1

Comparison of Depression Interventions after Acute Coronary

Syndrome

Funded by the National Heart Lung and Blood InstituteRC2-HL-101663

Depressive Symptoms are Related to Acute Coronary Syndromes

• Increased risk of ACS recurrence/mortality• Independent of traditional risk factors• Reduced long-term survival (up to 5-years) post ACS• Dose-dependent• Highly prevalent

• 35-45 % of with elevated depressive symptom• Risk occurs at a relatively low level of depressive

symptoms (Beck Depression inventory I score of > 10)

2

Adjusted Depressive Symptoms in CHD Patients and All-cause Mortality

Barth J, Shumacher M., & Herrmann-Lingen H. Psychosomatic Medicine, 2004 3

Post-MI Depressive Symptoms and Cardiac Mortality

vanMelle et al., Psychosomatic Medicine 2004

4

4003002001000

100%

95%

90%

85%

80%

BDI < 10

BDI > 10

Odds Ratio = 4.7 (1.9 – 11.3)

P< 0.001

Lespérance et al., 2000

N=430

Sur

viva

l Fre

e of

Car

diac

Mor

talit

y or

Non

-F

atal

MI,

Cum

ulat

ive

%

Time After for Unstable Angina, Discharge Days

Patients with Unstable Angina

5

6

BDI < 4

BDI 4 to 9

BDI 10 to 18

BDI > 19

Time after discharge for MI, days

N=896

Lesperance et al. Circulation. 2002

Long-term Survival Impact of Increasing Levels of Post-MI

Depression (BDI Score) S

urvi

val F

ree

of C

ardi

ac M

orta

lity,

C

umul

ativ

e %

7

Current depression/depressive symptoms

Depression Conceptualizations

Assess current depression/depressive symptoms

Acute coronary disease event

time

MACE/ACM risk

Depressive Symptoms and 42-month MACE/ACM

Strata —— Low Depressive symptoms——High Depressive symptoms

8

Persistent depressive symptoms

Depression Conceptualizations

Assess current depression/depressive symptoms

Acute coronary disease event

time

MACE/ACM risk

9

10

Persistent Depression and 42-month MACE/ACM

Strata — Non Depressed——Remitted Depressed——Persistent Depressed

Would you rather take medication or get counseling?

0

10

20

30

40

50

60

70

80

90

100

BDI 0-4 BDI 10-16 BDI >16

40

55 5460

43

50Take Medications

Go to counseling

11

Note: sometimes people check both options, thus total is > 100%

Per

cen

tag

e A

gree

ing

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

• Medical patients are have strong preferences for, and against, both psychotherapy and medication to treat their depressive symptoms

12

To explore in a depression intervention RCT the patient satisfaction and depressive symptom reduction of a patient-preference, stepped-care model (problem-solving therapy 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-25197

13

COPES 2 RCT Aims

14

Percent Rating

Depression Care as…

UC

(n=77)

INT

(n=80)

OR

(95% CI)P

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

Percent receiving no care at 3 mo 73.7% 71.6% … …

Percent receiving no care at 9 mo 62.3% 27.1% … …

COPES Satisfaction with Care (Primary Outcome)

Satisfaction with Depression Care

Usual care (18%) vs.

Intervention (54%)

15

16

Variable UC

(n=77)

INT

(n=80)

INT vs UCNon-depressed

(n=80)Between-Group

Difference P

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)

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)

Beck Depression Group Differences

Effect size .59

Beck Depression Group Differences

17

Average Difference Between Groups on the Beck Depression Inventory

at Treatment End

ACREATE data for comparison between IPT (Intervention) and Clinical Management (Control) BCREATE data for comparison between Citalopram (Intervention) and Placebo (Control)

BDI-II{

18

Days to Major Adverse Coronary Event/Death by Group Status

• 4% Intervention and 13% Usual care; log-rank test

• χ2(1)=3.78; P=.048; 5 nondepressed patients had MACE (6%)

19

• To determine the feasibility and effectiveness of the COPES intervention for depression in post-ACS patients at other sites

• To obtain estimates of yield, satisfaction, and retention for use in planning a large phase 3 clinical trial

Funded by the National Heart Lung and Blood InstituteRC2-HL-101663

20

CODIACS Aims

21

• 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

CODIACS Design

22

CODIACS Organizational Chart

23

• Satisfaction with depression care

• Depression scores (BDI)

CODIACS Endpoints

CODIACS InclusionCriteria

• Hospitalized for acute coronary syndrome (ACS) in previous 2-4 months

• Beck Depression Inventory (BDI) score >10 and <15 on each of 2 occasions (1-2 weeks apart), or BDI>15 on one occasion

• Age >18 years

24

CODIACS Exclusions

• Inability to complete the baseline assessment within 2-4 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 illness25

26

CODIACS CONSORT

27

CODIACS 2009 Timeline

October• Grant awarded• #1 SC meeting

November• IRB submission• #2 SC meeting• Forms finalized

December• DSMB protocol review• IRB approved or modified, if needed

28

CODIACS 2010 TimelineJanuary• Staff training• Screening begins• First patient randomized CUMCFebruary• DMS training• #3 SC meetingMarch• Event Adjudication Committee training• All sites randomizingMay• Preparation of design manuscriptJuly• #4 SC meeting• First patient completes follow-up

29

CODIACS 2010 Timeline

August• Design manuscript submission• #1 DSMB meetingOctober• IRB renewal submittedNovember• #1 Event Adjudication Meeting• #5 SC meetingDecember• Core status reports• Forms, protocol, and MCPs completed

for Phase III trial• Last patient randomized

30

CODIACS 2011 TimelineJanuary• Review of Milestones and Deliverables• Last patient randomized• #2 DSMB meetingMarch• Interim data analysis of yield, acceptance, retention

estimatesApril• #2 Event Adjudication Meeting• #7 SC in-person meeting to outline R01s, cores,

and finalize budget• NHLBI over $500k letter submittedMay• Preparation of design manuscript

31

CODIACS 2011 Timeline

June• Phase III trial R01 submittedJuly• Last patient completes intervention• Final data cleaningAugust• Primary Manuscript preparationSeptember• Primary Manuscript submission

32

CODIACS 2011 Timeline

June• Phase III trial R01 submittedJuly• Last patient completes intervention• Final data cleaningAugust• Primary Manuscript preparationSeptember• Primary Manuscript submission

    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,

consent, BDI

Satisfaction with care,

BDIBDI BDI 

Satisfaction with care,

BDI 

Assessment Schedule

33

Patient choice

Insufficient response options:• Augment with first line antidepressant• Switch to first line antidepressant• Switch to different antidepressant type

Insufficient response options:• Augment with PST• Switch to different antidepressant type

Problem solving therapy (PST)Antidepressant (usually sertraline)

Full response: MaintenanceFull response: Maintenance

Insufficient response options:• Augment with other antidepressant• Referral for Cognitive Behavioral

therapy

Insufficient response options:• Augment with PST• Augment with other antidepressant• Referral for Cognitive Behavioral therapy

Full response: Maintenance / Relapse preventionFull response: Maintenance / Relapse

prevention

Step 1

Step 2

Step 3

6-8 weeks

6-8 weeks

34

CODIACS

Decision Rules for Increasing, Augmenting or Switching Treatment

35

PHQ9 Score remain

5-10

11-20

> 20

Needed Improvement to

at Treatment Choice

30% (score of 4-7)

50% (score of 6-10)

60% (score of 8-11)

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

36

Successful Treatment

37

• Patient’s primary care provider informed in writing of elevated depressive symptoms

• Provider offers usual care treatment

• We follow for type of treatment offered

Referred Care

38

• Patient educated about the costs and benefits of choosing anti-depressant or psychotherapy or both

• Patient chooses first step

• Every 6-8 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

Stepped Care

39

• Brief form of psychotherapy that teaches people how to solve the problems that contributed to depression

• Collaborative care model: depression care specialist, primary care provider, patient

• Treatment duration: 4-8 sessions, total treatment time 2.5-4.5 hours

• Will be conducted by telephone if convenient for patient

Problem Solving Treatment

• Provider choice of Sertraline or citalopam

• Bupropion only used if (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

40

Medication Options

• PST will be delivered centrally

• First session by videocast at a private office in site clinic

• Subsequent sessions either by telephone, or continue with videocasts

• Medication sessions conducted by local psychiatrist/primary care provider/advanced care nurse

• Drugs dispensed and adherence tracked centrally by MEDCO (pending)

41

Treatment Delivery

• 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

• Data collected on computer and sent to DCC centrally

42

Assessments

“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

43

Primary Outcome: Patient Satisfaction

44

Safety Protocol

45

• 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 will be used to guide definitive trial

• Comparison across sites of satisfaction with care, therapy adherence rates, and event rates

• Comparison across sites of QA metrics of treatment delivery

Statistical Considerations

46

Thank you

47

Columbia University team

William Whang, MD (Site PI)Eileen Rattigan, MDPeter Shapiro, MD

Vivian M. Medina, Social WorkerCynthia Morel (Clinical Coordinator)

Elizabeth Capone-Newtown (Clinical Coordinator)Gabrielle Albanese Osorio (CODIACs Manager)

48

#1• I do not feel sad• I feel sad• I am sad all the time and I can’t snap out of it• I am so sad or unhappy that I can’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 sleep as well as I used to• I wake up 1-2 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

Beck DepressionInventory (21 items)