Montreal, QC - Citalopram (Celexa, Forest Pharmaceuticals), a selective serotonin-reuptake inhibitor (SSRI), is better than placebo in treating heart-disease patients with depression, results of the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial suggest [1]. By contrast, interpersonal psychotherapy (IPT) was no better than standard clinical management in these patients.

"The major new finding is that patients with coronary artery disease improve, on average, as much as other patients with depression and that citalopram works in these patients," lead author Dr François Lespérance (University of Montreal, QC) told heartwire. "Contrary to our expectations, psychotherapy did not add anything to the treatment of depression, compared with the control conditions [20 minutes of standard clinical management] in these patients."

The study is published in the January 24, 2007 issue of the Journal of the American Medical Association.

Lespérance and colleagues randomized 284 patients with coronary artery disease in a 2x2 factorial design to two separate randomizations, each lasting 12 weeks: 12 weekly sessions of IPT or standard clinical management, and 12 weeks of citalopram (20 to 40 mg/day) or matching placebo. The primary end point was change from baseline in the 24-item Hamilton Depression Rating Scale (HAM-D). All patients had a score of 20 or higher at baseline and thus represented a cohort of more severely depressed patients than were studied in previous trials of depression and heart disease, SADHART and ENRICHD.

After 12 weeks on citalopram, patients had greater reductions in HAM-D scores than did patients taking placebo, with the superiority of drug treatment apparent within the first six weeks. Other measures of depression, including the Beck Depression Inventory II (BDI-II) score and perceived social support also favored citalopram. By contrast, in the nonmedical arms of the study, patients improved in response to both IPT and clinical management.

"The psychotherapy we used has been shown to be effective in patients with major depression but without heart disease and has been used in patients with HIV and other comorbid medical conditions and in elderly patients," Lespérance told heartwire, adding that the study was one of the largest studies to also have an appropriate control arm. "This suggests that there is something unique to heart disease. It may be that we need less of an insightful type, or 'talking' type, of psychotherapy and more a problem-solving-oriented or exercise-based psychotherapy. The needs of patients with heart disease may be different, and we still need to find a proper psychotherapy treatment."

Cognitive behavior therapy, he noted, may be a more appropriate approach in this group.

"The bottom line is, treatment of depression requires someone to closely follow up patients and treat them with an antidepressant that has a low risk of drug-drug interactions," Lespérance summarized to heartwire.

Not yet clear is whether the improvement in depressive symptoms in heart-disease patients would also translate into reduced cardiac morbidity and mortality in this group, something several trials have tried—and failed—to demonstrate.

"It will be important to do a major trial to try to improve cardiac outcomes. We have no way of knowing whether [citalopram] will be effective without testing it," Lespérance said. He also pointed out that such a trial would likely need to rely heavily on public funding, since most of the drugs researchers would want to use in such a study are soon to be off patent, and drug companies would have little interest in funding a cardiovascular-outcomes trial at this point.

In an accompanying editorial [2], Drs Alexander H Glassman (New York State Psychiatric Institute, New York) and J Thomas Bigger (Columbia University, New York) point to another stumbling block in the quest to understand the role of antidepressant drugs in preventing cardiac events. "Ironically, the compelling rationale for treating post-ACS depression can limit the possibility for studies to definitively establish whether SSRIs influence cardiac morbidity and mortality," they write.

Such a study, however, is "urgently needed," Glassman and Bigger observe.