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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 • • • • • 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: • • • • • 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.