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.

CONTEXT: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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). MAIN OUTCOME MEASURES: 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. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN15858091.

Defining guilt in depression: a comparison of subjects with major depression, chronic medical illness and healthy controls.

BACKGROUND: Although guilt is a widely accepted feature of depression, there is limited and inconsistent data defining the nature of this symptom. The purpose of the current study was to examine the specificity and nature of guilt in subjects with major depression as compared to patients with another chronic medical illness and healthy controls. METHODS: Outpatients with current major depressive episode (MDE; n=34), past-MDE (n=22), chronic cardiac illness (n=20) and healthy controls (n=59) were administered the following measures: The Guilt Inventory (GI), State Shame and Guilt Scale (SSGS), 17-item Hamilton Rating Scale for Depression (Ham-D) and the Structured Clinical Interview for DSM-IV. RESULTS: Overall multivariate analysis of covariance comparing mean scores for the six guilt subscales [state-guilt, trait-guilt, moral standards (from the GI); state-guilt, -pride, and -shame (from the SSGS)] across the four groups was significant (F=9.1, df=6:121, p<0.0001). Post-hoc analysis revealed the following differences (each at least p<0.01): for state-guilt (GI), current-MDE>past-MDE>cardiac=healthy controls; for trait-guilt (GI), current-MDE=past-MDE>cardiac=healthy controls; for state-shame, -guilt and -pride (SSGS), current-MDE>past-MDE, past-MDE=cardiac, past-MDE>healthy, cardiac=healthy controls. Among depressed patients, there was significant correlation between Ham-D score and all guilt sub-scales (p<0.01), except moral standards. LIMITATIONS: The cardiac group may have less illness burden than currently depressed. CONCLUSIONS: State expression of guilt, shame and low pride distinguish acutely depressed from all other groups, and are highly influenced by severity of depression. Trait-guilt does not differentiate acute from past depressed. Data suggests guilt may represent both an enduring and fluctuating feature of depressive illness over its longitudinal course.