depression in later life: is it time for prevention? charles f. reynolds Ⅲ,m.d. intervention...
TRANSCRIPT
DEPRESSION IN LATER LIFE:DEPRESSION IN LATER LIFE:IS IT TIME FOR PREVENTION?IS IT TIME FOR PREVENTION?
Charles F. Reynolds Ⅲ,M.D.Charles F. Reynolds Ⅲ,M.D.
Intervention Research Center forIntervention Research Center for
Late-Life Mood DisordersLate-Life Mood Disorders
Department of PsychiatryDepartment of Psychiatry
University of Pittsburgh School of MedicineUniversity of Pittsburgh School of Medicine
Support: National Institute of Mental Health , Forest Laboratories, GlaxosmithKlincSupport: National Institute of Mental Health , Forest Laboratories, GlaxosmithKlinc
THE RROSPECT STUDYTHE RROSPECT STUDY
Prevention of Suicide In Primary Prevention of Suicide In Primary
Care Elderly: Collaborative TrialCare Elderly: Collaborative Trial
Cornell
University of Pennsylvania
University of Pittsburgh
Late-life Depression: Late-life Depression: Causes and EffectsCauses and Effects
Disease
Disability
Psychosocial
Stressors
Genetics
Depression
SuicideAnxiolytie Dependence, Alcoholism
Cognitive Impairment DisabilityMedical Symptoms
Health Care Utilization
Mortality
A PUBLIC HEALTH RATIONALE FOR A PUBLIC HEALTH RATIONALE FOR PREVENTIVE TREATMENT OF PREVENTIVE TREATMENT OF
DEPRESSION IN OLD AGEDEPRESSION IN OLD AGE
• Depression in old age Depression in old age
- is common- is common
- has serious health consequences- has serious health consequences
- contributes to global burden of illness - contributes to global burden of illness related related
disabilitydisability
- is a risk factor for suicide- is a risk factor for suicide
- is a relapsing, recurrent, and chronic - is a relapsing, recurrent, and chronic illnessillness
FACTORS CONTRIBUTING TOFACTORS CONTRIBUTING TO RELAPSING CHRONIC ILLNESS COURSE RELAPSING CHRONIC ILLNESS COURSE
IN LATE LIFE DEPRESSIONIN LATE LIFE DEPRESSION
• • Psychosocial factors:Psychosocial factors:
- Role transitions, bereavement, increasing - Role transitions, bereavement, increasing
dependency, interpersonal conflictsdependency, interpersonal conflicts
• • Progressive depletion of psychosocial Progressive depletion of psychosocial resourcesresources
• • Chronic sleep disturbancesChronic sleep disturbances
• • Risk factors for cerebrovascular diseaseRisk factors for cerebrovascular disease
• • Neurodegenerative disordersNeurodegenerative disorders
• • Limited access to adequate treatmentLimited access to adequate treatment
Prevalence of Late-life Depression by Prevalence of Late-life Depression by Health/Independence StatusHealth/Independence Status
0
10
20
30
40
50
60
70
CommunityResidents
Chronically inPrimay CareOutpatients
HospitalizedPatient
Cognitively IntactNursing Home
Patients
Per
cen
t
Data represent a composite of multiple status
Major Depression Depressive Symptoms
Goals Of TreatmentGoals 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:PROSPECT GOAL:
• To test the effectiveness of an To test the effectiveness of an intervention in preventing and intervention in preventing and reducing:reducing:
• • Suicidal ideation and behaviorSuicidal ideation and behavior
• • HopelessnessHopelessness
• • Depressive symptomatologyDepressive symptomatology
in a representative sample of older in a representative sample of older patients in primary care.patients in primary care.
BACKGROUND:BACKGROUND:
• The elderly have the highest suicide rates in The elderly have the highest suicide rates in US.US.
• Old white males are at the greatest risk.Old white males are at the greatest risk.• Late life suicide victims typically see their Late life suicide victims typically see their
primary care physicians in the month prior to primary care physicians in the month prior to death.death.
• The majority of older suicide victims have had The majority of older suicide victims have had their first depressive episode in late life.their first depressive episode in late life.
• Although effective treatments exit, depression Although effective treatments exit, depression is often not detected or treated by the primary is often not detected or treated by the primary care physician.care physician.
PROSPECT’S INTERVENTION:PROSPECT’S INTERVENTION:GUIDELINE MANAGEMENTGUIDELINE MANAGEMENT
Identification of Diagnosis
Physician Education Patient & Family Psycho-Education
DEPRESSION SPECIALIST
TREATMENT ALGORITHM&
FEATURES OF TREATMENT ALGORITHMFEATURES OF TREATMENT ALGORITHM
• The algorithm is based on AHCPR Practice Guideline The algorithm is based on AHCPR Practice Guideline for the Treatment of Depression in Primary Care.for the Treatment of Depression in Primary Care.
• The algorithm is modified for treatment of the elderly The algorithm is modified for treatment of the elderly at the primary care office.at the primary care office.
• Guidelines use psychopharmacological (SSRI), Guidelines use psychopharmacological (SSRI), psychosocial, and other interventions based on psychosocial, and other interventions based on individual needs.individual needs.
• Psychiatric consultation is offered in complex cases.Psychiatric consultation is offered in complex cases.
• The guidelines encompass Acute, continuation, and The guidelines encompass Acute, continuation, and Maintenance Treatment.Maintenance Treatment.
• The paths address a wide range of syndromes ranging The paths address a wide range of syndromes ranging from mild to very severe depression.from mild to very severe depression.
SUBJECT SELECTION:SUBJECT SELECTION:
GOALS: GOALS: 1.Obtain a sample representative of practice population 1.Obtain a sample representative of practice population 2.Over-sample patients with depression and the very old 2.Over-sample patients with depression and the very old
DESIGN: DESIGN: Use a stratified , two stage random sampling strategyUse a stratified , two stage random sampling strategy
Total Practice
Age 60-74 Age 75+
50% of
Age 60-74
100% of
Age 75+
CES-D < 11CES-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 PRACTIVESPRIMARY CARE PRACTIVES
SELECTION:SELECTION:
• Primary care practices selected in pairs, similar onPrimary care practices selected in pairs, similar on • • location (urban vs. suburban)location (urban vs. suburban) • • Degree of academic affiliationDegree of academic affiliation • • Ethnic an racial composition of patients Ethnic an racial composition of patients
RANDOMIZATION:RANDOMIZATION:• Within pairs, practices randomly assigned to:Within pairs, practices randomly assigned to: • • low level intervention (“enhanced care”)low level intervention (“enhanced care”) • • high level intervention (“guideline management”)high level intervention (“guideline management”)
New York Philadelphia
Pittsburgh
LONGITUDINAL DESIGN:LONGITUDINAL DESIGN:PATIENT ASSESSMENTSPATIENT ASSESSMENTS
0 244 8 12 16 20
Baselin
e
Follow
-up
Telephon
e Telephon
e Telephon
e Follow
-u
p
Telephone
months
Summary of PROSPECT Data on Sampling and Summary of PROSPECT Data on Sampling and ScreeningScreening 4/1/024/1/02
81,185 patient appointments81,185 patient appointments -- 16,704 sampled for CESD screening-- 16,704 sampled for CESD screening
54.2% were eligible and completed screening54.2% were eligible and completed screening 27.6% refused screening27.6% refused screening 7.5% were ineligible7.5% were ineligible
Of 9,136 CESD’s completed, 1,107(11.4%) screened positive.Of 9,136 CESD’s completed, 1,107(11.4%) screened positive.
Patients who screened positive plus a 5% sample of screened Patients who screened positive plus a 5% sample of screened negative patients were invited to participate in the study.negative patients were invited to participate in the study.
In addition to the sampled patients, 68 patients who were not In addition to the sampled patients, 68 patients who were not sampled were invited to participate in the study.sampled were invited to participate in the study.
Summary of PROSPECT Data on Assessments Summary of PROSPECT Data on Assessments 4/1/024/1/02
1,276 sampled and referred patients have 1,276 sampled and referred patients have completed baseline assessment.completed baseline assessment.
By using a high cut off score on the By using a high cut off score on the CESD(>20),PROSPECT was able to optimize CESD(>20),PROSPECT was able to optimize its specificity(.925).its specificity(.925).
428(33.5%) met SCID/DSM-IV criteria for 428(33.5%) met SCID/DSM-IV criteria for major depressionmajor depression
256(20.1%) had treatable minor depression256(20.1%) had treatable minor depression
PROSPECT Enrollment DataPROSPECT Enrollment Data
Total enrollment: 1276 subjects, including 874 white and 347 blackTotal enrollment: 1276 subjects, including 874 white and 347 black889 women and 365 men889 women and 365 men
Of 1313 patients who signed consent, 329(25.1%) terminated from all participation Of 1313 patients who signed consent, 329(25.1%) terminated from all participation in the study(including 28 prior to completing the baseline interview).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 Mortality: 49 PROSPECT subjects have died, 1 by suicide (gun shot) and 48 by natural causesnatural causes
Psychiatric hospitalization: 11Psychiatric hospitalization: 11
Refusal of further participation: 133Refusal of further participation: 133
Treatment discontinuation due to supervening medical problems or dementia: 332Treatment discontinuation due to supervening medical problems or dementia: 332
PROSPECT Hypothesis TestingPROSPECT Hypothesis Testing
HYPOTHESIS:HYPOTHESIS:Compared to usual care, PROSPECT intervention is Compared to usual care, PROSPECT intervention is
associated at four months follow-up with a greater associated at four months follow-up with a greater reduction in depression, defined by 50% reduction reduction in depression, defined by 50% reduction in HDRS scores(“response”) and by absolute in HDRS scores(“response”) and by absolute change in HDRS scores.change in HDRS scores.
TESTING:TESTING:Mixed effect logistic regression and binary models forMixed effect logistic regression and binary models forbinary and continuous outcomes;binary and continuous outcomes;Radon effects corresponded to the primary care Radon effects corresponded to the primary care
practicepractice
PROSPECT 4-Month OutcomesPROSPECT 4-Month Outcomes
• Overall, and at each site , the response rate was Overall, and at each site , the response rate was greater in intervention versus usual care greater in intervention versus usual care practices(41.1% versus 27.4%) in unadjusted practices(41.1% versus 27.4%) in unadjusted (p<.028) and adjusted (p<.024) analyses.(p<.028) and adjusted (p<.024) analyses.
• Factors that were also significantly associated Factors that were also significantly associated with response included baseline diagnosis (MDD with response included baseline diagnosis (MDD versus minor), gender, and study site.versus minor), gender, and study site.
• The PROSPECT intervention was associated with a The PROSPECT intervention was associated with a significantly greater decrease in HDRS scores(-7.3 significantly greater decrease in HDRS scores(-7.3 vs –3.7) in both unadjusted (p<.001) and vs –3.7) in both unadjusted (p<.001) and adjusted (p<.001) analyses.adjusted (p<.001) analyses.
PROSPECTPROSPECT
• Total Depression Remission RateTotal Depression Remission Rate
• • (202/331 =61.03%)(202/331 =61.03%)
• CaucasianCaucasian
• • (161/238 =67.65%)(161/238 =67.65%)
• African AmericanAfrican American
• • (33/73 =45,21%)(33/73 =45,21%)
Remission Rates in Depressed Primary Care Remission Rates in Depressed Primary Care Elderly: PROSPECT Intervention PracticesElderly: PROSPECT Intervention Practices
• 94/126(74.6%) subjects who entered treatment 94/126(74.6%) subjects who entered treatment remittedremitted
• 22/126 dropped out 22/126 dropped out ¹¹¹ 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 Depression Remission Rates in Primary Care Primary Care
Elderly:PROSPECT Elderly:PROSPECT Usual Care PracticesUsual Care Practices
• 23/86 (27%) intention to treat23/86 (27%) intention to treat
• 23/58 (40%) completer23/58 (40%) completer
(Reynolds et al., unpublished PROSPECT data, June 2001)
Remission Rate in Elderly Depressed Remission Rate in Elderly Depressed Patients:Patients:
Primary Care Versus Mental Health SectorPrimary Care Versus Mental Health Sector
• Primary care: 94/126(74.6%) Primary care: 94/126(74.6%) 11 • Specialty Mental Health: 101/129(78%) Specialty Mental Health: 101/129(78%) 22
63/116(54%) 63/116(54%) 33
11 PROSPECT (MH59381) PROSPECT (MH59381)
22 Maintenance Therapies in Late-Life Depression(MH43832) Maintenance Therapies in Late-Life Depression(MH43832)
33 Nortriptyline vs Paroxetine(MH52247) Nortriptyline vs Paroxetine(MH52247)
PROSPECTPROSPECTPercent with Suicide Ideation(Hamilton Item)Percent with Suicide Ideation(Hamilton Item)
Among Depressed Patients(N=135)Among Depressed Patients(N=135)
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
Baseline 4 months 5 months 12 months
Control
Intervention
HD
RS
Su
icid
e
Item
PROSPECTPROSPECTPercent with Suicide Ideation(SSI>0)Percent with Suicide Ideation(SSI>0)Among Depressed Patients(N=133)Among Depressed Patients(N=133)
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
Baseline 4 months 5 months 12 months
Control
Intervention
SS
I>0
PROSPECT SignificancePROSPECT Significance
PROSPECT seeks to test the effectiveness of PROSPECT seeks to test the effectiveness of its intervention in older primary care its intervention in older primary care patients whose clinical and demographic patients whose clinical and demographic characteristics suggest high risk for characteristics suggest high risk for suicide.suicide.
Response, Remission, Recovery, Response, Remission, Recovery, Relapse,Relapse,
Recurrence & ChronicityRecurrence & Chronicity
‘Normalcy’
Symptoms
Syndrome
Remission
ResponseRelapse
Recovery
Recurrence
Incomplete
recovery
Chronicity
Treatment phases
Acute Continuation
MaintenanceTime
Severl
ty
Kupfer,1991
pro
gre
ssion
to
diso
rder
Risk of RecurrenceRisk of Recurrence
• Angst,1990 75%Angst,1990 75%
• Ernst & Angst,1992 80-90%Ernst & Angst,1992 80-90%
• Kessler, 1994 80-90%Kessler, 1994 80-90%
• Prien,1984 80%Prien,1984 80%
• Lee & Murray, 1988 95%Lee & Murray, 1988 95%
• Frank & Kupfer,1990 80%Frank & Kupfer,1990 80%
Survival Analysis: Recurrence Rates of Major Depressive Survival Analysis: Recurrence Rates of Major Depressive EpisodesEpisodes
Cu
mu
lati
ve P
rop
ort
ion
Wit
h N
o
Recu
rren
ce
Weeks in Maintenance
Reynolds et al., JAMA 1999; 281(1):39-45.
Social Adjustment ScaleSocial Adjustment Scale
-30
-25
-20
-15
-10
-5
0
5
10
Med
ian
%
ch
an
ge
groupPlanned contrast, F (1.46)=7.15, r=0.18, p=0.01
Lenze, Dew et al., American Journal of Psychiatry,2002
Survival Analysis: Recurrence Survival Analysis: Recurrence Rates Rates
of Major Depression Episodeof Major Depression EpisodeC
um
ula
tive P
rop
ort
ion
Wit
h N
o R
ecu
rren
ce
Weeks in Maintenance
Reynolds et al., JAMA 1999; 281(1);39-45
Survival Analysis: Recurrence Survival Analysis: Recurrence Rates Rates
of Major Depression Episodeof Major Depression EpisodeC
um
ula
tive P
rop
ort
ion
Wit
h N
o R
ecu
rren
ce
Weeks in Maintenance
Reynolds et al., JAMA 1999; 281(1);39-45
Survival Analysis – Time to Relapse/Recurrence Survival Analysis – Time to Relapse/Recurrence on Paroxetine/Nortriptyline Continuation on Paroxetine/Nortriptyline Continuation
PharmacotherapyPharmacotherapy
Months in continuation Treatment
Cu
mu
lati
ve P
rop
ort
ion
Wit
h N
o R
ecu
rren
ce
Bump.Mulart et al., Depression and Anxiety 13:38-44,2001
Time to Recurrence of Major Depressive Episodes in Time to Recurrence of Major Depressive Episodes in MTLD-Ⅱ: Preliminary DataMTLD-Ⅱ: Preliminary Data
Surv
ival D
istr
ibuti
on
Fu
nct
ion
Weeks from Randomization
Mean Time to Recurrence of Major Mean Time to Recurrence of Major DepressiveDepressive
Episodes in MTLD-Ⅱ: Preliminary DataEpisodes in MTLD-Ⅱ: Preliminary Data
ParoxetinParoxetinee
(n=52)(n=52)
77 weeks77 weeks
PlaceboPlacebo
(n=43)(n=43)
43 weeks43 weeks
Maintenance Therapies in Late Life Depression:Maintenance Therapies in Late Life Depression:Optimizing and Maintaining Cognitive FunctioningOptimizing and Maintaining Cognitive Functioning
N=200 N=50
Cit+DONN=70-80
Cit+PBON=70-
80
Elderly Depressed Subjects
Elderly Non-Depressed
Treatment with CIT
8 Weeks: With Venlat if HRSD<30%
12 weeks: With Ven if HRSD>10
Response:HRSD 17<=10
Treatment up to 2 years
Cognitive Assignment:
T1: Post-depression treatment
T2: 3 Months
T3: 12 months
T4: 24 months
POSSIBLE APPROACHES TO PRIMARY POSSIBLE APPROACHES TO PRIMARY PREVENTION OF DEPRESSION PREVENTION OF DEPRESSION
IN OLD AGE IN OLD AGE
APPROACHES TO PRIMARY APPROACHES TO PRIMARY PREVENTION --RATIONALEPREVENTION --RATIONALE
• Certain groups of elderly persons are at high risk for Certain groups of elderly persons are at high risk for developing new onset or recurrent depression:developing new onset or recurrent depression:
- Bereavement- Bereavement
- Care giving- Care giving
- Chronic insomnia- Chronic insomnia
- Medically ill- Medically ill
۰۰ Especially myocardial infarction, stroke, high Especially myocardial infarction, stroke, high cerebrovascular risk burden, macular degeneration, cerebrovascular risk burden, macular degeneration, osteoarthritis, cancerosteoarthritis, cancer
- Early dementia- Early dementia
- Early signs of depression- Early signs of depression
HOPE: Risk Reduction HOPE: Risk Reduction With ACE InhibitionWith ACE Inhibition
-40
-35
-30
-25
-20
-15
-10
-5
0
CVD death Nor MI Stroke CABG/PTCA New-onsetdiabetes
*P<.0001
↑P=.002
The HOPE Study Investigation. N Engl J Med. 2000:342:145-153
%
25%*
20%*
31%*
16%*
32%*
What is practiced?What is practiced?
Geriatric depression is linked to:Geriatric depression is linked to:
• increased utilization of health care increased utilization of health care servicesservices
• More frequent use of multiple medicationsMore frequent use of multiple medications
• Longer hospital staysLonger hospital stays
• Increased demands on nursing home timeIncreased demands on nursing home time
• Under treatment in primary careUnder treatment in primary care
TYPES OF APPROACHES TO PRIMARY TYPES OF APPROACHES TO PRIMARY PREVENTION-OPPORTUNITIESPREVENTION-OPPORTUNITIES
FOR PREVENTIONFOR PREVENTION
• Pharmacotherapy or cognitive behavioral therapy Pharmacotherapy or cognitive behavioral therapy of chronic insomniaof chronic insomnia
• Problem solving therapy or CBT for patients with Problem solving therapy or CBT for patients with chronic medical disorders and disabilitychronic medical disorders and disability
• Social rhythm therapy for recently bereaved Social rhythm therapy for recently bereaved elderlyelderly
• Information, affective self-management, stress Information, affective self-management, stress management, and education in health sleep management, and education in health sleep practices for Alzheimer care giverspractices for Alzheimer care givers
What is known?What is known?
• Geriatric depression responds well to Geriatric depression responds well to treatment.treatment.
• There is a relatively low rate of treatment There is a relatively low rate of treatment resistance to adequate treatment.resistance to adequate treatment.
• Maintenance therapies work to prevent Maintenance therapies work to prevent recurrence.recurrence.
• There is much treatment response There is much treatment response variability.variability.