1. Clinical Trial Results. org The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) Trial François Lespérance, MD; Nancy Frasure-Smith, PhD; Diana Koszycki, PhD; Marc-André Laliberté, MD; Louis T. van Zyl, MD; Brian Baker, MBChB; John Robert Swenson, MD; Kayhan Ghatavi, MD; Beth L. Abramson, MD; Paul Dorian, MD; Marie-Claude Guertin, PhD; for the CREATE Investigators Published in JAMA, January 24, 2007 Effects of Citalopram and Interpersonal Psychotherapy on Depression in Patients with Coronary Artery Disease

2. Clinical Trial Results. org CREATE Trial: Background Few randomized controlled trials have evaluated the efficacy of treatments for major depression patients with coronary artery disease (CAD).Few randomized controlled trials have evaluated the efficacy of treatments for major depression patients with coronary artery disease (CAD). No previous studies have simultaneously evaluated an antidepressant and short-term psychotherapy.No previous studies have simultaneously evaluated an antidepressant and short-term psychotherapy. Few randomized controlled trials have evaluated the efficacy of treatments for major depression patients with coronary artery disease (CAD).Few randomized controlled trials have evaluated the efficacy of treatments for major depression patients with coronary artery disease (CAD). No previous studies have simultaneously evaluated an antidepressant and short-term psychotherapy.No previous studies have simultaneously evaluated an antidepressant and short-term psychotherapy. Lespérance et al., JAMA 2007; 297(4): 367-79

3. Clinical Trial Results. org CREATE Trial: Background Cont. CREATE is the first trial specifically designed to evaluate the short-term efficacy and tolerability of 2 depression treatments in patients with CAD: citalopram, a selective serotonin reuptake inhibitor (SSRI), and interpersonal psychotherapy (IPT), a short- term, manual-based psychotherapy focusing on the social context of depression.CREATE is the first trial specifically designed to evaluate the short-term efficacy and tolerability of 2 depression treatments in patients with CAD: citalopram, a selective serotonin reuptake inhibitor (SSRI), and interpersonal psychotherapy (IPT), a short- term, manual-based psychotherapy focusing on the social context of depression. Lespérance et al., JAMA 2007; 297(4): 367-79

4. Clinical Trial Results. org Clinical Management Only n=142 Clinical Management Only n=142 Clinical Management + IPT n=142 Clinical Management + IPT n=142 CREATE 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) > 20 2X2 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) > 20 2X2 Factorial. Randomized. Controlled. Parallel-Group. Double-blinded. Mean age 58.2 years, 25% women  Primary Endpoint Change in 24-item HAM-D from baseline.  Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI- II) score  Primary Endpoint Change in 24-item HAM-D from baseline.  Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI- II) score 12 weeks R R R Citalopram n=75 Placebo n=67 Lespérance et al., JAMA 2007; 297(4): 367-79

5. Clinical Trial Results. org CREATE Trial: Baseline Characteristics Characteristics IPT + Citalopram (n=67) IPT + Placebo (n=75) Clinical Management + Citalopram (n= 75) Clinical Management + Placebo (n=67) Age, mean (SD), yr 58.6 (10.44) 59.4 (9.28) 57.3 (7.83) 57.3 (8.95) Female, n (%) 26 (38.8) 18 (24.0) 7 (9.3) 19 (28.4) Previous MI, n (%) 40 (59.7) 54 (72.0) 49 (65.3) 41 (61.2) HAM-D-24 score, mean (SD) 28.8 (6.39) 30.0 (6.43) 29.6 (6.43) 30.3 (7.64) BDI-II score, mean (SD) 30.2 (8.85) 29.4 (9.83) 30.4 (9.27) 31.3 (9.34) Recurrent Depression, n (%) 33 (49.3) 42 (56.0) 34 (45.3) 27 (40.3) Lespérance et al., JAMA 2007; 297(4): 367-79

6. Clinical Trial Results. org Citalopram was superior in reducing 12-week HAM-D scores (mean difference=3.3 points, p=0.005) vs. placebo.Citalopram was superior in reducing 12-week HAM-D scores (mean difference=3.3 points, p=0.005) vs. placebo. There was no significant difference in mean HAM-D scores for clinical management vs. IPT.There was no significant difference in mean HAM-D scores for clinical management vs. IPT. 24-item HAM-D score (mean) CREATE Trial: Primary Endpoint n = 142 p = 0.005 24-item HAM-D score at follow up for Citalopram vs. Placebo Lespérance et al., JAMA 2007; 297(4): 367-79

7. Clinical Trial Results. org Citalopram was superior in reducing BDI-II scores (mean difference=3.6 points, p=0.005) vs. placebo.Citalopram was superior in reducing BDI-II scores (mean difference=3.6 points, p=0.005) vs. placebo. There was no significant difference in BDI-II scores for clinical management vs. IPT.There was no significant difference in BDI-II scores for clinical management vs. IPT. BDI-II score (mean) CREATE Trial: Secondary Endpoint n = 142 p = 0.005 BDI-II score at follow up for Citalopram vs. Placebo Lespérance et al., JAMA 2007; 297(4): 367-79

8. Clinical Trial Results. org CREATE Trial: Limitations Recruitment of participants through advertisements and exclusion of those unwilling to accept randomization, both of which reduced the generalizability of results.Recruitment of participants through advertisements and exclusion of those unwilling to accept randomization, both of which reduced the generalizability of results. Even though most analyses were preplanned, some significant differences may have occurred by chance.Even though most analyses were preplanned, some significant differences may have occurred by chance. Recruitment of participants through advertisements and exclusion of those unwilling to accept randomization, both of which reduced the generalizability of results.Recruitment of participants through advertisements and exclusion of those unwilling to accept randomization, both of which reduced the generalizability of results. Even though most analyses were preplanned, some significant differences may have occurred by chance.Even though most analyses were preplanned, some significant differences may have occurred by chance. Lespérance et al., JAMA 2007; 297(4): 367-79

9. Clinical Trial Results. org CREATE Trial: Limitations Cont. By chance, more women were randomized to receive IPT than clinical management alone; however, there was no difference between men and women in their responses to citalopram/placebo or IPT/clinical management.By chance, more women were randomized to receive IPT than clinical management alone; however, there was no difference between men and women in their responses to citalopram/placebo or IPT/clinical management. Lespérance et al., JAMA 2007; 297(4): 367-79

10. Clinical Trial Results. org CREATE Trial: Summary CREATE trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for patients with CAD.CREATE trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for patients with CAD. There is, however, no evidence of added value of IPT over clinical management.There is, however, no evidence of added value of IPT over clinical management. CREATE trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for patients with CAD.CREATE trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for patients with CAD. There is, however, no evidence of added value of IPT over clinical management.There is, however, no evidence of added value of IPT over clinical management. Lespérance et al., JAMA 2007; 297(4): 367-79

11. Clinical Trial Results. org CREATE Trial: Summary Based on this trial and previous studies, citalopram or sertraline in addition to clinical management should be considered as a first- step treatment for patients with CAD and major depression.Based on this trial and previous studies, citalopram or sertraline in addition to clinical management should be considered as a first- step treatment for patients with CAD and major depression. Lespérance et al., JAMA 2007; 297(4): 367-79