LATE-LIFE DEPRESSION: PROGRESS AND HOPE
From Scripps Clinic’s 23rd Annual Primary Care Medicine: A Practical Approach
David Naimark, MD, Associate Clinical Professor of Psychiatry, University of California, San Diego, School of
Medicine
| Introduction: presentation focuses on 3 areas; 1) advances in psychiatry made in field of late-life depression, eg,
identification of cerebrovascular etiology; 2) screening tools useful for diagnosing late-life depression in primary
care; 3) treatment of geriatric depression
|
 | Depression: “perhaps the most frequent cause of emotional suffering in later life and significantly decreases
quality of life in older adults” (Daniel Blazer, President of American Geriatric Society in 2003)
|
| Significance of late-life depression: increases—morbidity; disability; premature death; suicide (biggest cause
of suicide among elderly white men); predicted that by 2020—depression will be second only to heart disease as
cause of disability and premature death
|
| Obstacles to treatment: neither patient nor health care professional may recognize symptoms (often presents
with irritability and mental status changes, rather than sadness)
|
| Key areas of progress: recognition of importance of vascular disease; subsyndromal depression (presentation
differs from classic major depressive episode, but produces equivalent functional impairment in elderly)
|
| Sentinel event: depression should be viewed as sentinel event that substantially increases risk for decline in general
health and functioning
|
| Two types of late-life depression: traditional use of term— for depression that presents for first time in late life;
vascular risk factors—most common cause of late-life depression; depression present in earlier life that persists
into old age much less sensitive to vascular risk factors and more commonly driven by family history and genetics
|
| Common misconception: natural for elderly with many medical problems to be depressed (may lead to unhappiness,
which differs from clinical depression; most elderly adults relatively content; losses in old age usually fairly
well tolerated; positive personality changes often occur; spirituality and religion become bigger issues; even demented
patient in nursing home should experience pleasure (if not, depression present)
|
| Old stress-vulnerability model: trait such as neuroticism results in vulnerability to life circumstances (eg, poverty,
chronic illness in family, grief over loss, burden of caregiving), leading to depression in later life
|
| New biologic-etiology model: comorbidity with medical illness; vascular risk factors; microvascular infarcts in
frontal lobes (striatum and deep white matter) produce susceptibility to depression for first time in late life;
striatofrontal deficits related to onset of dementia; pseudodementia—appears to be dementia but caused by underlying
depression; ≈85% of patients treated for pseudodementia with antidepressants go on to develop dementia;
accounts for most late-life depression
|
| Comorbid medical illness: increases risk of depression; factors that elevate risk—heart disease; stroke; cancer;
thyroid disease; Alzheimer’s disease; living alone; being widowed; lacking confidant; stressful life events
|
| Interplay of dementia and cognitive impairment: depression related to perception of cognitive capacities
eroding, especially at early stages (may provoke suicide); white matter and subcortical abnormalities; high cortisol
levels in dementia risk factor for developing depression
|
| Medications contributing to depression: reserpine; benzodiazepines; estrogen; progesterone; vinblastine; vincristine;
α-methyldopa; cimetidine; clonidine; corticosteroids; digitalis; hydralazine; propoxyphene; propranolol;
tamoxifen
|
| Primary prevention: reduce vascular risk factors—smoking; alcohol intake; cardiovascular disease; hypertension;
diabetes mellitus; obesity
|
| Suicide rates: increase with age, more sharply in those 70 to 74 yr of age; especially high in white men; more
likely due to depression than in young; majority of patients recently visited primary care physician before suicide
|
| Method of suicide: firearms, 73% in people ≥65 yr of age
|
| Risk factors for suicide: depression, male sex, use of highly fatal method, alcoholism, comorbid physical illness, living
alone, being widowed, lacking confidant, and stressful life event
|
| Risk factors for late-life depression: female sex; male sex (special considerations, eg, suicide); prior episode
of major depression; history of depressive illness in first-degree relative (bipolar depression increases risk ≈5-
fold); chronic medical illnesses
|
| Depressive subtype: mixed depression and anxiety characteristic of late-life depression; most medications for
depression also effective for anxiety disorders
|
| Criteria for major depressive episode: from Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition (DSM-IV); ≥5 symptoms during same 2-wk period, representing change from previous functioning; ≥1
symptom either depressed mood or loss of interest or pleasure (anhedonia); ≥ 4 of following neurovegetative
signs—appetite or weight changes; insomnia or hypersomnia; psychomotor agitation or retardation; fatigue; recurrent
thoughts of death or suicide; feelings of worthlessness or inappropriate guilt; diminished ability to think,
concentrate, or make decisions; late-life depression—normally subsyndromal, not major depression
|
| Clues for depression in primary care: persistent complaints of somatic problems without identifiable etiology
(eg, pain; headache; fatigue; insomnia; gastrointestinal symptoms; arthritis; multiple diffuse symptoms; weight
loss); frequent calls and visits; high utilization of services
|
| Clues for depression in hospitalized patients: delayed recovery (commonly after coronary artery bypass graft
[CABG], myocardial infarction [MI], or stroke); treatment refusal; rehabilitation refusal; discharge problem
|
| Other clues: failure to thrive; agitation
|
| Differential diagnosis: underlying medical cause, eg, thyroid dysfunction, Parkinson’s disease, dementia, pancreatic
carcinoma (depression presenting complaint); history of manic episode
|
| Diagnostic considerations: dysthymic disorder—≥ 2 yr of predominantly depressed mood; common presentation
in geriatric depression; minor depressive disorder—problems present for ≥2 wk; mood disturbance with >2
but <5 target symptoms; symptoms do not meet criteria for major depression (similar to subsyndromal depression);
bereavement—≈15% of patients with bereavement develop major depressive disorder; bereaved older
people less likely to develop depressive symptoms; if functional impairment present, treatment indicated, even if
symptoms do not meet strict criteria; sleep disturbance—relatively common in older people; can be presenting
sign of depression; strongly associated with depression in community-residing elderly; may be indicator of relapse
in patients in remission from depresson
|
| Vascular depression: frontostriatal-limbic dysfunction; executive dysfunction
|
| Depression-executive dysfunction syndrome: psychomotor retardation; anhedonia; absence of preoccupation
with guilt (common factor in regular depression); less pronounced vegetative symptoms; absence of psychotic
features; family history less likely; diminished response to standard pharmacotherapies (therapies for dementia
under investigation)
|
| Executive functioning problems: inability to plan, sequence, and organize activities (characteristic deficit in dementia
and vascular depression); easy test—clock-drawing test; gauges ability to draw clock, and put in numbers
and hour and minute hands
|
| Physiology: prefrontal and subcortical lesions, probably due to microinfarcts; white matter infarcts visible on
magnetic resonance imaging (MRI); depression risk higher with apolipoprotein E4 (apoE4) alleles
|
| Poststroke depression: occurs in 20% to 50% of patients; most likely when stroke involves left cerebral pole of
left hemisphere
|
| Screening for depression: screening instruments under investigation in research institutions
|
| Research protocols: current emphasis away from efficacy trials (specialized patient populations) to focus on effectiveness
trials (more typical patients and shorter instruments)
|
| Center for Epidemiologic Studies-Depression Scale (CES-D): 20-item instrument (10-item version for use
in community); validated cross-culturally; can be self-administered; difficult to use in long-term care
populations; not validated in dementia
|
| Geriatric Depression Scale (GDS): 2 versions (30-item and 15-item); yes-or-no format; easy to score; administered
by patient or caregiver; validated in mild dementia; can differentiate geriatric depression from dementia
|
| Patient Health Questionnaire: PHQ-9—9-item instrument based on DSM-IV criteria for depression; good diagnostic
accuracy; high sensitivity; reliable measure of severity; currently used in Improving Mood–Promoting Access
to Collaborative Treatment for Late Life Depression (IMPACT) study as outcome measure; PHQ-2—2-item
scale; sensitive for depression; not specific as to variant; consists of first 2 items of PHQ-9 (feeling down, depressed,
or hopeless? little interest or pleasure in doing things?); sensitive for depression in older patients
|
| Cornell Scale for Depression in Dementia: used for patients with depression in context of dementia; takes ≈10
min with patient and 20 min with caregiver; 19-item scale; grades severity
|
| Useful questions: for depression—are you sad? are you sleeping poorly; do you worry too much? what have you
enjoyed doing lately? have you been bothered by little interest or pleasure in doing things? for anxiety—are you
feeling nervous? older patients more comfortable with word “nervous,” rather than “anxious”; for suicidal
ideation—have you felt life not worth living? did you ever wish you could go to sleep and not wake up? is that
something you’ve thought about recently? have things reached the point that you’ve thought about harming yourself?
|
| Treatment: every study shows combination of psychopharmacologic and psychotherapeutic interventions works
better than either alone; psychotherapy—effectiveness of psychotherapeutic intervention depends less on specific
therapy than on skill and perception of caring of person doing it (eg, priest, rabbi, primary care physician, friend);
antidepressants—all effective; data show some more beneficial in certain areas; venlafaxine (Effexor) for restoring
patient to level of functioning before depression; duloxetine (Cymbalta) for somatic syndromes (eg, chronic
pain syndromes, diabetic neuropathy); selective serotonin reuptake inhibitors (SSRIs) have better data for geriatric
depression; clinical reasons for choice of agent—patient had good response in past; family member had good
response; patient has positive perception of agent
|
| Approaches to therapy in academic centers
|
| Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) approach:
|
| Stage 1: 6 to 12 wk trial of SSRI (sertraline used)
|
| Stage 2: 6 to 12 wk trial of previously successful antidepressant
|
| Stage 3: failed initial trial; augment with bupropion if partial response; augment with lithium if partial response
to tricyclic antidepressant (TCA); switch to venlafaxine, TCA, bupropion, or alternative SSRI (citalopram
[Celexa] used)
|
| Stage 4: 2 failed antidepressant trials; venlafaxine or nortriptyline (eg, Pamelor), augmented with lithium
|
| Stage 5: multiple treatment failures; SSRI with nortriptyline for 6 to 8 wk; or electroconvulsive therapy (ECT) or
monoamine oxidase (MAO) inhibitor
|
| Preventing Suicide in Elderly Patient Collaborative Trial (PROSPECT): multicenter trial; focus on care managers;
preliminary response good
|
| Initial therapy: citalopram, 10 mg, increasing to 30 mg for 12 wk; switch to other SSRI if history of previous
response; switch to bupropion (≤300 mg/day) if unable to tolerate citalopram
|
| IMPACT: intervention centered in primary care office, with videotapes, booklets, and evaluation by depression
case manager; primary care physicians wrote all antidepressant prescriptions; combination of depression case
manager and primary care physician found highly effective
|
| Alternative treatment strategy: although SSRIs viewed as first-line agents, with dual-acting agent as second-
line (eg,TCA, venlafaxine, citalopram), not necessary to start with SSRI; speaker may begin with dual-acting
agent in some cases, eg, previous good response to TCA, or remission or pain control important
|
| Conclusion: without treatment, “many of our senior citizens will live their final years in despair and suffering,
without any appreciation of their affliction or the understanding and comfort of those most dear to them”; avoid
nihilistic attitude; difficult patient may defy expectations and respond well to aggressive therapy
|
| Questions and answers: effective dose—regardless of initial dose, to achieve effectiveness, elderly ultimately require
same antidepressant dose as younger patients; acceptance of diagnosis—if patient reluctant to accept diagnosis
of depression, explain that antidepressants shown effective therapy for other conditions that patient may prefer
as diagnosis, eg, chronic fatigue syndrome, fibromyalgia, chronic pain syndromes; dysthymia—usually comorbid
with personality disorder or substance abuse disorder; data limited but suggest that in absence of comorbidity, antidepressants
helpful when given over longer time and at higher doses than for major depression; therapy for chronic
pain disorders—low-dose TCAs proven effective in past; unwanted side effects avoided by using dual-acting
agent, eg, venlafaxine, duloxetine, citalopram; effect of dopamine levels on depression—unknown; bupropion increases
dopamine levels in brain; mechanism of benefit unknown for dopamine or other neurotransmitters (eg, serotonin,
norepinephrine); according to current thinking, interplay among 3 neurotransmitters more important than
levels; alternatively, benefits may depend on balance of processes within neuron (neurotransmitters act primarily
outside cell, in synaptic cleft); benefits of altering abnormal hormonal levels—eg, important to screen for abnormal
thyroid levels; antidepressant therapy ineffective if underlying hormonal abnormality untreated; relation of
growth factors to depression—major area of research; depression may be related to shrinkage in area of limbic
system; antidepressants targeting growth factors under development
|
Suggested Reading
Alexopoulos GS et al: Clinical presentation of the "depression executive dysfunction syndrome" of late life. Am J Geriatr
Psychiatry 10:98, 2002; Cannon DS et al: The PHQ-9 as a brief assessment of lifetime major depression. Psychol
Assess 19:247, 2007; Cheung YB et al: Performance of the CES-D and its short forms in screening suicidality and hopelessness
in the community. Suicide Life Threat Behav 37:79, 2007; Kraus CA et al: Use of cognitive behavioral therapy
in late-life psychiatric disorders. Geriatrics 62:21, 2007; Lyness JM et al: The clinical significance of subsyndromal depression
in older primary care patients. Am J Geriatr Psychiatry 15:214, 2007; Schulberg HC et al: Best clinical practice:
guidelines for managing major depression in primary medical care. J Clin Psychiatry 60 (Suppl 7):19, 1999; Steffens
DC et al: The Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) approach. Psychopharmacol Bull
36:58, 2002; Unutzer J et al: IMPACT Investigators. Improving Mood-Promoting Access to Collaborative Treatment.
Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA
288:2836, 2002; Vataja R et al: Depression-executive dysfunction syndrome in stroke patients. Am J Geriatr Psychiatry
13:99, 2005.
Web Sites for Copies
| Geriatric Depression Scale: standford.edu/~yesavage/GDS.html
|
| Patient Health Questionnaire: pdhealth.mil/guidelines/download/appendix2.pdf
|
| Cornell Screen: mqa.dhs.state.tx.us/qmweb/depression/htm
|
Educational Objectives
| The goal of this program is to improve the diagnosis, and treatment of late-life depression. After hearing and assimilating
this program, the clinician will be better able to:
|
| Identify common misconceptions about depression in the elderly.
|
| Employ the new biologic-etiology model in approaching the diagnosis and treatment of depression in older patients.
|
| Recognize risk factors for late-life depression.
|
| Choose among several screening instruments for identifying late-life depression.
|
| Implement recent strategies for treating patients with late-life depression.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant financial
relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved
to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this
program, the following has been disclosed: Dr. Naimark —Eli Lilly, Astra, Wyeth, Forest (Speakers’ Bureaus)
Acknowledgements
Dr. Naimark was recorded at 23rd Annual Primary Care Medicine: A Practical Approach, sponsored by Scripps Clinic,
August 11-13, 2007, in San Diego, CA. The Audio-Digest Foundation thanks Dr. Naimark and the Scripps Clinic for their cooperation
in the production of this program.
|
