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The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE)

Trial

The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE)

Trial

FranFranççois Lespois Lespéérance, MD; Nancy Frasure-Smith, PhD; rance, MD; Nancy Frasure-Smith, PhD; Diana Koszycki, PhD; Marc-AndrDiana Koszycki, PhD; Marc-Andréé Lalibert Lalibertéé, MD; Louis T. van Zyl, MD; , MD; Louis T. van Zyl, MD; Brian Baker, MBChB; John Robert Swenson, MD; Kayhan Ghatavi, MD; Brian Baker, MBChB; John Robert Swenson, MD; Kayhan Ghatavi, MD;

Beth L. Abramson, MD; Paul Dorian, MD; Marie-Claude Guertin, PhD; Beth L. Abramson, MD; Paul Dorian, MD; Marie-Claude Guertin, PhD; for the CREATE Investigatorsfor the CREATE Investigators

Published in JAMA,Published in JAMA,

January 24, 2007January 24, 2007

Effects of Citalopram and Interpersonal Psychotherapy on Depression in Patients with Coronary Artery DiseaseEffects of Citalopram and Interpersonal Psychotherapy on Depression in Patients with Coronary Artery Disease


CREATE Trial: BackgroundCREATE Trial: Background

• Few randomized controlled trials have Few randomized controlled trials have evaluated the efficacy of treatments for evaluated the efficacy of treatments for major depression patients with coronary major depression patients with coronary artery disease (CAD).artery disease (CAD).

• No previous studies have simultaneously No previous studies have simultaneously evaluated an antidepressant and short-term evaluated an antidepressant and short-term psychotherapy.psychotherapy.

• Few randomized controlled trials have Few randomized controlled trials have evaluated the efficacy of treatments for evaluated the efficacy of treatments for major depression patients with coronary major depression patients with coronary artery disease (CAD).artery disease (CAD).

• No previous studies have simultaneously No previous studies have simultaneously evaluated an antidepressant and short-term evaluated an antidepressant and short-term psychotherapy.psychotherapy.

Lespérance et al., JAMA 2007; 297(4): 367-79Lespérance et al., JAMA 2007; 297(4): 367-79


CREATE Trial: Background Cont.CREATE Trial: Background Cont.

• CREATE is the first trial specifically CREATE is the first trial specifically designed to evaluate the short-term efficacy designed to evaluate the short-term efficacy and tolerability of 2 depression treatments in and tolerability of 2 depression treatments in patients with CAD: citalopram, a selective patients with CAD: citalopram, a selective serotonin reuptake inhibitor (SSRI), and serotonin reuptake inhibitor (SSRI), and interpersonal psychotherapy (IPT), a short-interpersonal psychotherapy (IPT), a short-term, manual-based psychotherapy focusing term, manual-based psychotherapy focusing on the social context of depression.on the social context of depression.

• CREATE is the first trial specifically CREATE is the first trial specifically designed to evaluate the short-term efficacy designed to evaluate the short-term efficacy and tolerability of 2 depression treatments in and tolerability of 2 depression treatments in patients with CAD: citalopram, a selective patients with CAD: citalopram, a selective serotonin reuptake inhibitor (SSRI), and serotonin reuptake inhibitor (SSRI), and interpersonal psychotherapy (IPT), a short-interpersonal psychotherapy (IPT), a short-term, manual-based psychotherapy focusing term, manual-based psychotherapy focusing on the social context of depression.on the social context of depression.



Clinical Management Only

n=142

Clinical Management Only

n=142

Clinical Management + IPT

n=142

Clinical Management + IPT

n=142

CREATE Trial: Study DesignCREATE Trial: Study Design

Citalopram

n=67

Placebo

n=75

284 Patients with CAD from 9 Canadian academic centers, meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression > 4

weeks duration and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) > 202X2 Factorial. Randomized. Controlled. Parallel-Group. Double-blinded.

Mean age 58.2 years, 25% women

284 Patients with CAD from 9 Canadian academic centers, meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression > 4

weeks duration and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) > 202X2 Factorial. Randomized. Controlled. Parallel-Group. Double-blinded.

Mean age 58.2 years, 25% women

Primary Endpoint Change in 24-item HAM-D from baseline.Primary Endpoint Change in 24-item HAM-D from baseline. Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI-Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI-

II) scoreII) score

Primary Endpoint Change in 24-item HAM-D from baseline.Primary Endpoint Change in 24-item HAM-D from baseline. Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI-Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI-

II) scoreII) score

12 weeks 12 weeks

RR

RR RR

Citalopram

n=75

Placebo

n=67



CREATE Trial: Baseline CharacteristicsCREATE Trial: Baseline Characteristics

CharacteristicsCharacteristics IPT + IPT + CitalopramCitalopram

(n=67)(n=67)

IPT + IPT + PlaceboPlacebo(n=75)(n=75)

Clinical Clinical Management + Management +

Citalopram Citalopram (n= 75)(n= 75)

Clinical Clinical Management + Management +

PlaceboPlacebo(n=67)(n=67)

Age, mean (SD), yrAge, mean (SD), yr 58.6 (10.44)58.6 (10.44) 59.4 (9.28)59.4 (9.28) 57.3 (7.83)57.3 (7.83) 57.3 (8.95)57.3 (8.95)

Female, n (%)Female, n (%) 26 (38.8)26 (38.8) 18 (24.0)18 (24.0) 7 (9.3)7 (9.3) 19 (28.4)19 (28.4)

Previous MI, n (%)Previous MI, n (%) 40 (59.7)40 (59.7) 54 (72.0)54 (72.0) 49 (65.3)49 (65.3) 41 (61.2)41 (61.2)

HAM-D-24 score, HAM-D-24 score, mean (SD)mean (SD)

28.8 (6.39)28.8 (6.39) 30.0 (6.43)30.0 (6.43) 29.6 (6.43)29.6 (6.43) 30.3 (7.64)30.3 (7.64)

BDI-II score, mean BDI-II score, mean (SD)(SD)

30.2 (8.85)30.2 (8.85) 29.4 (9.83)29.4 (9.83) 30.4 (9.27)30.4 (9.27) 31.3 (9.34)31.3 (9.34)

Recurrent Recurrent Depression, n (%)Depression, n (%)

33 (49.3)33 (49.3) 42 (56.0)42 (56.0) 34 (45.3)34 (45.3) 27 (40.3)27 (40.3)



14.9

11.6

0

5

10

15

Citalopram Placebo

14.9

11.6

0

5

10

15

Citalopram Placebo

• Citalopram was Citalopram was superior in reducing superior in reducing 12-week HAM-D 12-week HAM-D scores (mean scores (mean difference=3.3 points, difference=3.3 points, p=0.005) vs. placebo.p=0.005) vs. placebo.

• There was no There was no significant difference significant difference in mean HAM-D in mean HAM-D scores for clinical scores for clinical management vs. IPT.management vs. IPT.

24-it

em H

AM

-D s

core

(m

ean)

24-it

em H

AM

-D s

core

(m

ean)

CREATE Trial: Primary EndpointCREATE Trial: Primary Endpoint

n = 142n = 142 n = 142n = 142

p = 0.005p = 0.005

24-item HAM-D score at follow up for Citalopram vs. Placebo24-item HAM-D score at follow up for Citalopram vs. Placebo



14.7

11.1

0

5

10

15

Citalopram Placebo

14.7

11.1

0

5

10

15

Citalopram Placebo

• Citalopram was Citalopram was superior in reducing superior in reducing BDI-II scores (mean BDI-II scores (mean difference=3.6 points, difference=3.6 points, p=0.005) vs. placebo.p=0.005) vs. placebo.

• There was no There was no significant difference significant difference in BDI-II scores for in BDI-II scores for clinical management clinical management vs. IPT.vs. IPT.

BD

I-II

sco

re (

mea

n)B

DI-

II s

core

(m

ean)

CREATE Trial: Secondary EndpointCREATE Trial: Secondary Endpoint

n = 142n = 142 n = 142n = 142

p = 0.005p = 0.005

BDI-II score at follow up for Citalopram vs. PlaceboBDI-II score at follow up for Citalopram vs. Placebo



CREATE Trial: LimitationsCREATE Trial: Limitations

• Recruitment of participants through Recruitment of participants through advertisements and exclusion of those advertisements and exclusion of those unwilling to accept randomization, both of unwilling to accept randomization, both of which reduced the generalizability of results.which reduced the generalizability of results.

• Even though most analyses were Even though most analyses were preplanned, some significant differences preplanned, some significant differences may have occurred by chance.may have occurred by chance.

• Recruitment of participants through Recruitment of participants through advertisements and exclusion of those advertisements and exclusion of those unwilling to accept randomization, both of unwilling to accept randomization, both of which reduced the generalizability of results.which reduced the generalizability of results.

• Even though most analyses were Even though most analyses were preplanned, some significant differences preplanned, some significant differences may have occurred by chance.may have occurred by chance.



CREATE Trial: Limitations Cont.CREATE Trial: Limitations Cont.

• By chance, more women were randomized By chance, more women were randomized to receive IPT than clinical management to receive IPT than clinical management alone; however, there was no difference alone; however, there was no difference between men and women in their responses between men and women in their responses to citalopram/placebo or IPT/clinical to citalopram/placebo or IPT/clinical management.management.

• By chance, more women were randomized By chance, more women were randomized to receive IPT than clinical management to receive IPT than clinical management alone; however, there was no difference alone; however, there was no difference between men and women in their responses between men and women in their responses to citalopram/placebo or IPT/clinical to citalopram/placebo or IPT/clinical management.management.



CREATE Trial: SummaryCREATE Trial: Summary

• CREATE trial documents the efficacy of CREATE trial documents the efficacy of citalopram administered in conjunction with citalopram administered in conjunction with weekly clinical management for patients with weekly clinical management for patients with CAD.CAD.

• There is, however, no evidence of added There is, however, no evidence of added value of IPT over clinical management.value of IPT over clinical management.

• CREATE trial documents the efficacy of CREATE trial documents the efficacy of citalopram administered in conjunction with citalopram administered in conjunction with weekly clinical management for patients with weekly clinical management for patients with CAD.CAD.

• There is, however, no evidence of added There is, however, no evidence of added value of IPT over clinical management.value of IPT over clinical management.



CREATE Trial: SummaryCREATE Trial: Summary

• Based on this trial and previous studies, Based on this trial and previous studies, citalopram or sertraline in addition to clinical citalopram or sertraline in addition to clinical management should be considered as a first-management should be considered as a first-step treatment for patients with CAD and step treatment for patients with CAD and major depression.major depression.

• Based on this trial and previous studies, Based on this trial and previous studies, citalopram or sertraline in addition to clinical citalopram or sertraline in addition to clinical management should be considered as a first-management should be considered as a first-step treatment for patients with CAD and step treatment for patients with CAD and major depression.major depression.


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