DEPRESSION IN LATER LIFE: IS IT TIME FOR PREVENTION?

1
DEPRESSION IN LATER LIFEIS IT TIME FOR
PREVENTION?

• Charles F. Reynolds ?,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

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THE RROSPECT STUDY
Cornell University of Pennsylvania University of
Pittsburgh

• Prevention of Suicide In Primary
• Care Elderly Collaborative Trial

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Late-life Depression Causes and Effects
Suicide
Anxiolytie Dependence, Alcoholism
Disease Disability Psychosocial Stressors Genetics
Cognitive Impairment
Disability
Depression
Medical Symptoms
Health Care Utilization
Mortality
4
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

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FACTORS CONTRIBUTING TO RELAPSING CHRONIC
ILLNESS COURSE IN LATE LIFE DEPRESSION

• Psychosocial factors
• - Role transitions, bereavement, increasing
• dependency, interpersonal conflicts
• Progressive depletion of psychosocial
  resources
• Chronic sleep disturbances
• Risk factors for cerebrovascular disease
• Neurodegenerative disorders
• Limited access to adequate treatment

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Prevalence of Late-life Depression by
Health/Independence Status
Percent
Major Depression Depressive Symptoms
Data represent a composite of multiple status
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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.
19922681018
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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.

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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.

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PROSPECTS INTERVENTIONGUIDELINE MANAGEMENT
Physician Education
Patient Family Psycho-Education
Identification of Diagnosis
DEPRESSION SPECIALIST
TREATMENT ALGORITHM

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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.

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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
Identify age-eligible, Community dwelling patients
50 of Age 60-74
100 of Age 75
Screen by telephone with CES-D
CES-D lt 11
CES-D gt 11
Results of screen
Interview in person with SCID
10
100
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PRIMARY CARE PRACTIVESSELECTION

• 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)

Philadelphia
New York
Pittsburgh
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LONGITUDINAL DESIGNPATIENT ASSESSMENTS
0
24
4
8
12
16
20
months
Baseline
Telephone
Telephone
Follow-up
Follow-up
Telephone
Telephone
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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 CESDs 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.

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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(gt20),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

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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

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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

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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
  (plt.028) and adjusted (plt.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 (plt.001)
  and adjusted (plt.001) analyses.

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PROSPECT

• Total Depression Remission Rate
• (202/331 61.03)
• Caucasian
• (161/238 67.65)
• African American
• (33/73 45,21)

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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(n1)
Relocation(n2) medical problem(n1)
severe psychiatric complications(n4)
treatment refusal(n12) other(n2)
(Reynolds et al., unpublished
PROSPECT data, June 2001)
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Depression Remission Rates in Primary Care
ElderlyPROSPECT Usual Care Practices

• 23/86 (27) intention to treat
• 23/58 (40) completer
• (Reynolds et al., unpublished PROSPECT data, June
  2001)

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Remission Rate in Elderly Depressed
PatientsPrimary Care Versus Mental Health Sector

• Primary care 94/126(74.6) 1
• Specialty Mental Health 101/129(78) 2
• 
  63/116(54) 3
• 1 PROSPECT (MH59381)
• 2 Maintenance Therapies in Late-Life
  Depression(MH43832)
• 3 Nortriptyline vs Paroxetine(MH52247)

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PROSPECTPercent with Suicide Ideation(Hamilton
Item)Among Depressed Patients(N135)
HDRS Suicide Item
25
PROSPECTPercent with Suicide Ideation(SSIgt0)Amon
g Depressed Patients(N133)
SSIgt0
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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.

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Response, Remission, Recovery, Relapse,Recurrence
Chronicity
Recovery
Remission
Relapse
Recurrence
Response
Normalcy
Incomplete recovery
progression
to disorder
Symptoms
Severlty
Syndrome
Chronicity
Treatment phases
Acute
Continuation
Maintenance
Time
Kupfer,1991
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Risk of Recurrence

• Angst,1990 75
• Ernst Angst,1992 80-90
• Kessler, 1994 80-90
• Prien,1984 80
• Lee Murray, 1988 95
• Frank Kupfer,1990 80

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Survival Analysis Recurrence Rates of Major
Depressive Episodes
Cumulative Proportion With No Recurrence
Weeks in Maintenance
Reynolds et al., JAMA 1999 281(1)39-45.
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Social Adjustment Scale
Median change
group
Planned contrast, F (1.46)7.15, r0.18, p0.01
Lenze, Dew et al., American Journal of
Psychiatry,2002
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Survival Analysis Recurrence Rates of Major
Depression Episode
Cumulative Proportion With No Recurrence
Weeks in Maintenance
Reynolds et al., JAMA 1999 281(1)39-45
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Survival Analysis Recurrence Rates of Major
Depression Episode
Cumulative Proportion With No Recurrence
Weeks in Maintenance
Reynolds et al., JAMA 1999 281(1)39-45
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Survival Analysis Time to Relapse/Recurrence on
Paroxetine/Nortriptyline Continuation
Pharmacotherapy
Cumulative Proportion With No Recurrence
Months in continuation Treatment
Bump.Mulart et al., Depression and Anxiety
1338-44,2001
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Time to Recurrence of Major Depressive Episodes
in MTLD-? Preliminary Data
Survival Distribution Function
Weeks from Randomization
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Mean Time to Recurrence of Major
DepressiveEpisodes in MTLD-? Preliminary Data
Paroxetine (n52) 77 weeks
Placebo (n43) 43 weeks
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Maintenance Therapies in Late Life
DepressionOptimizing and Maintaining Cognitive
Functioning
Elderly Depressed Subjects
Elderly Non-Depressed
N200
N50
Treatment with CIT
Cognitive Assignment
8 Weeks With Venlat if HRSDlt30
12 weeks With Ven if HRSDgt10
T1 Post-depression treatment
ResponseHRSD 17lt10
CitDONN70-80
CitPBON70-80
T2 3 Months
T3 12 months
Treatment up to 2 years
T4 24 months
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POSSIBLE APPROACHES TO PRIMARY PREVENTION OF
DEPRESSION IN OLD AGE
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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
• ? Especially myocardial infarction,
  stroke, high cerebrovascular risk burden, macular
  degeneration, osteoarthritis, cancer
• - Early dementia
• - Early signs of depression

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HOPE Risk Reduction With ACE Inhibition

16
20
25
31
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Plt.0001 ?P.002 The HOPE Study Investigation. N
Engl J Med. 2000342145-153
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What is practiced?Geriatric depression is
linked to

• 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

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TYPES OF APPROACHES TO PRIMARY PREVENTION-OPPORTUN
ITIESFOR 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

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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.