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Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy - CREATE
Description:
The goal of the trial was to evaluate interpersonal psychotherapy (IPT) compared with clinical management, and to evaluate the selective serotonin reuptake inhibitor (SSRI) citalopram with placebo in a 2 x 2 factorial design among patients with coronary artery disease (CAD) and major depression.
Study Design
Study Design:
Patients Screened: 1,897
Patients Enrolled: 284
Mean Follow Up: 12 weeks
Mean Patient Age: Mean age 58 years
Female: 25
Patient Populations:
Age ≥18 years; met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a diagnosis of current major depression; depressed for ≥4 weeks; have a baseline score of ≥20 on the centralized, telephone-administered 24-item HAM-D; established CAD based on hospital chart evidence of a previous acute myocardial infarction or cardiac revascularization or coronary angiography showing ≥50% blockage in ≥1 major coronary artery; and stable CAD
Exclusions:
Depression due to a general medical condition; bipolar disorder or major depression with psychotic features; substance abuse or dependency during the previous 12 months; serious suicide risk; current use of antidepressants, lithium, or anticonvulsants for mood disorder; current treatment with any form of psychotherapy; previous absence of response to citalopram or IPT; ≥2 previous unsuccessful treatments for the index depression episode; lifetime history of early termination of citalopram or two other SSRIs because of adverse events; Mini-Mental State Examination score of <24; clinician judgment that the patient would not adhere to the study regimen; discharge from hospital in the prior week; bypass surgery planned during the next 4 months; or Canadian Cardiovascular Society Angina class IV
Primary Endpoints:
Change from baseline to 12 weeks on the HAM-D
Secondary Endpoints:
BDI-II score
Drug/Procedures Used:
Patients were randomized in a parallel, 2 x 2 factorial design to IPT for 12 weeks in addition to clinical management (n = 142) or clinical management only (n = 142). In the other factor, patients were randomized to the SSRI citalopram (20-40 mg/day; n = 142) or placebo (n = 142).
Principal Findings:
At baseline, time since the most recent cardiac event was >2 years in 43% of patients and within 6 months in 27% of patients. Nearly two-thirds of patients had a prior myocardial infarction and 45% had prior bypass surgery. Less than one-third had slight or marked angina limiting ordinary physical activity. Mean Hamilton Depression Rating Scale (HAM-D) score was 30 at baseline. Time since the most recent depression was >2 years in 22% of patients and within 6 months in 37% of patients.
The primary endpoint of reduction in mean HAM-D score was improved in the citalopram group versus placebo (mean reduction 14.9 vs. 11.6, p = 0.005), but did not differ for IPT versus clinical management (mean reduction 12.1 vs. 14.4, p = 0.06).
Likewise, the secondary endpoint of reduction in mean Beck Depression Inventory II (BDI-II) score was improved in the citalopram group versus placebo (mean reduction 14.7 vs. 11.1, p = 0.005), but did not differ for IPT versus clinical management (mean reduction 13.5 vs. 12.4, p = 0.37). Response of ≥50% reduction in HAM-D from baseline was higher in the citalopram group versus placebo (52.8% vs. 40.1%, p = 0.03), as was remission, defined as 12-week HAM-D score of ≤8 (35.9% vs. 22.5%, p = 0.01). Neither blood pressure nor electrocardiographic variables such as mean corrected QT interval differed between the citalopram and placebo groups.
Interpretation:
Among patients with CAD and major depression, treatment with the SSRI citalopram was associated with a larger improvement in depression compared with placebo at 12 weeks. There was no difference in improvement in depression for the comparison of IPT compared with clinical management.
Patients with CAD often have high rates of major depression. Limited randomized trial data exist that focus on therapies for this cohort of patients. The SADHART trial also showed benefit with an SSRI (sertraline) for patients with CAD and major depression. The benefit in both the present study and in SADHART was greater for recurrent episodes of major depression rather than for first episodes.
References:
Lesperance F, Frasure-Smith N, Koszycki D, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007;297:367-79.
Keywords: Myocardial Infarction, Coronary Artery Disease, Depressive Disorder, Major, Serotonin Uptake Inhibitors, Diagnostic and Statistical Manual of Mental Disorders, Blood Pressure, Citalopram, Electrocardiography, Sertraline, Coronary Angiography, Motor Activity, Psychotherapy
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