One of the most critical issues now facing clinicians is how to best treat depressed cardiac patients. Current recommendations for depression treatment typically involve pharmacotherapy, usually with a selective serotonin reuptake inhibitor (SSRI), although treatments with tricyclic antidepressants, benzodiazepines, and combined therapies are also prescribed (5). It has been estimated that approximately 50% of patients will have a clinical “response” to treatment (i.e., a 50% reduction in symptoms), whereas many patients will require augmented treatment with >1 antidepressant agents (6). However, many patients do not respond to antidepressant medications or experience untoward side effects. Indeed, although data are limited, results from several randomized controlled trials of antidepressants in cardiac patients have provided negative or equivocal findings. For example, the SADHART (Sertraline Against Depression and Heart Disease) trial was a randomized, double-blind, placebo-controlled, 24-week trial of sertraline for MDD among patients hospitalized for acute MI (7). Improvement in depressive symptoms among participants treated with sertraline was observed only in a subset of patients with more severe depression; there was no difference between sertraline and placebo in the full sample. The study was not powered to examine clinical outcomes. A second study (SADHART-CHF [Sertraline Against Depression and Heart Disease in Chronic Heart Failure] trial) confirmed the safety of sertraline among patients with chronic heart failure, but sertraline did not reduce depressive symptoms any more than placebo (8). Moreover, participants treated with sertraline had no better clinical outcomes compared with those receiving placebo. The MIND-IT study (Myocardial INfarction and Depression-Intervention Trial) also failed to demonstrate improvement in either depressive symptoms or cardiac outcomes with antidepressant treatment (9). In one of the few positive trials, the CREATE (Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy) study (10) reported that depressive symptoms and remission rates were improved with citalopram compared with placebo, whereas no differences in depressive symptoms were observed between patients receiving interpersonal therapy and clinical management compared with patients receiving clinical management alone. The sample was too small to examine clinical outcomes, however. Meta-analyses of randomized, controlled trials of antidepressant medications in cardiac patients generally have reported no significant differences between antidepressant medication and placebo controls, but the authors still encouraged the use of antidepressant drugs because nonrandomized trials showed greater benefits with medication ((11),12).