Transcript Late-life Depression: Causes and Effects

DEPRESSION IN LATER LIFE:
IS IT TIME FOR PREVENTION?
Charles F. Reynolds Ⅲ,M.D.
Intervention Research Center for
Late-Life Mood Disorders
Department of Psychiatry
University of Pittsburgh School of Medicine
Support: National Institute of Mental Health , Forest Laboratories, GlaxosmithKlinc
THE RROSPECT STUDY
Prevention of Suicide In Primary
Care Elderly: Collaborative Trial
Cornell
University of Pennsylvania
University of Pittsburgh
Late-life Depression: Causes
and Effects
Suicide
Anxiolytie Dependence,
Alcoholism
Disease
Disability
Psychosocial
Stressors
Genetics
Depression
Cognitive Impairment
Disability
Medical Symptoms
Health Care Utilization
Mortality
A PUBLIC HEALTH RATIONALE FOR
PREVENTIVE TREATMENT OF
DEPRESSION IN OLD AGE
• Depression in old age
- is common
- has serious health consequences
- contributes to global burden of illness related
disability
- is a risk factor for suicide
- is a relapsing, recurrent, and chronic illness
FACTORS CONTRIBUTING TO
RELAPSING CHRONIC ILLNESS COURSE
IN LATE LIFE DEPRESSION
• Psychosocial factors:
- Role transitions, bereavement, increasing
dependency, interpersonal conflicts
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•
•
•
•
Progressive depletion of psychosocial resources
Chronic sleep disturbances
Risk factors for cerebrovascular disease
Neurodegenerative disorders
Limited access to adequate treatment
Prevalence of Late-life Depression by
Health/Independence Status
70
60
Percent
50
40
30
20
10
0
Community
Residents
Major Depression
Chronically in
Primay Care
Outpatients
Hospitalized
Patient
Depressive Symptoms
Data represent a composite of multiple status
Cognitively Intact
Nursing Home
Patients
Goals Of Treatment
• Mortality and health care
costs
• Depressive symptoms
• Relapse and recurrence
• Quality of life
• Medical health status
NIH consensus Conference on Diagnosis and Treatment of Depression
In Late Life. JAMA. 1992;268:1018
PROSPECT GOAL:
• To test the effectiveness of an intervention
in preventing and reducing:
• Suicidal ideation and behavior
• Hopelessness
• Depressive symptomatology
in a representative sample of older patients
in primary care.
BACKGROUND:
• The elderly have the highest suicide rates in US.
• Old white males are at the greatest risk.
• Late life suicide victims typically see their
•
•
primary care physicians in the month prior to
death.
The majority of older suicide victims have had
their first depressive episode in late life.
Although effective treatments exit, depression is
often not detected or treated by the primary
care physician.
PROSPECT’S INTERVENTION:
GUIDELINE MANAGEMENT
Identification of
Diagnosis
DEPRESSION
SPECIALIST
Physician Education
&
Patient & Family
Psycho-Education
TREATMENT
ALGORITHM
FEATURES OF TREATMENT ALGORITHM
• The algorithm is based on AHCPR Practice Guideline for the
•
•
•
•
•
Treatment of Depression in Primary Care.
The algorithm is modified for treatment of the elderly at the
primary care office.
Guidelines use psychopharmacological (SSRI), psychosocial,
and other interventions based on individual needs.
Psychiatric consultation is offered in complex cases.
The guidelines encompass Acute, continuation, and
Maintenance Treatment.
The paths address a wide range of syndromes ranging from
mild to very severe depression.
SUBJECT SELECTION:
GOALS: 1.Obtain a sample representative of practice population
2.Over-sample patients with depression and the very old
DESIGN: Use a stratified , two stage random sampling strategy
Total Practice
Age 60-74
Age 75+
50% of
100% of
Age 60-74
Age 75+
CES-D < 11
CES-D
> 11
10%
100%
Identify age-eligible,
Community dwelling
patients
Screen by telephone
with CES-D
Results of screen
Interview in person
with SCID
PRIMARY CARE PRACTIVES
SELECTION:
• Primary care practices selected in pairs, similar on
• location (urban vs. suburban)
• Degree of academic affiliation
• Ethnic an racial composition of patients
RANDOMIZATION:
• Within pairs, practices randomly assigned to:
• low level intervention (“enhanced care”)
• high level intervention (“guideline management”)
New York
Philadelphia
Pittsburgh
0
4
8
12
16
20
24 months
Baseline
Telephone
Telephone
Follow-up
Telephone
Telephone
Follow-up
LONGITUDINAL DESIGN:
PATIENT ASSESSMENTS
Summary of PROSPECT Data on Sampling and Screening 4/1/02
81,185 patient appointments
-- 16,704 sampled for CESD screening
54.2% were eligible and completed screening
27.6% refused screening
7.5% were ineligible
Of 9,136 CESD’s completed, 1,107(11.4%) screened positive.
Patients who screened positive plus a 5% sample of screened negative
patients were invited to participate in the study.
In addition to the sampled patients, 68 patients who were not sampled
were invited to participate in the study.
Summary of PROSPECT Data on Assessments
4/1/02
1,276 sampled and referred patients have
completed baseline assessment.
By using a high cut off score on the
CESD(>20),PROSPECT was able to optimize its
specificity(.925).
428(33.5%) met SCID/DSM-IV criteria for major
depression
256(20.1%) had treatable minor depression
PROSPECT Enrollment Data
Total enrollment: 1276 subjects, including 874 white and 347 black
889 women and 365 men
Of 1313 patients who signed consent, 329(25.1%) terminated from all participation
in the study(including 28 prior to completing the baseline interview).
Mortality: 49 PROSPECT subjects have died, 1 by suicide (gun shot) and 48 by
natural causes
Psychiatric hospitalization: 11
Refusal of further participation: 133
Treatment discontinuation due to supervening medical problems or dementia: 332
PROSPECT Hypothesis Testing
HYPOTHESIS:
Compared to usual care, PROSPECT intervention is
associated at four months follow-up with a greater
reduction in depression, defined by 50% reduction in
HDRS scores(“response”) and by absolute change in
HDRS scores.
TESTING:
Mixed effect logistic regression and binary models for
binary and continuous outcomes;
Radon effects corresponded to the primary care practice
PROSPECT 4-Month Outcomes
• Overall, and at each site , the response rate was greater
•
•
in intervention versus usual care practices(41.1% versus
27.4%) in unadjusted (p<.028) and adjusted (p<.024)
analyses.
Factors that were also significantly associated with
response included baseline diagnosis (MDD versus
minor), gender, and study site.
The PROSPECT intervention was associated with a
significantly greater decrease in HDRS scores(-7.3 vs –
3.7) in both unadjusted (p<.001) and adjusted (p<.001)
analyses.
PROSPECT
• Total Depression Remission Rate
• (202/331 =61.03%)
• Caucasian
• (161/238 =67.65%)
• African American
• (33/73 =45,21%)
Remission Rates in Depressed Primary Care
Elderly: PROSPECT Intervention Practices
• 94/126(74.6%) subjects who entered treatment remitted
• 22/126 dropped out ¹
¹ Reasons for attrition:
death(n=1)
Relocation(n=2)
medical problem(n=1)
severe psychiatric complications(n=4)
treatment refusal(n=12)
other(n=2)
(Reynolds et al., unpublished PROSPECT data, June 2001)
Depression Remission Rates in
Primary Care Elderly:PROSPECT
Usual Care Practices
• 23/86 (27%) intention to treat
• 23/58 (40%) completer
(Reynolds et al., unpublished PROSPECT data, June 2001)
Remission Rate in Elderly Depressed Patients:
Primary Care Versus Mental Health Sector
• Primary care:
94/126(74.6%) 1
• Specialty Mental Health: 101/129(78%) 2
63/116(54%)
1 PROSPECT (MH59381)
2 Maintenance Therapies in Late-Life Depression(MH43832)
3 Nortriptyline vs Paroxetine(MH52247)
3
PROSPECT
Percent with Suicide Ideation(Hamilton Item)
Among Depressed Patients(N=135)
30.0%
25.0%
20.0%
Control
15.0%
Intervention
10.0%
5.0%
0.0%
Baseline 4 months 5 months 12 months
PROSPECT
Percent with Suicide Ideation(SSI>0)
Among Depressed Patients(N=133)
30.0%
25.0%
20.0%
Control
15.0%
Intervention
10.0%
5.0%
0.0%
Baseline
4 months
5 months 12 months
PROSPECT Significance
PROSPECT seeks to test the effectiveness of its
intervention in older primary care patients
whose clinical and demographic characteristics
suggest high risk for suicide.
Response, Remission, Recovery, Relapse,
Recurrence & Chronicity
Recovery
Remission
Relapse
Response
Recurrence
Severlty
‘Normalcy’
Incomplete
recovery
Symptoms
Syndrome
Treatment phases
Chronicity
Acute
Time
Continuation
Maintenance
Kupfer,1991
Risk of Recurrence
• Angst,1990
• Ernst & Angst,1992
• Kessler, 1994
75%
80-90%
80-90%
• Prien,1984
• Lee & Murray, 1988
• Frank & Kupfer,1990
80%
95%
80%
Cumulative Proportion With No Recurrence
Survival Analysis: Recurrence Rates of Major Depressive Episodes
Weeks in Maintenance
Reynolds et al., JAMA 1999; 281(1):39-45.
Social Adjustment Scale
10
5
0
-5
-10
-15
-20
-25
-30
group
Planned contrast, F (1.46)=7.15, r=0.18, p=0.01
Lenze, Dew et al., American Journal of Psychiatry,2002
Survival Analysis: Recurrence Rates
of Major Depression Episode
Weeks in Maintenance
Reynolds et al., JAMA 1999; 281(1);39-45
Survival Analysis: Recurrence Rates
of Major Depression Episode
Weeks in Maintenance
Reynolds et al., JAMA 1999; 281(1);39-45
Survival Analysis – Time to Relapse/Recurrence on
Paroxetine/Nortriptyline Continuation Pharmacotherapy
Months in continuation Treatment
Bump.Mulart et al., Depression and Anxiety 13:38-44,2001
Survival Distribution Function
Time to Recurrence of Major Depressive Episodes in MTLD-Ⅱ:
Preliminary Data
Weeks from Randomization
Mean Time to Recurrence of Major Depressive
Episodes in MTLD-Ⅱ: Preliminary Data
Paroxetine
(n=52)
77 weeks
Placebo
(n=43)
43 weeks
Maintenance Therapies in Late Life Depression:
Optimizing and Maintaining Cognitive Functioning
Elderly Depressed Subjects
Elderly Non-Depressed
N=200
Treatment with CIT
N=50
Cognitive Assignment:
8 Weeks: With Venlat if
HRSD<30%
12 weeks: With Ven if
HRSD>10
T1: Post-depression treatment
Response:HRSD 17<=10
Cit+DON
N=70-80
Cit+PBO
N=70-80
T2: 3 Months
Treatment up to 2 years
T3: 12 months
T4: 24 months
POSSIBLE APPROACHES TO PRIMARY
PREVENTION OF DEPRESSION
IN OLD AGE
APPROACHES TO PRIMARY PREVENTION
--RATIONALE
• Certain groups of elderly persons are at high risk for
developing new onset or recurrent depression:
- Bereavement
- Care giving
- Chronic insomnia
- Medically ill
۰ Especially myocardial infarction, stroke, high
cerebrovascular risk burden, macular degeneration,
osteoarthritis, cancer
- Early dementia
- Early signs of depression
HOPE: Risk Reduction
With ACE Inhibition
0
-5
CVD death
Nor MI
Stroke
CABG/PTCA
-10
%
New-onset
diabetes
-15
16%*
-20
-25
-30
-35
20%*
25%*
31%*
-40
*P<.0001
↑P=.002
The HOPE Study Investigation. N Engl J Med. 2000:342:145-153
32%*
What is practiced?
Geriatric depression is linked to:
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increased utilization of health care services
More frequent use of multiple medications
Longer hospital stays
Increased demands on nursing home time
Under treatment in primary care
TYPES OF APPROACHES TO PRIMARY
PREVENTION-OPPORTUNITIES
FOR PREVENTION
• Pharmacotherapy or cognitive behavioral therapy of
•
•
•
chronic insomnia
Problem solving therapy or CBT for patients with chronic
medical disorders and disability
Social rhythm therapy for recently bereaved elderly
Information, affective self-management, stress
management, and education in health sleep practices for
Alzheimer care givers
What is known?
• Geriatric depression responds well to treatment.
• There is a relatively low rate of treatment
•
•
resistance to adequate treatment.
Maintenance therapies work to prevent
recurrence.
There is much treatment response variability.