy (ECT) [133,146].
The United States Food and Drug Administration issued warnings that citalopram causes dose-
dependent QT interval prolongation that can lead to arrhythmias, and thus recommends that the
maximum dose in patients >60 years of age should not exceed 20 mg per day [147,148].
Additional information about the citalopram warnings and cardiac effects of SSRIs is discussed
separately, as are the pharmacology, administration, and other side effects of SSRIs. (See
"Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects".)
Serotonin-norepinephrine reuptake inhibitors (SNRIs) — Serotonin-norepinephrine

reuptake inhibitors (SNRIs), which include venlafaxine and duloxetine, are currently used as
second-line agents for treatment failure with SSRIs (table 6).
These agents may also be useful in patients with comorbid pain. In a nine-week randomized study
comparing duloxetine and placebo for treatment of major depression in patients over age 55, the
duloxetine group had a greater treatment response for depression as well as reduction in overall
pain, back pain, and pain while awake [149]. However, discontinuation due to adverse events was
significantly greater in the duloxetine group (21 percent compared to 7 percent).
Few comparison studies exist between SSRIs and SNRIs in the elderly. Frail nursing home
patients showed a poorer tolerance to venlafaxine when compared to sertraline in one study [150].
The SNRIs are considered safe for use in most elderly populations, although both carry a dose-
dependent risk for diastolic hypertension. In a study of older adults, venlafaxine extended-release
(XR) was found to cause less GI distress and agitation than the immediate release preparation
[151].
The SNRIs, as well as SSRIs, have resulted in the serotonin syndrome, but more data are needed
to identify risk factors for elderly patients [152]. Serotonin syndrome manifests as altered mental
status, myoclonus, tremors, hyperreflexia, fever, and autonomic changes among other findings
[153,154]. (See "Serotonin syndrome (serotonin toxicity)".)
The pharmacology, side effects, and general administration of SNRIs are discussed separately.
(See "Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and
side effects".)
Atypical antidepressants — Atypical antidepressants include agomelatine, bupropion, and

mirtazapine (table 6). Few studies exist in populations of elderly [155].
Bupropion is generally considered an activating agent, so it may be useful in patients who

complain of lethargy, daytime sedation, or fatigue. Bupropion is contraindicated in patients with
seizure disorders, concurrent use of benzodiazepines or other CNS depressants, alcohol
detoxification, or prior or current diagnosis of bulimia nervosa. Dose-dependent diastolic
hypertension is a concern in the older patient.
Mirtazapine is also used as a second line agent. Mirtazapine appears to be useful for elderly
patients with insomnia, agitation or restlessness, and anorexia or weight loss. It may also be
useful in patients with Parkinsonism, essential tremor, or nausea from chemotherapy, and is
available as a rapidly dissolving sol-tab preparation [156].
Common side effects of mirtazapine include sedation, especially at initiation and at lower dosages,
appetite increase and weight gain, dry mouth, and constipation. The sedating effects of
mirtazapine tend to diminish with acclimation and also tend to be less pronounced at higher
dosages where the noradrenergic effects predominate over the antihistaminergic effects.
Agomelatine was approved for use in Europe in 2009 but is not approved in the United States. A
review identified only one controlled trial (unpublished) in the elderly, in which 218 patients 60
years and older with major depression, were randomly assigned to agomelatine 25 mg per day or
placebo for six weeks [157]. There was no significant difference in Montgomery Asberg
Depression Rating Scale scores. In addition, the rate of response, defined by at least a 50 percent
decrease in scores, did not differ significantly between agomelatine and placebo (46 versus 52
percent).
The pharmacology, side effects, and general administration of atypical antidepressants are
discussed separately. (See "Atypical antidepressants: Pharmacology, administration, and side
effects".)
Serotonin modulators — Serotonin modulators include nefazodone, trazodone, and

vilazodone.
Nefazodone is available in the United States in a generic preparation only, as the brand (Serzone)
was voluntarily removed from the market due to hepatotoxicity concerns. Nefazodone has been
withdrawn from several countries outside the United States, including European countries and
Canada. Common side effects include sedation and restlessness. It appears to have relatively
good GI tolerance. Nefazodone may be useful in depressed patients who complain of insomnia,
anxiety, or agitation. Nefazodone is a potent inhibitor of the CYP450-3A4 isoenzyme, so significant
drug-drug interactions may occur with commonly used macrolide antibiotics, cardiac
antiarrhythmics, and other psychotropic agents.
Trazodone is rarely used solely as an antidepressant but is still commonly used as a soporific and
mild sedative, especially at lower doses. Antidepressant effects tend to be seen only at higher
dosages, where concerns about orthostatic hypotension and excessive daytime sedation limit its
use. Both nefazodone and trazodone have been associated with hyponatremia and trazodone has
been associated with the rare but potentially serious side effect of priapism [153].
The pharmacology, side effects, and general administration of serotonin modulators are discussed
separately. (See "Serotonin modulators: Pharmacology, administration, and side effects".)
Tricyclic and tetracyclic antidepressants — While no longer considered first or second-line

agents for the treatment of depression in any age group, these agents may be useful for treatment
failure with other antidepressants (table 6). A few studies suggest that cyclic antidepressants may
have superior efficacy in the elderly with melancholic or delusional depression, and these
antidepressants are the only class shown to reduce the risk of relapse after a course of
electroconvulsive therapy (ECT) [135,146,158].
Cyclic antidepressants must be used cautiously in patients with cardiac conduction abnormalities,
arrhythmias, narrow angle glaucoma, urinary retention, or BPH, and patients should be followed
for development or worsening of orthostatic hypotension and constipation. Additionally, patients
with Alzheimer-type dementia may experience worsening confusion. Tricyclic and tetracyclic
antidepressants are discussed separately. (See "Tricyclic and tetracyclic drugs: Pharmacology,
administration, and side effects".)
Monoamine oxidase inhibitors (MAOIs) — This class of antidepressants is rarely used

except when previously initiated and tolerated, or in the patient who is treatment resistant to all
other antidepressants (table 7). MAOIs do have proven benefit, with some studies suggesting
superior efficacy in atypical (reverse neurovegetative) depression, mixed anxiety-depressive
states, and panic disorder, although limited research studies are found in elderly populations [159].
Patients treated with MAOIs require special dietary and medication restrictions to prevent the
serotonin syndrome and hyperadrenergic crisis. Because of potential severe side effects, these
medications are best prescribed by a psychiatrist or physician with extensive experience in use of
these medications. Aside from these concerns, these medications are surprisingly well tolerated in
the elderly. Common side effects include orthostatic hypotension, activation, and insomnia. In
contrast to TCAs, these medications are relatively devoid of cardiac conduction effects.
The pharmacology, side effects, and general administration of monoamine oxidase inhibitors are
discussed separately. (See "Monoamine oxidase inhibitors (MAOIs) for treating depressed
adults".)
Adjunctive medications
Methylphenidate — For patients with late-life major depression, simultaneously prescribing an

antidepressant with methylphenidate at the onset of treatment may improve outcomes. A 16-week
randomized trial enrolled patients (n = 143; mean age 70 years) with unipolar major depression
who were free of psychotropic medications for at least two weeks, and assigned them to receive
citalopram plus methylphenidate, citalopram plus placebo, or methylphenidate plus placebo [160].
Electrocardiograms were performed at baseline, and patients with atrial or ventricular arrhythmias
or acute ischemic features were excluded. Citalopram doses ranged from 20 to 60 mg/day and
methylphenidate from 5 to 40 mg/day. Improvement was greater and occurred more quickly with
combination treatment than either citalopram monotherapy or methylphenidate monotherapy. In
addition, discontinuation of treatment due to side effects appeared to be comparable for the three
groups. It is worth noting that stimulants can lead to adverse cardiac effects, and that the
maximum dose of citalopram recommended by the United States Food and Drug Administration
for patients aged >60 years is 20 mg/day. (See "Selective serotonin reuptake inhibitors:
Pharmacology, administration, and side effects", section on 'Citalopram'.)
Aripiprazole — For patients with treatment-resistant late-life depression, adjunctive

aripiprazole can be efficacious. A 12-week randomized trial compared add-on aripiprazole with
placebo in patients (n = 181) who did not initially remit with open label venlafaxine [161].
Aripiprazole was started at 2 mg per day and titrated up as needed and tolerated to a target dose
of 10 mg per day (range 2 to 15 mg per day; median final daily dose 7 mg). Remission occurred in
more patients who received aripiprazole than placebo (44 versus 29 percent). However,
aripiprazole caused more akathisia (26 versus 12 percent of patients) and Parkinsonism (17
versus 2 percent). Weight gain was also greater with active drug than placebo (1.9 versus 0.0 kg).
Information about adjunctive second-generation antipsychotics for the general population of

patients with treatment-resistant depression is discussed separately. (See "Unipolar depression in
adults: Treatment with second-generation antipsychotics".)
Other — Other add-on medications that can be used with antidepressants in treatment-
resistant late-life depression include lithium and triiodothyronine. (See "Unipolar depression in
adults: Treatment with lithium" and "Unipolar depression in adults: Augmentation of
antidepressants with thyroid hormone".)
Quetiapine — Although monotherapy with the second-generation antipsychotic quetiapine may

be effective for major depression, the risk of short- and long-term side effects is such that
quetiapine is not a first or second line treatment. Evidence for the efficacy of quetiapine includes a
nine-week randomized trial that compared quetiapine extended release monotherapy (50 to 300
mg per day, median dose 159 mg per day) with placebo in 335 patients with late-life,
nonpsychotic, unipolar major depression [162]. Remission occurred in more patients who received
quetiapine than placebo (45 versus 17 percent). Discontinuation of treatment following an adverse
event occurred in more than twice as many patients who received quetiapine (10 versus 4
percent). Common side effects of quetiapine included sedation, dry mouth, and extrapyramidal
symptoms. Although these findings indicate that quetiapine extended release may have some
utility for major depression, ongoing concerns remain about safety issues and side effects,
especially with long term treatment. The use of second-generation antipsychotics as adjunctive
treatment for unipolar major depression that does not respond to antidepressant monotherapy is
discussed separately. (See "Unipolar depression in adults: Treatment with second-generation
antipsychotics".)
Neurostimulation — Several brain stimulation procedures for treating major depression are
clinically available or under investigation. An overview of these procedures is discussed separately
(see "Depression in adults: Overview of neuromodulation procedures").
Electroconvulsive therapy (ECT) — ECT remains an important and viable treatment option in
the elderly. ECT is used for depressed patients who have not responded to adequate
antidepressant trials, and patients with severe major depression that is life-threatening or
significantly impairs functioning [83,163-166]. Indications for use, description of the procedure,
morbidity, and risk assessment for ECT are discussed separately. (See "Overview of
electroconvulsive therapy (ECT) for adults" and "Unipolar major depression in adults: Indications
for and efficacy of electroconvulsive therapy (ECT)", section on 'Older age' and "Technique for
performing electroconvulsive therapy (ECT) in adults" and "Medical consultation for
electroconvulsive therapy".)
Other brain stimulation therapies — Other brain stimulation therapies have been evaluated
for treatment of medication resistant depression; these therapies include repetitive transcranial
magnetic stimulation (rTMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS).
However, there are no randomized trials that have demonstrated any benefit of these modalities in
the elderly. Neuromodulation is discussed in more detail separately. (See "Depression in adults:
Overview of neuromodulation procedures" and "Unipolar depression in adults: Indications,
efficacy, and safety of transcranial magnetic stimulation (TMS)", section on 'Elderly' and "Unipolar
depression in adults: Treatment with surgical approaches".)
Exercise — Systematic reviews of controlled trials indicate that physical exercise is beneficial for
depressed patients 60 years and older [116,167,168]. As an example, a meta-analysis of seven
randomized trials (n = 519 patients) compared exercise with a non-exercise control condition;
exercise typically consisted of three to five sessions (each lasting 30 to 45 minutes) per week, for
three to four months [169]. The analysis found a significant, but clinically small effect favoring
exercise.
Physical exercise may be a first-line treatment for patients with mild or moderate depression, but it
may be difficult for them to engage in exercise. Thus, additional treatment with medications or
psychotherapy may be needed.
The two main types of exercise are cardiovascular (aerobic) activities such as walking, running, or
swimming, and resistance training (nonaerobic) that involves lifting weights. Both types of exercise
can help reduce depressive symptoms, but the results appear to be more consistent for
cardiovascular exercise [167]. One review found that late-life depressive symptoms were
substantially reduced in more patients who participated in short-term (eg 12-week), supervised,
group-based, cardiovascular exercise programs, compared with patients in control groups (45 to
65 versus 25 to 30 percent) [5].
The benefits of exercise appear to persist in depressed, older patients who continue to exercise
for the long term. A study randomly assigned 438 adults with osteoarthritis, 60 years or older, to
cardiovascular exercise, resistance exercise, or health education classes (to control for the
therapeutic effects of socialization) [170]. The exercise programs were conducted under
supervision for three months in a facility, and then for 15 months at home with face-to-face or
telephone contact by the exercise leader. Among the 98 patients with major depression, the
reduction in depression rating scale scores at month 18 was significantly greater for those
assigned to cardiovascular exercise compared with health education (40 versus 20 percent
reduction). Resistance exercise did not differ significantly from health education.
Additional information about exercise and treatment of depression as well as exercise in older
adults (including assessment of individuals with cardiovascular contraindications to physical
activity), is discussed separately. (See "Physical activity and exercise in older adults".)
Bright light — Bright light therapy may be beneficial for depressed patients who do not have
seasonal affective disorder. A three-week randomized trial compared bright light treatment (pale
blue, approximately 7500 lux) with placebo (dim red, approximately 50 lux) in 89 elderly patients
with nonseasonal major depression. Response (improvement from baseline ≥50 percent) occurred
in more patients who received bright light (58 versus 34 percent), which was well-tolerated [171].
Collaborative care — Collaborative care programs emphasize patient education and use non-
physician mental health professionals or depression care managers to integrate psychiatric and
primary care; these programs (also called integrative care and care management) for elderly
depressed patients can improve outcomes [172,173]. As an example, the 12 month, multisite
Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) program compared
collaborative care with usual care in 1801 primary care patients with late life major depression
and/or persistent depressive disorder (dysthymia), and found that cost effectiveness and
improvement of symptoms (including suicidal ideation), physical functioning, and quality of life
were greater with collaborative care [52,108,110]. In addition, the benefits were sustained one
year after termination of the collaborative intervention [174]. Other trials have found comparable
results [51,175,176].
Collaborative care appears to improve general medical outcomes as well as depression. Patients
at one of the IMPACT study sites were followed for eight years, including 168 patients without
cardiovascular disease at baseline [177]. Cardiovascular events (fatal or nonfatal myocardial
infarction or stroke) occurred in fewer patients who received collaborative care than usual care (28
versus 47 percent).
In addition, collaborative care programs may decrease all-cause mortality in late-life depression. A
randomized trial compared collaborative care with usual care in 396 elderly primary care patients
with unipolar major depression as well as 203 patients with minor depression [178]. The study also
enrolled 627 patients without depression. Collaborative care involved depression care managers
(social workers, nurses, or psychologists) who were supervised by psychiatrists and worked with
primary care physicians to provide antidepressants and/or psychotherapy for depression; increase
antidepressant doses or switch antidepressants when indicated; and monitor symptoms, side
effects, and adherence to treatment. Patients were treated for up to 24 months and followed for a
median of 98 months, during which time 405 patients died. The primary findings were as follows:
● Among patients with major depression, the risk of death was 24 percent less with
collaborative care than usual care (hazard ratio 0.76, 95% CI 0.57-1.00).
● The risk of death for patients with major depression who received collaborative care and
patients who were not depressed was comparable (hazard ratio 1.1, 95% CI 0.8-1.4). By
contrast, mortality was greater (nearly twice as high) for patients with major depression in
usual care, compared with nondepressed patients (hazard ratio 1.9, 95% CI 1.6-2.3).
● For patients with minor depression, collaborative care did not affect the risk of mortality.
The elements of collaborative care are also helpful in psychiatric practices. A six-month
randomized trial compared care management plus pharmacotherapy with pharmacotherapy alone
in 57 elderly patients, who were treated for depressive disorders in a psychiatric clinic [179]. Care
management consisted of eight telephone calls from a psychologist, who educated patients about
depression, treatment options, and adherence; monitored symptoms and adverse events; and
reminded patients about their next visit to the clinic. Remission occurred in more patients who
received care management plus pharmacotherapy than pharmacotherapy alone (55 versus 29
percent).
Additional information about collaborative care in mixed age populations is discussed separately.
(See "Unipolar depression in adult primary care patients and general medical illness: Evidence for
the efficacy of initial treatments", section on 'Collaborative care'.)
Home based care — Home based interventions for mildly depressed, older patients with limited
mobility or access to care may be helpful. However, the availability of home based interventions is
limited.
Evidence supporting the efficacy of home based care includes the following [180]:
● A four-month randomized trial compared at-home care with a waiting list control condition in
208 older African Americans with depressive symptoms [181]. The active treatment was
administered by social workers and included referrals for medical and social services,
education about depression and stress reduction, and behavioral activation. Remission of
symptoms occurred in more patients in the intervention group than the waiting list group (44
versus 27 percent).
● A one year randomized trial compared home based treatment with usual care in 138 patients
with either minor depression or persistent depressive disorder (dysthymia) [121]. The home
based program was administered by social workers and included eight sessions of problem
solving therapy and behavioral activation, as well as recommendations to patients’ physicians
about use of antidepressants; usual care included a letter to patients’ physicians about the
depression diagnosis. Remission was greater in patients who received home based care than
usual care (36 versus 12 percent).
Family support — Family members should be involved in the care of patients with late-life major
depression, and be educated about the signs and symptoms, treatment, and prognosis of the
illness [172]. The family can provide information about symptoms that the patient may not reveal
and can encourage adherence to treatment. Family meetings for assessment and treatment of
patients with major depression are discussed separately. (See "Unipolar depression in adults:
Family and couples therapy".)
Other — Cognitive impairment in late-life depression raises the question as to whether

cholinesterase inhibitors are useful; however, a review of four randomized trials found that
cholinesterase inhibitors as adjunctive treatment with antidepressants provided no clear benefit
[182]. In the largest trial, donepezil was compared with placebo as add-on maintenance treatment
with an antidepressant in patients aged 65 years and older [183]. Cognitive functioning was
superior with donepezil at one year but not two years. However, donepezil appeared to increase
the risk of recurrence of major depression. In addition, cholinesterase inhibitors may provoke
symptoms (eg, dysphoria) that mimic depression. Thus, their use in this population requires close
monitoring.
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.”
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on “patient info” and the keyword(s) of interest.)
● Basics topics (see "Patient education: Coping with high drug prices (The Basics)")
● Beyond the Basics topics (see "Patient education: Coping with high drug prices (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
Epidemiology and diagnosis
● Late-life depression often goes undetected and has a significant adverse impact on quality of
life, outcomes of medical disease, healthcare utilization, and morbidity and mortality. The
overwhelming majority of older adults with depression initially present to primary care, often
with somatic complaints. (See 'Introduction' above.)
● Depression is not a normal consequence of aging. Healthy independent elders have a lower
prevalence rate of major depression than the general population. Rates increase greatly with
medical illness, particularly cancer, MI, and neurological disorders such as stroke and
Parkinson disease. (See 'Risk factors' above.)
● Suicide rates are almost twice as high in the elderly, with the rate highest for white men over
85 years of age. Most older adults who commit suicide had seen a clinician within the
previous month. (See 'Suicide risk' above.)
● Minor depression in late life is more prevalent than major depression, has significant health
consequences, and responds to treatment. (See 'Minor depression' above.)
● Delusional (psychotic) depression is a very severe illness and can be lethal. Cognitive deficits
may be pronounced and similar to dementia. However, both depressive symptoms and
cognitive impairment respond to treatment with antidepressants, distinguishing these patients
from those with Alzheimer disease and secondary depression. (See 'Psychotic depression'
above.)
● Depression associated with cerebrovascular disease is characterized by psychomotor

retardation, anhedonia, greater frontal executive dysfunction, and poor insight. (See 'Vascular
depression' above.)
● Depression in the elderly can be challenging to diagnose. Screening instruments are available
that can help identify patients who need further evaluation for depression. (See 'Screening
instruments' above.)
Treatment
● Psychotherapy is effective in older adults, although for moderate to severe depression in late
life, pharmacotherapy or a combination of pharmacotherapy and psychotherapy is
recommended. (See 'Psychotherapy' above.)
● Medication monotherapy is preferred in the elderly in order to minimize drug side effects and
drug-drug interactions. Initial medication dosage should be adjusted for the older adult,
typically halving the usual starting dose for younger patients but full therapeutic doses are
often required to achieve the desired responses. (See 'Medication selection and
management' above.)
● All medications typically take four to six weeks to show efficacy; in elderly patients a full
antidepressant response may not occur until 8 to 12 or even 16 weeks of therapy. Long-term
treatment may be necessary to prevent recurrence. (See 'Medication selection and
management' above and 'Duration of treatment' above.)
● Patients should be contacted or seen within two weeks of initiating medication to discuss
tolerance and adjust dose as indicated, and should have an office visit within two to four
weeks of treatment to assess response, monitor for side-effects, and address any
complications or deterioration. (See 'Medication selection and management' above.)
● SSRIs are first-line antidepressants because of safety and tolerability. However, in patients
aged 60 years and above, the maximum recommended dose of citalopram is 20 mg per day
due to concerns about dose-dependent QT interval prolongation that can lead to arrhythmias.
(See 'Selective serotonin reuptake inhibitors (SSRIs)' above and "Selective serotonin
reuptake inhibitors: Pharmacology, administration, and side effects".)
● Mirtazapine may be useful for patients with insomnia, agitation, restlessness, or anorexia and
weight loss. Venlafaxine and duloxetine are frequently used as second line agents and may
be particularly helpful in patients with depression and neuropathic pain. (See 'Serotonin-
norepinephrine reuptake inhibitors (SNRIs)' above.)
● Tricyclic antidepressants are third- or fourth-line therapy in the elderly due to significant
arrhythmic side effects, as well as anticholinergic effects causing urinary retention,
orthostasis, and possible exacerbation of dementia. These drugs, when necessary, are
probably best managed by a psychiatrist or physician with special expertise and experience in
managing these medications in the elderly. (See 'Tricyclic and tetracyclic antidepressants'
above.)
● MAO inhibitors can be used for depression that is resistant to other agents. This class of
drugs has not been well studied in the elderly. They should also be prescribed by a
psychiatrist or physician with special expertise and experience with these medications,
because of their serious side effect profile. (See 'Monoamine oxidase inhibitors (MAOIs)'
above.)
● There is evidence that for elderly primary care patients with major depression, improvement
of symptoms (including suicidal ideation), physical functioning, and quality of life is greater,
and that mortality is lower, with collaborative care than with usual care. (See 'Collaborative
care' above.)
● ECT is used more frequently in the elderly than in younger patients, and may be effective for
the older patient who is intolerant of medications or not responding to adequate medication
trials. ECT is generally well tolerated in the older patient, although it causes transient memory
loss. (See "Unipolar major depression in adults: Indications for and efficacy of
electroconvulsive therapy (ECT)", section on 'Older age'.)
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162. Katila H, Mezhebovsky I, Mulroy A, et al. Randomized, double-blind study of the efficacy and
tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly
patients with major depressive disorder. Am J Geriatr Psychiatry 2013; 21:769.
163. Brodaty H, Hickie I, Mason C, Prenter L. A prospective follow-up study of ECT outcome in
older depressed patients. J Affect Disord 2000; 60:101.
164. Tew JD Jr, Mulsant BH, Haskett RF, et al. Acute efficacy of ECT in the treatment of major
depression in the old-old. Am J Psychiatry 1999; 156:1865.
165. Husain MM, Rush AJ, Fink M, et al. Speed of response and remission in major depressive
disorder with acute electroconvulsive therapy (ECT): a Consortium for Research in ECT
(CORE) report. J Clin Psychiatry 2004; 65:485.
166. O'Connor MK, Knapp R, Husain M, et al. The influence of age on the response of major
depression to electroconvulsive therapy: a C.O.R.E. Report. Am J Geriatr Psychiatry 2001;
9:382.
167. Frazer, CJ, Christensen, H, Griffiths, KM. Effectiveness of treatments for depression in older
people, Med J Aust 2005; 182:627.
168. Blake H, Mo P, Malik S, Thomas S. How effective are physical activity interventions for
alleviating depressive symptoms in older people? A systematic review. Clin Rehabil 2009;
23:873.
169. Bridle C, Spanjers K, Patel S, et al. Effect of exercise on depression severity in older people:
systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry 2012;
201:180.
170. Penninx BW, Rejeski WJ, Pandya J, et al. Exercise and depressive symptoms: a comparison
of aerobic and resistance exercise effects on emotional and physical function in older
persons with high and low depressive symptomatology. J Gerontol B Psychol Sci Soc Sci
2002; 57:124.
171. Lieverse R, Van Someren EJ, Nielen MM, et al. Bright light treatment in elderly patients with
nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen
172. Unützer J, Park M. Older adults with severe, treatment-resistant depression. JAMA 2012;
308:909.
173. Chen S, Conwell Y, He J, et al. Depression care management for adults older than 60 years
in primary care clinics in urban China: a cluster-randomised trial. Lancet Psychiatry 2015;
2:332.
174. Hunkeler EM, Katon W, Tang L, et al. Long term outcomes from the IMPACT randomised
trial for depressed elderly patients in primary care. BMJ 2006; 332:259.
175. Alexopoulos GS, Katz IR, Bruce ML, et al. Remission in depressed geriatric primary care
patients: a report from the PROSPECT study. Am J Psychiatry 2005; 162:718.
176. Alexopoulos GS, Reynolds CF 3rd, Bruce ML, et al. Reducing suicidal ideation and
depression in older primary care patients: 24-month outcomes of the PROSPECT study. Am
J Psychiatry 2009; 166:882.
177. Stewart JC, Perkins AJ, Callahan CM. Effect of collaborative care for depression on risk of
cardiovascular events: data from the IMPACT randomized controlled trial. Psychosom Med
2014; 76:29.
178. Gallo JJ, Morales KH, Bogner HR, et al. Long term effect of depression care management
on mortality in older adults: follow-up of cluster randomized clinical trial in primary care. BMJ
2013; 346:f2570.
179. Jeong H, Yim HW, Jo SJ, et al. The effects of care management on depression treatment in
a psychiatric clinic: a randomized controlled trial. Int J Geriatr Psychiatry 2013; 28:1023.
180. Reifler BV, Bruce ML. Home-based mental health services for older adults: a review of ten
model programs. Am J Geriatr Psychiatry 2014; 22:241.
181. Gitlin LN, Harris LF, McCoy MC, et al. A home-based intervention to reduce depressive
symptoms and improve quality of life in older African Americans: a randomized trial. Ann
Intern Med 2013; 159:243.
182. McDermott CL, Gray SL. Cholinesterase inhibitor adjunctive therapy for cognitive impairment
and depressive symptoms in older adults with depression. Ann Pharmacother 2012; 46:599.
183. Reynolds CF 3rd, Butters MA, Lopez O, et al. Maintenance treatment of depression in old
age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of
donepezil combined with antidepressant pharmacotherapy. Arch Gen Psychiatry 2011;
68:51.
Topic 1719 Version 49.0
GRAPHICS
Prevalence of depressive disorders in various patient populations
* Prevalence range varies according to study.
Data from Birrer, RB, Vemuri, SP. Depression in later life: a diagnostic and therapeutic challenge. Am
Fam Physician 2004; 69:2375
Graphic 71214 Version 1.0
DSM-5 diagnostic criteria for a major depressive episode
A. Five (or more) of the following symptoms have been present during the same two-week period and represent a
change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest
or pleasure.
NOTE: Do not include symptoms that are clearly attributable to another medical condition.
1) Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg, feels sad,
empty, hopeless) or observations made by others (eg, appears tearful). (NOTE: In children and adolescents, can
be irritable mood.)
2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as
indicated by either subjective account or observation)
3) Significant weight loss when not dieting or weight gain (eg, a change of more than 5% of body weight in a
month), or decrease or increase in appetite nearly every day. (NOTE: In children, consider failure to make
expected weight gain.)
4) Insomnia or hypersomnia nearly every day
5) Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of
restlessness or being slowed down)
6) Fatigue or loss of energy nearly every day
7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not
merely self-reproach or guilt about being sick)
8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by their subjective
account or as observed by others)
9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a
suicide attempt or a specific plan for committing suicide
B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas
of functioning.
C. The episode is not attributable to the direct physiological effects of a substance or to another medical condition.
NOTE: Criteria A through C represent a major depressive episode.
NOTE: Responses to a significant loss (eg, bereavement, financial ruin, losses from a natural disaster, a serious
medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor
appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms
may be understandable or considered appropriate to the loss, the presence of a major depressive episode in
addition to the normal response to a significant loss should also be carefully considered. This decision inevitably
requires the exercise of clinical judgement based on the individual's history and the cultural norms for the
expression of distress in the context of loss.
D. The occurence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia,
schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other
psychotic disorders.
E. There has never been a manic or hypomanic episode.
NOTE: This exclusion does not apply if all of the manic-like or hypomanic-like epsidoes are substance-induced or
are attributable to the physiological effects of another medical condition.
Specify:
With anxious distress
With mixed features
With melancholic features
With atypical features
With psychotic features
With catatonia
With peripartum onset
With seasonal pattern
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright ©
2013). American Psychiatric Association. All Rights Reserved.
DSM-5 diagnostic criteria for persistent depressive disorder (dysthymia)
A. Depressed mood for most of the day, for more days than not, as indicated either by subjective account or
observation by others, for at least two years.
NOTE: In children and adolescents, mood can be irritable and duration must be at least one year.
B. Presence, while depressed, of two (or more) of the following:
1) Poor appetite or overeating.
2) Insomnia or hypersomnia.
3) Low energy or fatigue.
4) Low self-esteem.
5) Poor concentration or difficulty making decisions.
6) Feelings of hopelessness.
C. During the two-year period (one year for children or adolescents) of the disturbance, the individual has never
been without the symptoms in Criteria A and B for more than two months at a time.
D. Criteria for a major depressive disorder may be continuously present for two years.
E. There has never been a manic episode or a hypomanic episode, and criteria have never been met for cyclothymic
disorder.
F. The disturbance is not better explained by a persistent schizoaffective disorder, schizophrenia, delusional
disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.
G. The symptoms are not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication)
or another medical condition (eg, hypothyroidism).
H. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas
of functioning.
NOTE: Because the criteria for a major depressive episode include four symptoms that are absent from the
symptom list for persistent depressive disorder (dysthymia), a very limited number of individuals will have
depressive symptoms that have persisted longer than two years but will not meet criteria for persistent depressive
disorder. If full criteria for a major depressive episode have been met at some point during the current episode of
illness, they should be given a diagnosis of major depressive disorder. Otherwise, a diagnosis of other specified
depressive disorder or unspecified depressive disorder is warranted.
Specify if:
With anxious distress
With mixed features
With melancholic features
With atypical features
With mood-congruent psychotic features
With mood-incongruent psychotic features
With peripartum onset
Specify if:
In partial remission
In full remission
Specify if:
Early onset: If onset is before 21 years.
Late onset: If onset is at age 21 years or older.
Specify if (for most recent two years of persistant depressive disorder):
With pure dysthymic syndrome: Full criteria for a major depressive episode have not been met in at least the
preceding two years.
With persistent major depressive episode: Full criteria for a major depressive episode have been met
throughout the preceding two-year period.
With intermittent major depressive episodes, with current episode: Full criteria for a major depressive
episode are currently met, but there have been periods of at least eight weeks in at least the preceding two
years with symptoms below the threshold for a full major depressive episode.
With intermittent major depressive episodes, without current episode: Full criteria for a major depressive
episode are not currently met, but there has been one or more major depressive episodes in at least the
preceding two years.
Specify current severity:
Mild
Moderate
Severe
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright ©
2013). American Psychiatric Association. All Rights Reserved.
Depression in Alzheimer-type dementia
A. Three or more of the following symptoms, present during the same two-week period, and representing a change
from a previous level of functioning. Either item one or item two must be included:
1. Clinically significant depressed mood
2. Decreased positive affect or pleasure in response to social contacts and usual activities
3. Social isolation or withdrawal
4. Disturbed appetite
5. Disturbed sleep
6. Psychomotor retardation or agitation
7. Irritability
8. Fatigue or loss of energy
9. Feelings of worthlessness, hopelessness, or inappropriate guilt
10. Recurrent thoughts of death or suicidal ideation, plan, or any attempt
B. Meets criteria for Alzheimer-type dementia
C. Depressive symptoms cause clinically significant distress or disruption in function
D. Symptoms do not occur exclusively during an episode of delirium
E. Symptoms are not due to a direct physiologic effect from a substance (medication or drug of abuse)
F. Symptoms are not better accounted for by another condition

Specify if:
Co-occurring onset: onset antedates or co-occurs with AD symptoms
Post-AD onset: onset occurs after AD diagnosis
Specify if:
With psychosis of AD
With other significant behavioral signs or symptoms
With past history of mood disorder
AD: Alzheimer disease.
Screening instruments for late-life depression for use in primary care
Sensitivity Specificity Physically Cognitively

Inpatient Outpatient
percent percent ill impaired
Two-question 97 67 Unknown Yes Unknown No

screen
Geriatric 94 81 Yes Yes Yes Unknown

Depression
Scale (5-item)
Patient Health 88 88 Unknown Yes Yes Unknown

Questionnaire-
9 (9-item)
Cornell Scale 90 75 Yes Yes Unknown Yes

for Depression
in Dementia
(19-item)
Center for 93 73 No Yes Unknown No

Epidemiologic
Studies -
Depression
Scale (20-
item)
PHQ-9 depression questionnaire
Name: Date:
Over the last 2 weeks, how often have you been bothered Not at Several More Nearly
by any of the following problems? all days than every
half the day
days
Little interest or pleasure in doing things 0 1 2 3
Feeling down, depressed, or hopeless 0 1 2 3
Trouble falling or staying asleep, or sleeping too much 0 1 2 3
Feeling tired or having little energy 0 1 2 3
Poor appetite or overeating 0 1 2 3
Feeling bad about yourself, or that you are a failure, or that you 0 1 2 3
have let yourself or your family down
Trouble concentrating on things, such as reading the newspaper 0 1 2 3

or watching television
Moving or speaking so slowly that other people could have 0 1 2 3

noticed? Or the opposite, being so fidgety or restless that you
have been moving around a lot more than usual.
Thoughts that you would be better off dead, or of hurting 0 1 2 3

yourself in some way
Total ___ = ___ + ___ + ___ + ___
PHQ-9 score ≥10: Likely major depression
Depression score ranges:
5 to 9: mild
10 to 14: moderate
15 to 19: moderately severe
≥20: severe
If you checked off any problems, how difficult have these Not Somewhat Very Extremely
problems made it for you to do your work, take care of difficult difficult difficult difficult
things at home, or get along with other people? at all ___ ___ ___
___
PHQ: Patient Health Questionnaire.
Developed by Drs. Robert L Spitzer, Janet BW Williams, Kurt Kroenke, and colleagues, with an educational grant from
Pfizer, Inc. No permission required to reproduce, translate, display or distribute.
Drug properties and doses of antidepressants in older adults and medically ill
Starting Suggested Potential

Drug Precautions*
dose dose range advantages
Selective serotonin reuptake inhibitors (SSRIs) ¶
Escitalopram 5 mg every 5 to 20 mg daily Mild discontinuation symptoms Applies to escitalopram

morning or may occur absent tapering. and citalopram:
every Generally well tolerated.
evening Non-sedating, low risk of
sleep disturbance,
Citalopram 10 mg 10 to 20 mg Δ daily Dose-related risk of QT comparatively few
every prolongation ¶ Δ. significant drug
morning or interactions.
Mild discontinuation symptoms
every may occur absent tapering. Good choice for initial
evening treatment of depression
in most older adults.
Sertraline 12.5 to 25 25 to 200 mg daily More frequent gastrointestinal Non-sedating, low risk of
mg every symptoms including diarrhea. insomnia, lacks
morning Variable oral bioavailability. Oral significant cardiovascular
solution contains alcohol. effects.
Discontinuation symptoms may Good choice for initial
occur absent tapering. treatment of depression
in most older adults.
Fluoxetine 5 to 10 mg 5 to 60 mg daily Activating. Activating effect may be

every Significant drug interactions. useful for treatment of
morning depressed patients with
Prolonged half-life and active
low energy or
metabolites require weeks to
hypersomnia. Tapering
reach steady state, prolonging
upon discontinuation is
time needed to evaluate effect of
not needed due to long
dose adjustment and complicating
half-life.
wash-out and withdrawal.
Paroxetine 10 mg 10 to 40 mg every Weakly anticholinergic. May cause Useful for patients with
every evening constipation, dry mouth, or insomnia. Moderate half-
evening drowsiness. life with no active
Associated with more severe metabolites.
discontinuation symptoms in
absence of tapering.
Fluvoxamine 25 mg 25 to 200 mg Significant drug interactions. Short May be useful for

every every evening half-life associated with patients with insomnia.
evening discontinuation symptoms in
absence of tapering.
Serotonin-norepinephrine reuptake inhibitors (SNRIs) ◊
Venlafaxine 37.5 mg 75 to 225 mg once Applies to venlafaxine and Applies to venlafaxine

(extended once daily daily desvenlafaxine: and desvenlafaxine:
release) Activating. Activating effect may be
Venlafaxine 18.75 to 75 to 150 mg twice May cause dose-dependent useful for treatment of
(immediate 37.5 mg daily increases in blood pressure melancholic depressed
release) every (primarily diastolic) and heart patients with low energy
morning or rate. Monitor blood pressure or hypersomnia.
twice daily regularly. Useful for patients with
Desvenlafaxine 50 mg 50 mg every Gastrointestinal symptoms (eg, comorbid painful
every morning nausea) may be more prominent conditions such as
morning with immediate-release diabetic neuropathy.
CrCl <30 mL/min:
CrCl <30 50 mg every other venlafaxine.
mL/min: day Associated with discontinuation
50 mg symptoms absent tapering. Taper
every desvenlafaxine by increasing

other day interval between doses.
Duloxetine 10 to 20 20 to 60 mg once Significant drug interactions. Mildly sedating. Low risk

mg daily daily of insomnia.
Useful for patients with
comorbid painful
conditions such as
diabetic neuropathy or
chronic pain.
Atypical antidepressants ◊
Mirtazapine 7.5 mg 15 to 60 mg every Prolonged half-life and active Sedating. Low risk of
every evening metabolites. Risk of accumulation sexual dysfunction.
evening with renal and/or hepatic Appetite stimulant and
insufficiency. Dose reductions antinausea effects can
necessary. be noted within days.
Drowsiness, weight gain. Rare Useful for patients with
reports of agranulocytosis. insomnia or who may
benefit from weight
gain.
Bupropion 75 mg in 150 mg in morning Avoid in seizure disorders and Stimulant effect may be
sustained morning and midafternoon depressed patients with agitation. useful for treatment of
release initially (twice daily) Dose-dependent increase in depressed patients with
then twice diastolic blood pressure. May low energy and apathy.
daily worsen insomnia. Low risk of cognitive
toxicity. Dopaminergic
action may be
advantageous for
depressed patients with
Parkinson disease.
Vilazodone 10 mg 20 to 40 mg once Take with food to assure Low incidence of weight

once daily daily with food bioavailability. gain or sexual
with food Diarrhea, nausea, vomiting, dysfunction.
for seven dizziness, insomnia. Role in therapy for
days or treatment of depressed
Significant drug interactions via
more older adults or adults
CYP 3A4 require dose adjustment.
with comorbid illness is
not yet defined.
Trazodone 12.5 to 25 25 to 100 mg Sedation, orthostatic hypotension, Used in low doses as

mg taken taken 30 to 60 nausea. Residual daytime sedation adjunct to SSRI for
30 to 60 minutes before and cognitive impairment. Reports treatment of insomnia.
minutes bedtime for of hyponatremia.
before hypnotic effects;
bedtime antidepressant
for effects require
hypnotic higher doses
effects
Tricyclic antidepressants (TCAs) §
Nortriptyline 10 mg 10 to 100 mg Applies to nortriptyline and Applies to nortriptyline:

every every evening or in desipramine: Established therapeutic
evening two divided doses May be poorly tolerated by serum concentration 50
medically ill and older adults due to 150 ng/mL.
to anticholinergic effects that Mildly sedating. Taken at
include dry mouth, constipation, bed time for depressed
urinary retention, or altered vision patients with insomnia.
(eg, avoid in prostatic disease or
May be useful for
narrow angle glaucoma).
melancholic, anxious,
May be fatal in overdose. depressed patients who
Potentially cardiotoxic, can cause have not responded to
arrhythmia or orthostatic
hypotension. first- and second-line

Significant drug interactions. antidepressants.
Desipramine 10 mg 25 to 150 mg Applies to desipramine:

every every morning or Established therapeutic
morning in two divided serum concentration 125
doses to 300 ng/mL.
Mild stimulant effects
may be useful for
depressed patients with
low energy and
hypersomnia who have
not responded to first-
and second-line
antidepressants.
CYP: cytochrome.
* Specific interactions of antidepressants with other medications may be determined using the Lexi-Interact™ drug
interactions program included with UpToDate.
¶ For additional information refer to topic on unipolar depression in adults and SSRIs.
Δ Maximum recommended daily dose of citalopram is 20 mg for patients >60 years of age, with significant hepatic
insufficiency, or taking interacting medications that can increase citalopram levels.
◊ For additional information refer to topic on SNRIs and other antidepressants for treating depressed adults.
§ For additional information refer to topic on tricyclic and tetracyclic antidepressants for treating depressed adults.
Drug properties of monoamine oxidase inhibitor antidepressants and dosages in

the elderly (see note)
Drug Starting dose Dose range for older adult
Isocarboxazid 10 mg every morning 10 to 40 mg per day in divided doses
Phenelzine 7.5 mg every morning 22.5 to 60 mg per day in three

divided doses
Tranylcypromine 10 mg every morning 10 to 40 mg per day in divided doses
Selegiline (transdermal patch) 6 mg/24 hours applied once daily 6 to 12 mg/24 hours applied once
daily
IMPORTANT NOTE: MAOIs are NOT first line antidepressant medications due to the dietary restrictions, drug-drug
interactions and potentially severe side-effects. MAOIs are rarely used in medically ill or older adults except when
previously initiated and tolerated in the patient who is treatment resistant to all other antidepressants. For specific
drug interactions see the Lexi-Interact program included with UpToDate. For additional information, refer to the
separate topic on MAOIs for treating depressed adults.
MAOI: monoamine oxidase inhibitors.
Contributor Disclosures
Randall T Espinoza, MD, MPH Nothing to disclose Jürgen Unützer, MD, MPH Nothing to disclose Peter P
Roy-Byrne, MD Employment: Mass Medical Society (Journal Watch). Kenneth E Schmader,
MD Grant/Research/Clinical Trial Support: GlaxoSmithKline [Herpes zoster]. David Solomon, MD Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.
Conflict of interest policy

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Diagnosis and management of late-life unipolar

Risk factors for late-life depression include [23]:

● Recent onset of physical illness

Medical comorbidity — Treatment of depression can have beneficial effects on health

● A modified diagnosis of major depressive disorder and a past history of depression

Psychiatric comorbidity — Comorbidity of depressive illness with other psychiatric

Other risk factors for suicide include [47,49,50]:

● Comorbid physical illness

Subsequent dementia — Late life depression is associated with an increased risk of

● A meta-analysis of 23 prospective, community based, observational studies included more

Minor depression — Minor depression (subsyndromal depression) is diagnosed in patients with

Psychotic depression — Unipolar major depression with psychotic features (delusions or

Vascular depression — Cerebrovascular disease may increase an older person's vulnerability

Alzheimer disease and other dementias — The development of depression as a complication of

● Concurrent medical illness with overlapping symptoms of depression (fatigue, psychomotor

● Medication side effects overlapping depression symptoms

● Impaired communication skills in the elderly

● Patient presentation with multiple somatic complaints

● Patient's reluctance to acknowledge psychological distress due to perceived stigma of mental

● Mood or somatic symptoms out of proportion to what is expected

• Are you basically satisfied with your life?

• Do you often get bored?

• Do you often feel helpless?

• Do you feel pretty worthless the way you are now?

● Assessment for psychotic symptoms, hopelessness, insomnia, and malnutrition.

● Consideration of other medical conditions commonly associated with depressive symptoms,

● Determination of a family history of depression and family response to medication. Older

First-line treatment of depression consists of psychotherapy and somatic therapy (medication or

recommend pharmacotherapy. For chronic forms of depression, the combination of

● A meta-analysis of 15 randomized trials compared antidepressants with placebo in 4756

Psychotherapy — Psychotherapy is a useful but frequently underutilized treatment for elderly

Short-term treatments include cognitive-behavioral therapy (CBT), interpersonal psychotherapy,

● Another 12-week trial compared problem-solving therapy with supportive therapy in 74

Medication selection and management — A systematic review of 26 randomized trials that

● Paroxetine (10 to 40 mg per day) plus monthly interpersonal psychotherapy – 35 percent

Discontinuing antidepressants may be prompted by tachyphylaxis or side effects, or by the need to

Additional information about continuation and maintenance treatment is discussed separately.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) — Serotonin-norepinephrine

Atypical antidepressants — Atypical antidepressants include agomelatine, bupropion, and

Bupropion is generally considered an activating agent, so it may be useful in patients who

Serotonin modulators — Serotonin modulators include nefazodone, trazodone, and

Tricyclic and tetracyclic antidepressants — While no longer considered first or second-line

Monoamine oxidase inhibitors (MAOIs) — This class of antidepressants is rarely used

Methylphenidate — For patients with late-life major depression, simultaneously prescribing an

Aripiprazole — For patients with treatment-resistant late-life depression, adjunctive

Information about adjunctive second-generation antipsychotics for the general population of

Quetiapine — Although monotherapy with the second-generation antipsychotic quetiapine may

Other — Cognitive impairment in late-life depression raises the question as to whether

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

Epidemiology and diagnosis

● Depression associated with cerebrovascular disease is characterized by psychomotor

recommended. (See 'Psychotherapy' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

5. Unützer J. Clinical practice. Late-life depression. N Engl J Med 2007; 357:2269.

7. Crystal S, Sambamoorthi U, Walkup JT, Akincigil A. Diagnosis and treatment of depression

8. Unützer J, Katon W, Callahan CM, et al. Depression treatment in a sample of 1,801

15. Castro-Costa E, Dewey M, Stewart R, et al. Prevalence of depressive symptoms and

38. Frasure-Smith N, Lespérance F, Juneau M, et al. Gender, depression, and one-year

85. Vataja R, Pohjasvaara T, Mäntylä R, et al. Depression-executive dysfunction syndrome in

88. Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in

Total _ = _ + _ + _ + ___