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.
BACKGROUND
Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy.


OBJECTIVE
To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression.


METHODS
The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 x 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher.


METHODS
Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142).


METHODS
The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .017).


RESULTS
Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (-2.26 points; 96.7% CI, -4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, -1.90 to 4.16; P = .37; effect size = 0.11).


CONCLUSIONS
This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression.


BACKGROUND
isrctn.org Identifier: ISRCTN15858091.
Lespérance
François
F
Department of Psychiatry, Université de Montréal, Montreal, Quebec, Canada. francois.lesperance@umontreal.ca
Frasure-Smith
Nancy
N
Koszycki
Diana
D
Laliberté
Marc-André
MA
van Zyl
Louis T
LT
Baker
Brian
B
Swenson
John Robert
JR
Ghatavi
Kayhan
K
Abramson
Beth L
BL
Dorian
Paul
P
Guertin
Marie-Claude
MC
D000368:Aged; D015283:Citalopram / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000150:complications / Q000523:psychology*; D003865:Major Depressive Disorder / Q000150:complications / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011614:Psychotherapy, Brief; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors