Comparison of Depression Interventions after Acute Coronary Syndrome Funded by the National Heart Lung and Blood Institute RC2-HL HL-101663 Depressive Symptoms are Related to Acute Coronary Events Increased risk of ACS recurrence/mortality Independent of traditional risk factors Reduced long-term survival (up to 5-years) 5 post ACS Dose-dependent Highly prevalent 35-45 % of with elevated depressive symptoms Risk occurs at a relatively low level of depressive symptoms (Beck Depression inventory I score of > 10) 1 2 Adjusted Depressive symptoms in CHD patients and All-cause mortality Post-MI Depressive symptoms and cardiac mortality Barth J, Shumacher M, & Herrmann-Lingen H. Psychosomatic Medicine, 2004. vanmelle et al., Psychosomatic Medicine 2004
Survival free of cardiac mortality, Cumulative % Survival Free of Cardiac Mortality Patients with Unstable Angina or Non-Fatal MI, Cumulative % 100% 95% 90% 85% 80% 0 N=430 100 200 300 Time After Discharge for Unstable Angina, Days BDI < 10 BDI > 10 Odds Ratio = 4.7 (1.9 11.3) P< 0.001 400 Lespérance et al,, 2000 Long-term Survival Impact of Increasing Levels of Post-MI Depression (BDI Score) N=896 Time after discharge for MI, days Lesperance et al. Circulation. 2002 BDI < 4 BDI 4 to 9 BDI 10 to 18 BDI > 19 6 Depression Conceptualizations Current depression/ depressive symptoms Acute coronary disease event Depressive symptoms and 42-month MACE/ACM MACE/ACM risk time Assess current depression/ depressive symptoms Strata Low Depressive symptoms High Depressive symptoms 7 8
Depression Conceptualizations Persistent depressive symptoms Persistent depression and 42-month MACE/ACM Acute coronary disease event MACE/ACM risk time Assess current depression/ depressive symptoms Strata Non Depressed Remitted Depressed Persistent Depressed 9 10 Would you rather take medication or get counseling? A next trial needs to consider: An observation period to rule out those with remittent depressive symptoms Patients have differing psychosocial reasons for their depressive symptoms Note: sometimes people check both options, thus total is > 100% Medical patients are have strong preferences for, and against, both psychotherapy and medication to treat their depressive symptoms 11 12
Primary Outcome COPES 2 RCT Aims To explore in a depression intervention RCT the patient satisfaction and depressive symptom reduction of a patient-preference, preference, stepped-care model (problem- solving and antidepressant medication), as compared to usual cardiology care in patients with Acute Coronary Syndrome and persistent depressive symptoms. Funded by the National Heart Lung and Blood Institute N01-HC HC-25197 UC (n=77) INT (n=80) OR (95% CI) P Depression Care Rated as Excellent /very good at 3 mo 13.2 (6.5-19.6) 21.6 (12.9-29.7) 1.8 (0.8-4.5).18 Excellent /very good at 9 mo 18.8 (10.4-26.7) 54.2 (41.9-63.6) 5.4 (2.2-12.9) <.001 no care at 3 mo, No. (%) 56 (73.7) 53 (71.6) no care at 9 mo, No. (%) 43 (62.3) 19 (27.1) 13 14 Satisfaction with Depression Care Beck Depression Group Differences Variable UC INT INT vs UC Between-Group P Non-depressed (n=80) (n=77) (n=80) Difference BDI 3 mo 19.6 (18.2-21.1) 19.0 (17.5-20.4) 0.7 ( 2.7 to 1.4).52 2.8 (2.3-3.3) BDI 9 mo 17.7 (15.6-19.7) 13.2 (11.1-15.3) 4.5 ( 7.4 to 1.6).003 3.4 (2.4-4.3) Usual care (18%) vs Intervention (54%) Change 1.9 ( 3.8 to 0.1) 5.7 ( 7.6 to 3.8) 3.8 ( 6.5 to 1.2).005 0.5 ( 0.3 to 1.4) Effect size.59 16
Beck Depression Group Differences Average difference between groups on the BDI BDI-II II{ 17 A CREATE data for comparison between IPT (Intervention) and Clinical Management (Control) B CREATE data for comparison between Citalopram (Intervention) and Placebo (Control) Days to Major Adverse Coronary Event/Death by Group Status CODIACS Aims To determine the feasibility and effectiveness of the COPES intervention for depression in post- ACS patients at other sites; To obtain estimates of yield, acceptance, and retention for use in planning a large phase 3 clinical trial. Funded by the National Heart Lung and Blood Institute RC2-HL HL-101663 4% Intervention and 13% Usual care; log-rank test, χ 2 (1)=3.78; P=.048; 5 nondepressed patients had MACE (6%). 20
CODIACS Design CODIACS Organizational Chart Two-parallel arm assessor-blinded trial Randomization in 1:1 manner Active: Stepped care Control: Referred care 5-site single-blind randomized feasibility trial Sites: Columbia, Washington U, Emory, Yale, U Penn 21 22 CODIACS Endpoints CODIACS Inclusion criteria Satisfaction with depression care Depression scores (BDI) Hospitalized for acute coronary syndrome (ACS) in previous 2-42 4 months Beck Depression Inventory (BDI) score >10 and <15 on each of 2 occasions (1-2 2 weeks apart), or BDI>15 on one occasion Age >18 years 23
CODIACS Exclusions CODIACS CONSORT Inability to complete the baseline assessment within 2-42 months of the index ACS event; Presence of non-cardiovascular condition likely to terminate fatally within 1 year; Moderate/sever liver disease; Need for immediate psychiatric intervention (i.e., requiring hospitalization or psychiatric intervention within 72 hours); Major psychiatric co-morbidity including active psychosis, bipolar disorder, or overt personality disorder; dementia; active substance abuse or dependency; History of bipolar illness. 26 Statistical Considerations CODIACS Timeline With n=150, 80% chance of detecting difference in depression scores between groups of 0.46 SD-units (4 point difference in BDI). 27 28
Assessment Schedule Patient choice Step 1 Antidepressant (usually sertraline) Problem solving therapy (PST) Baseline Index ACS Screening Month 0 2-Month 4-Month 6-Month -4 to -2 mos -2 weeks Time=0 8 wks 16 wks 24 wks Medical history, depressive symptom assessment, consent Medical history, depressive assessment depressive assessment depressive assessment depressive assessment 6-8 weeks Step 2 6-8 weeks Step 3 Insufficient response options: Augment with PST Switch to different antidepressant type Full response: Maintenance Insufficient response options: Augment with PST Augment with other antidepressant Referral for other types of psychotherapy Insufficient response options: Augment with first line antidepressant Switch to first line antidepressant Switch to different antidepressant type Full response: Maintenance Insufficient response options: Augment with other antidepressant Referral for other types of psychotherapy Full response: Maintenance/Relapse prevention Full response: Maintenance/Relapse prevention 30 Decision Rules for Step Movement Initial PHQ9 Score Needed Improvement after 2 month to remain at Step 5-10 30% (score of 4-7) 4 11-20 50% (score of 6-10) 6 > 20 60% (score of 8-11) 8 Successful Treatment Patients who have a remission of symptoms (PHQ < 3 for 2 weeks) proceed to relapse prevention planning and maintenance treatment. If this occurs during PST, then the patient moves to a monitoring phase. This entails weekly phone contact for 2 weeks, then every 2 weeks for 4 weeks, then monthly. If PHQ9 remains < 3, then this is maintained. If PHQ9score is > 4 during these phone contacts, treatment is reinitiated. Patients on medication will continue until end of study and then be referred to continuous psychiatric care. 31 32
Stepped Care Referred Care Patient s s primary care provider informed in writing of elevated depressive symptoms Provider offers usual care treatment We follow for type of treatment offered Patient educated about the costs and benefits of choosing anti-depressant or therapy Patient chooses first step Every 6-86 8 weeks, depressive symptoms re- assessed, and treatment is intensified, augmented, or switched Maintenance phone calls occur when depression remission criteria met; treatment can be re-initiated. 33 34 Problem Solving Treatment (PST) Brief form of psychotherapy that teaches people how to solve the problems that are making them depressed. Collaborative care model: depression care specialist, primary care provider, patient. Treatment duration: 4-84 8 sessions, total treatment time 2.5-4.5 hours. Will be conducted by telephone if convenient for patient Medication Options Sertraline, citalopam, Or Bupropion (either history of no response to SSRI OR insufficient response to chosen SSRI in Step 1) Dosing suggestions for initial and incremental increases Different dose recommendations for younger/healthier pts and frailer/older patients 35 36
Treatment Delivery PST will be delivered centrally First session by videocast at a private office in site clinic Future sessions either by telephone, or continuing in videocast Medication sessions conducted by local psychiatrist/primary care provider/advanced care nurse Drugs dispensed and adherence tracked centrally by MEDCO (pending) Assessments Clinical coordinator will be masked to treatment assignment Second clinical coordinator/site PI will inform patient of randomization allocation and educate patient on costs and benefits of choice Assessment data collected on computer and sent to DCC centrally 37 38 Primary Outcome: Patient Satisfaction Safety Protocol Over the last 2 months, how would you rate the quality of care you have received for your depression/distress from your health care providers? Answer options: Excellent, Very good vs poor, fair, good Outcome: % satisfied = % very good or excellent ratings 40
Statistical Considerations With n=150, 80% chance of detecting difference in depression scores between groups of 0.46 SD- units (4 point difference in BDI). Estimation of recruitment yield and retention rates, and variability in event rates will be used to guide definitive trial Comparison of acceptance and adherence rates across sites Comparison of QA metrics of treatment delivery from COPES across sites Thank you 41 42 Additional slides Columbia team William Whang, MD (site PI) Eileen Rattigan, MD Peter Shapiro, MD Vivian M. Medina, Social worker Cynthia Morel (clinical coordinator) Elizabeth Capone-Newtown (clinical coordinator) Gabrielle Albanese Osorio (CODIACs manager) 43 44
Beck Depression Inventory (21 items) #1 I do not feel sad. I feel sad. I am sad all the time and I can t t snap out of it. I am so sad or unhappy that I can t t stand it. #2 I am not particularly discouraged about the future. I feel discouraged about the future. I feel I have nothing to look forward to. I feel that the future is hopeless and that things cannot improve. #16 I can sleep as well as usual. I don t t sleep as well as I used to. I wake up 1-21 2 hours earlier than usual and find it hard to get back to sleep. I wake up several hours earlier than I used to and cannot get back to sleep. 45