DEPRESSION IN LATER LIFE: IS IT TIME FOR PREVENTION?

1. 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

2. THE RROSPECT STUDY Cornell University of Pennsylvania University of Pittsburgh Prevention of Suicide In Primary Care Elderly: Collaborative Trial

3. 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

5. 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

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

7. 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

8. 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.

9. 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.

10. PROSPECT’S INTERVENTION:GUIDELINE MANAGEMENT Physician Education Patient & Family Psycho-Education Identification of Diagnosis DEPRESSION SPECIALIST TREATMENT ALGORITHM &

11. 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.

12. 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 < 11 CES-D > 11 Results of screen Interview in person with SCID 10% 100%

13. 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

14. LONGITUDINAL DESIGN:PATIENT ASSESSMENTS 0 4 8 12 16 20 24 months Baseline Telephone Telephone Follow-up Telephone Follow-up Telephone

15. Summary of PROSPECT Data on Sampling and Screening4/1/02 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.

16. 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

17. 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

18. 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

19. 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.

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

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)

22. 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)

23. 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%) 3 1 PROSPECT (MH59381) 2 Maintenance Therapies in Late-Life Depression(MH43832) 3 Nortriptyline vs Paroxetine(MH52247)

24. PROSPECTPercent with Suicide Ideation(Hamilton Item)Among Depressed Patients(N=135) HDRS Suicide Item

25. PROSPECTPercent with Suicide Ideation(SSI>0)Among Depressed Patients(N=133) SSI>0

26. 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.

27. 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

28. 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%

29. 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.

30. Social Adjustment Scale Median % change group Planned contrast, F (1.46)=7.15, r=0.18, p=0.01 Lenze, Dew et al., American Journal of Psychiatry,2002

31. 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

32. 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

33. 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 13:38-44,2001

34. Time to Recurrence of Major Depressive Episodes in MTLD-Ⅱ: Preliminary Data Survival Distribution Function Weeks from Randomization

35. Mean Time to Recurrence of Major DepressiveEpisodes in MTLD-Ⅱ: Preliminary Data

36. Maintenance Therapies in Late Life Depression:Optimizing and Maintaining Cognitive Functioning Elderly Depressed Subjects Elderly Non-Depressed N=200 N=50 Treatment with CIT 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+DONN=70-80 Cit+PBON=70-80 T2: 3 Months T3: 12 months Treatment up to 2 years T4: 24 months

37. POSSIBLE APPROACHES TO PRIMARY PREVENTION OF DEPRESSION IN OLD AGE

38. 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

39. HOPE: Risk Reduction With ACE Inhibition % 16%* 20%* 25%* 31%* 32%* *P<.0001 ↑P=.002 The HOPE Study Investigation. N Engl J Med. 2000:342:145-153

40. 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

41. TYPES OF APPROACHES TO PRIMARY PREVENTION-OPPORTUNITIESFOR 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

42. 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.