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The Association between Late-life
Depression and Medical Illness
Maria D. Llorente MD
Professor
Dept. of Psychiatry & Behavioral Sciences
Miller School of Medicine
at the University of Miami
The “Graying” of America
 By the year 2025, the world’s older
population
(60 and older) will approach 1.2 billion.
 By the year 2030, 1 of every 5 people in
the U.S. will be 65 or older.
 Older Americans will number more than 65
million
Late-Life Depression
• Incidence of major depression declines with age,
but minor depression is much more common
• Depressive symptoms occur in 15%–25% of older
adults (>65 years) that fail to meet criteria but
cause distress and interfere with functioning
• Fewer than half of depressed seniors are
recognized as being depressed and of those
who are identified fewer than half receive
treatment
U.S. Dept of Health and Human Services. Mental Health: A Report of the Surgeon General.
Rockville, MD: U.S. Dept of Health and Human Services, Substance Abuse and Mental Health
Services Administration, Center for Mental Health Services, NIH, NIMH, 1999.
Primary Care is the De Facto
Mental Health System (in the
United States) responsible for the
care of more patients with mental
disorders than the specialty
mental health sector.
Regier et al. Arch Gen Psychiatry 1993; 50:85-94
Epidemiology of Major Depression
• 16.2% of US population report at least one lifetime episode
• More than half of patients have first episode by age 40
• 25% of older cancer patients
• 25-50% of post-stroke patients
• 1/3 of Alzheimer’s patients
• 50% of Parkinson’s patients
• 30% of post-MI Patients
Depression Guideline Panel. Depression in Primary Care: Vol 1. Detection and Diagnosis. Clinical Practice
Guideline No. 5. Rockville, MD: US Dept of Health and Human Services. Public Health Service, Agency for
Health Care Policy and Research; no. 93-0550; 1993. Kessler RC et al. J Affect Disord. 1993;29:85-96.
Kessler et al., JAMA 2003; Evans et al., J Clin Psych 1999; Astrom et al., Stroke, 1993; Tiller et al.,
Psychopharm 1992; Meaf et al., Neurology 1994; Cumming Am J Psych 1992.
Minority Elderly
and Depression
•
•
•
•
HISPANIC
>65 will increase by more
than 450% by 2050
Depressive disorder
prevalence in primary care
increased from 4.5% to 8.6%
between 1992-97
Higher prevalence of
depressive symptoms (1140%)
Higher depression-associated
mortality from both suicide
and medical disorders
AFRICAN-AMERICAN
• >65 will increase by 131% by
2030
• Lower rates of depression
recognition and treatment
• Poorer medical outcomes
associated with comorbid
depression (EX: diabetes and
stroke/hyperglycemia/renal
failure/hypertriglyceridemia)
Major Depression Is Associated
with Chronic Medical Illness
30
6%–25%
25
20
Prevalence
of Major
Depression (%)
6%–14%
15
5%–10%
10
5
2%–4%
0
Community
Primary Care
Clinic
Medical
Inpatient
Setting
Katon W, Schulberg H. Gen Hosp Psychiatry. 1992;14:237-247.
Rosen J, Mulsant BH, Pollock BG. Nursing Home Med. 1997;5:156-165.
Nursing
Home
Impact of Untreated Depression:
Morbidity & Mortality
• Patient morbidity
– Poorer health outcomes
– Suicide attempts
– Accidents
– Lost jobs
– Alcohol Use & Abuse
– Marital Problems
• Mortality
– Older white men have
highest suicide rates
– Fatal accidents
– Death due to related
medical complications
• Societal costs
– Caregiver burden
– Higher medical costs
– Increased healthcare
utilization
Preskorn SH. Outpatient Management of Depression: A Guide for the Primary Care Practitioner. 2nd
ed. Caddo, OK: Professional Communications, Inc.; 1999: Chapter 2.
Comparison of Physical and Social
Functioning in Other Medical Illnesses
Depression impairs physical and social functioning significantly more than these
medical illnesses
100
*
95
Social or
Physical
Functioning
Score†
Physical Function
Social Function
*
90
*
*
85
*
*
*
*
80
75
70
0
Depressive
Disorder
* P <0.05 vs depressive disorder.
† Score of 100 = perfect functioning.
Wells KB et al. JAMA. 1989;262:914-919.
Hypertension
Diabetes
Arthritis
No Chronic
Condition
Medical Outcomes and Depression
Major Depression:
Post-MI Survival
OR = 3.6
% Cardiac Mortality
25
20
15
10
5
00
Depressed (N=35)
Non-depressed (N=187)
6
12
18
months
Frasure-Smith, Lesperance, 1998
Major Depression and
Congestive Heart Failure
• More severe medical illness and more
functional impairment than nondepressed (Freedman 2001)
• Utilize more inpatient/outpatient medical
services than non-depressed (Koenig, 1998)
Major Depression and
Congestive Heart Failure
• Associated with increased risk of
functional decline or death at 6 month f/u
(Vaccarino, 2001)
• Depression is significant predictor of
mortality in clinically stable CHF patients
(Murberg, 1999)
• Greater severity of depression associated
with 3-fold increased risk of mortality at 1
year f/u than non-depressed
(Jiang, 2001)
Major Depression and
Diabetes Mellitus
• 28% of sample reported moderately
severe symptoms of depression and/or
anxiety
• Significant association between
depressive symptoms and high Hgb A1C
in men
• 1/3 reported they’d like counseling
Lloyd et.al. Diabet Med 2000 Mar;17(3):198-202
Major Depression and
Diabetes Mellitus
• Medline and PsycINFO databases and
published reference lists were used to identify
studies that measured the association of
depression with glucose control.
• A total of 24 studies satisfied the inclusion and
exclusion criteria for the meta-analysis.
• Depression was significantly associated with
hyperglycemia (Z = 5.4, P < 0.0001).
Lustman et.al. Diabetes Care 2000 Jul;23(7):934-42
Major Depression and
Diabetes Mellitus
• 183 African-American men with diabetes
• 30% had significant depressive symptoms
(CES-D >22)
• Greater depressive symptoms significantly
associated with higher serum levels of cholesterol
and triglycerides (P<0.050).
Gary et.al. Diabetes Care 2000 Jan;23(1):23-9
Medical Illness, Depression and
Suicide
• Record-linkage of 2323 suicides among 1.9 million
people 50 and older in Denmark showed that
neoplasms, circulatory/respiratory and digestive
diseases confer increased risk; infections,
nutritional, metabolic diseases increased risk for
hospitalized men; did not control for mood
disorders (Erlangsen et al; JAGS 2005)
• Pulmonary disease, cancer, visual impairment and
neurological disorder confer risk after adjusting for
mood disorders (Waern et al; BMJ 2002)
Suicide Rates By Age & Gender
(Per 100,000)
70
CDC. National Center for Health Statistics; 2000
60
50
40
30
0
20
20
40
10
60
80
0
WHITE M
WHITE F
85+
AA M
AA F
Suicide and
Lifetime Axis I Diagnosis By Age
100
80
60
40
20
0
21-54
55-74
75
Affective syndromes
Other (primary psychosis, ETOH, substance, etc)
No diagnosis
Conwell, Am J Psychiatry, 1994
Reasons for Underdiagnosis of Late-life
Depression in Primary Care
• Over-identification with the patient
• Lack of time
• Lack of training in mental health
• False belief that older adults won’t respond to
treatment
• Atypical symptoms in older adults
DSM-IV-TR Criteria for
Major Depression
Sleep:
 5 Symptoms in the same 2-week period
Insomnia or
hypersomnia
Interest*:Depressed mood*
Guilt:
Energy:
Concentration: Diminished
ability to think or
make decisions
Loss of interest*
Appetite:
Feelings of
worthlessness
Psychomotor: Psychomotor
Weight change
slowing or
agitation
Fatigue
Suicide:
Preoccupation
with death
* Must include 1 of these
DSM-IV-TR. Washington, DC: American Psychiatric Association. 2000.
Clinical Features of Late-life
Depression
• “Depression” without sadness
• Irritability
• Prominent Anxiety
• Cognitive complaints
• Prominent vague somatic complaints
• Unexplained health worries
• Heightened pain complaints
• Loss of interest and pleasure
• Social withdrawal or avoidance of social interactions
• Multiple primary care visits without resolution of the problem
• Unexplained functional decline
Early-onset v. Late-onset
Early-onset
Late-onset
• Index episode in childhood
or early adult life
• Index episode after age 50
• First degree relatives with
depression
• Chronic physical illness
• Less physical illness
• More psychiatric
comorbidity (SUD;
personality disorders)
• Sad mood
• Less genetic predisposition
• Poorer treatment response
with more chronic course
• Increased mortality
• Abnormal brain imaging
• Les psych comorbidity
• Apathy and anhedonia
Phases of Treatment for Depression
Remission
Relapse
Increased
severity
Euthymia
Symptoms
Recurrence
Relapse
Response
Syndrome
Treatment phases
Acute
(6–12 wk)
Time
Kupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28.
Continuation Maintenance
(4–9 mo)
( 1 yr)
Treatment Goal
The goal of treatment with either
antidepressant medication or
psychotherapy in the acute phase is the
remission of
major depressive disorder symptoms
APA Practice Guidelines for the Treatment of Psychiatric Disorders. 2000.
Pseudodementia
• Patients may present with complaints of loss of
memory
• Frequent “I don’t know responses” on exam
• Often a prodrome of dementing illness (as many as
50% may develop dementia within 5 years)
• If prodromal, usually late-onset, with prominent
psychomotor retardation and/or psychotic features
• Consider frequent neurocognitive testing, and early
use of cognitive-enhancing agents.
Vascular depression
• Frontostriatal disconnection/dysfunction (Executive
dysfunction – impairment in IADLs)
• Prominent psychomotor slowing and apathy
• Poorer response to treatment, higher risk of relapse
and recurrence
• Limited vegetative symptoms and little depressive
ideation
• Brain imaging abnormalities: enlarged ventricles,
white matter hyperintensities
Post-stroke depression
• 3-6 months after CVA
• 12-24 months after CVA
• Prominent vegetative
features
• Fewer vegetative
symptoms, more apathy
• Larger lesion volumes
• Associated with significant
social and physical
impairments
• Likely biological
pathogenesis
Depression with Psychosis
• 4% of depressed elderly
• 45% of psychiatrically hospitalized elderly
• Frequent and severe anxiety and agitation
• Somatic delusions common, but few hallucinations
• Nihilistic beliefs, hopelessness
• Often have suicidal ideations
• ECT indicated as first-line treatment
Minor Depression
• Subsyndromal Depression
• Associated with significant functional impairment
and disability, lower quality of life and increased
medical care utilization
• Associated with progression to depression at one
year follow-up
• DSM-IV-TR: qualitatively similar to major
depression, but only 2-4 symptoms needed
Caregiver Depression
• Often seen in those caring for older adult with
dementia
• Associated with changing roles, increased
responsibility, risk of social isolation, grief
surrounding loss of demented person
• Often fail to recognize stress/burden, but report
fatigue, insomnia, social withdrawal, and feeling
“burned out”
• Affects quality of caregiving
Caregiver Depression
Barriers to open discussion:
• Need to protect themselves from feelings of
disloyalty due to “complaining about” loved one
• May represent failure as caregiver
• Family already burdened with demented loved one,
don’t want to add to burden
• Fear of own feelings of anger, guilt, ambivalence
• Need to approach from the perspective of
enhancing the care provided
Family Intervention and
Nursing Home Placement
Cumulative proportion of
surviving patients
1
0.8
0.6
0.4
0.2
0
1
2
3
4
5
6
Survival time (year)
Mittelman, JAMA 1996
Treatment
Control
7
8
Bereavement
• Losses frequently encountered in late-life that lead to
bereavement
• Features that distinguish depression from bereavement:
•Guilt
•Suicidal thoughts
•Morbid preoccupation wit h worthlessness
•Psychomotor retardation
•Prolonged and marked functional impairment
•Complex hallucinations (not just thinking they heard
voice of loved one, or transiently saw their image
Comorbidity of Depression & Anxiety
• Nearly 3/4 of community-dwelling adults with
lifetime Major Depression also meet criteria for at
least 1 other DSM-IV diagnosis
• Most (59.2%) of these are anxiety disorders
Kessler et al., JAMA 2003
• 86% of older adults with anxiety disorders also met
criteria for a depressive disorder
PRISM-E, (Bartels et al, Am J Psych 2005)
Comorbidity of Depression & Anxiety
• In older adults, comorbid anxiety disorder and
depression is associated with:
- greater symptom severity
- poorer social functioning
- more difficult course of illness
- decreased or delayed treatment response
- higher level of suicidality
Angst 1999, Roy-Byrne 2000, Lenze 2000, 2001, Bartels 2002
Do Anxiety Symptoms Also Respond to
Antidepressant Medication Treatment?
Study Design
• A randomized, double-blind,
flexible-dose study
• 24 wk treatment
• Citalopram (Celexa) N = 52
• Paroxetine (Paxil) N = 52
• Dose range: 20–40 mg/d
• Outcome measures:
HAMD-24, HAMA
Inclusion Criteria
• Outpatients age18–65 years
• DSM-IV major depression and
mixed anxiety/depression
• HAMD-24 baseline score 18
for depressive symptoms
• HAMA baseline score 17 for
anxiety symptoms
Jefferson J, Greist JH. Poster presented at APA, 2001.
Effects on Depression:
Citalopram vs Paroxetine
Treatment Week
0 1 2
4
6
8
12
16
20
0
-4
HAMD-24
Mean Change
From Baseline
-8
-12
-16
-20
Jefferson J, Greist JH. Poster presented at APA, 2001.
Citalopram
20–40 mg/d
(n = 52)
Paroxetine
20–40 mg/d
(n = 52)
24
Effects on Anxiety:
Citalopram vs Paroxetine
Treatment Week
0 1 2
4
6
8
12
16
20
0
-4
HAMA
Mean Change
From Baseline
-8
-12
-16
Jefferson J, Greist JH. Poster presented at APA, 2001.
Citalopram
20–40 mg/d
(n = 52)
Paroxetine
20–40 mg/d
(n = 52)
24
Antidepressant Doses
Medication
Initial
Dose
(mg/d)
Usual Dose
Adult
Concerns
Geriatric
P450 interactions
10
25
20-40
100-250
10-20
75-150
10
10
10
20-60
20-60
10-20
20-40
20
10
Bupropion (Wellbutrin)
75
100-300
150
Seizures
Nefazodone (Serzone)
50
25-50
15
25
200-400
100-400
15-45
150-225
100-150
75-150
15-45
75-150
Hepatitis
Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Citalopram (Celexa)
Escitalopram (Lexapro)
P450 interactions
Anticholinergic
Somnolence
Nausea/insomnia/activation
OTHERS
Trazodone (Desyrel)
Mirtazapine (Remeron)
Venlafaxine (Effexor)
Anticholinergic
Somnolence
 BP
Hypotheses for Low Remission
Rates in Major Depression
• Patients satisfied with incomplete response
• Patients, clinicians do not expect remission
• Treatments may not be well tolerated
• Physicians not comfortable or familiar with
recommended optimal dosages
Keller MB, et al. Arch Gen Psychiatry. 1992;49:809-816.
Electro-convulsive therapy
Indicated in patients who:
• Are acutely suicidal
• Have major depression with psychotic features
• Have failed 2 adequate trials of antidepressants
• Cannot tolerate antidepressant tx
• Have previously responded to ECT and prefer this tx
Patients on average need 6-8 treatments
General Principles of Late-life
Depression Management
• Education for patient/family that meds are not
effective until patient has taken them for the right
amount of time (usually 3-6 weeks) in the right dose
• Start low, go slow, but go – need to reach
therapeutic dose
• Minimum duration is 9-12 months after symptom
remission for first episode
• Recommend long-term treatment in patients with 2
or more lifetime episodes
Evidence-based Management of
Late-life Depression
• Annual screening for depression in all patients
• Patients who screen positive are assessed within 6
weeks for a depressive disorder and/or suicidal ideas
• Those who assess positive require treatment with either
therapy/ medication alone or in combination
• At least 3 follow-up visits within first 3 months
• Index episode treated for at least 9-12 months
• Recurrent episode maintained on antidepressant longterm