In what was billed as the first randomized controlled study to simultaneously evaluate antidepressant therapy and short-term psychotherapy for depressed patients with coronary artery disease (CAD), treatment with an SSRI led to significant improvement, while addition of interpersonal psychotherapy provided no added benefit.
With evidence increasing over 2 decades that major depression worsens the prognosis in patients with CAD, the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial was conducted to examine the safety and efficacy of the 2 treatment strategies for depression in a group of outpatients with CAD.1
The study's lead investigators, Francois Lespérance, MD, and Nancy Frasure-Smith, PhD, both from the department of psychiatry, University of Montreal, argued that although there is not yet clear evidence that effective treatment of depression can reduce the morbidity and mortality of CAD, the "available data are more than sufficient to justify developing and evaluating better treatments for depression in patients [with CAD] as well as in those at risk for its development."2
The largest previous investigation of depression treatment in CAD was the Sertraline Antidepressant Heart Attack Trial (SADHART),3 which, according to the CREATE investigators, provided some evidence of the safety of the SSRI sertraline (Zoloft) in patients with CAD. The CREATE investigators note, however, that the "overall efficacy results were less convincing."1
The CREATE trial also used an SSRI (citalopram [Celexa]), chosen because of its relatively low propensity to adversely interact with cardiac medications and the absence of noradrenergic or anticholinergic activity (which can affect cardiac function) that is characteristic of an SSRI. The CREATE trial differed from SADHART by including a psychotherapeutic intervention and widening the study population beyond those hospitalized with acute coronary syndrome. Their inclusion criteria, the CREATE investigators indicated, "help ensure the applicability of results to a wide group of cardiac patients."1
The CREATE investigators identified 284 patients at 9 Canadian academic medical centers who were at least 1 week post-myocardial infarction (MI), cardiac revascularization, or coronary angiography with substantial blockage, and had at least 4 weeks of depressive symptoms rated 20 or higher on the 24-item Hamilton Depression Rating Scale (HAM-D). The patients were randomized into 4 groups, to receive: (1) 12 weekly sessions of interpersonal therapy (IPT) plus clinical management and citalopram; (2) 12 weeks of IPT plus clinical management and placebo pill; (3) clinical management and citalopram; or (4) clinical management and placebo pill.
Citalopram was initiated at 10 mg daily for the first week, then increased to 20 mg. If the HAM-D score was not 8 or lower by the 6th week, the dosage was increased to 40 mg daily and maintained, if tolerated, through the remaining 6 weeks. The clinical management protocol, previously used in the NIMH Treatment of Depression Collaborative Research Program,4 involved weekly 20- to 25-minute sessions along with monitoring of both mood and physical symptoms.
IPT was chosen over cognitive- behavioral therapy (CBT)—the only other psychotherapeutic intervention recommended in depression treatment guidelines—in part because of a previous study finding it superior to CBT for treating depression in patients with comorbid medical illness.5
"Interpersonal psychotherapy deals with problems common in patients with CAD, including interpersonal conflicts, life transitions, grief, and loss," the CREATE investigators explained. "It also addresses social isolation, a factor that has been linked to increased mortality and morbidity in some studies of patients with CAD."1
1. Lespérance 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;297:367-379.
2. Frasure-Smith N, Lespérance F. Reflections on depression as a cardiac risk factor. Psychosom Med. 2005; 67:S19-S25.
3. Glassman AH, O'Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-709.
4. Fawcett J, Epstein P, Fiester SJ, et al. Clinical management-imipramine/placebo administration manual. NIMH Treatment of Depression Collaborative Research Program. Psychopharmacol Bull. 1987;23:309-324.
5. Markowitz JC, Kocsis JH, Fishman B, et al. Treatment of depressive symptoms in human immunodeficiency virus-positive patients. Arch Gen Psychiatry. 1998;55: 452-457.
6. Frasure-Smith N, Lespérance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA. 1993;270:1819-1825.
7. Berkman LF, Blumenthal J, Burg M, et al, and the Enhancing Recovery in Coronary Heart Disease Patients Investigators. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA. 2003;289:3106-3116.
8. Frasure-Smith N, Lespérance F. Depression—a cardiac risk factor in search of a treatment. JAMA. 2003; 289:3171-3173.