January 24, 2007 — Citalopram, 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 trial suggest. 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, Fran�ois Lesp�rance, MD, of the University of Montreal, Quebec, Canada, told heartwire. "Contrary to our expectations, psychotherapy did not add anything to the treatment of depression, compared to the control conditions [20 minutes of standard clinical management] in these patients."
Drug Improved Depression
Lesp�rance and colleagues randomized 284 patients with coronary artery disease in a 2 x 2–factorial design to 2 separate randomizations each lasting 12 weeks: 12 weekly sessions of IPT or standard clinical management or 12 weeks of citalopram (20 - 40 mg/day) or matching placebo. The primary endpoint 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 (Sertraline AntiDepressant Heart Attack Trial) and ENRICHD (Enhancing Recovery in Coronary Heart Disease).
After 12 weeks of receiving citalopram, patients had greater reductions in HAM-D scores than did patients taking placebo, with the superiority of drug-treatment apparent within the first 6 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 groups 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," Dr. Lesp�rance told heartwire, adding that the study was also one of the largest studies to also have an appropriate control group.
"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 orientated or exercise-based psychotherapy. The needs of patients with heart disease may be different, and we still need to found a proper psychotherapy treatment."
Cognitive behavior therapy, Dr. Lesp�rance 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," Dr. Lesp�rance 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," Dr. Lesp�rance 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, Alexander H. Glassman, MD, of the New York State Psychiatric Institute, and J. Thomas Bigger, MD, of Columbia University in 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 [acute coronary syndrome] depression can limit the possibility for studies to definitively establish whether SSRIs influence cardiac morbidity and mortality," the editorialists write.
Such a study, however, is "urgently needed," Drs. Glassman and Bigger observe.
JAMA. 2007;297:367-379, 411-412.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
- Compare the benefit of citalopram vs placebo in CAD patients with depression.
- Describe the effect of IPT on depression in CAD patients.
Hospitalized patients with CAD have a prevalence of depression ranging from 17% to 27%. Treating depression may improve CAD prognosis, but there are few well-controlled studies examining the effect of different antidepressant strategies in patients with CAD.
The current study is a 2 x 2–factorial, parallel group, 12-week trial conducted in 284 outpatients with both CAD and depression at 9 academic centers in the United States to compare the effect of citalopram vs placebo and IPT with usual treatment.
- Inclusion criteria were age older than 18 years and meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression of at least 4 weeks with a baseline score of 20 or higher on the 24-item telephone-administered HAM-D.
- Exclusion criteria were depression due to medical condition, bipolar disorder, drug dependency, psychosis, current psychotherapy, or Mini-Mental Status Examination score less than 24.
- Patients had to have established CAD defined as previous acute myocardial infarction (MI) or cardiac revascularization or coronary angiography showing 50% blockage or more in at least 1 coronary artery.
- Patients recruited via advertisement completed baseline BDI-II, the Interpersonal Relationships Inventory (IPRI), 32-item version of the Functional Performance Inventory (FPI), which were repeated at weeks 6 and 12.
- Electrocardiogram, thyroid function test, and HAM-D assessment were completed.
- 284 patients were randomized into 4 groups (n = 67 - 75 patients each): (1) IPT plus clinical management and citalopram, (2) IPT plus clinical management and placebo pill, (3) clinical management only and citalopram, and (4) clinical management only and placebo pill.
- Citalopram was started at 10 mg/day for 1 week, then increased to 20 mg/day. In nonresponders, the dose was increased to 40 mg/day (defined as HAM-D score of > 8 at 6 weeks).
- Clinical management comprised weekly individual 20- to 25-minute sessions providing information about depression, medication use, and encouragement to adhere to treatment.
- IPT consisted of semi-structured psychotherapy that included discussion of personal conflicts, life transitions, grief, and loss.
- IPT was offered by doctoral or master degree level therapists with a mean of 15.8 years experience.
- The HAM-D was administered centrally by telephone at baseline and 6 and 12 weeks by clinical psychologists blinded to assignment.
- Mean age was 58 years, 40% were women, 23% were current smokers, 70% had a history of hypertension, 60% had previous myocardial infarction, 57% had previous coronary angioplasty, and 60% had previous bypass surgery.
- 54 patients discontinued treatment during the study.
- Citalopram was superior to placebo in reducing depressive symptoms in all efficacy measures, and the 12-week HAM-D change in score was 3.3 points for an effect size of 0.33.
- The effect sizes were similar for the BDI-II (0.33) and perceived social support (IPRI, 0.33).
- The effect size for functional performance in daily activities was 0.21.
- The benefits of citalopram were apparent by 6 weeks.
- Adverse effects reported more frequently in the citalopram group were dizziness (49% vs 30%), diarrhea (49% vs 24%), somnolence (44% vs 25%), sweating (39% vs 24%), palpitations (25% vs 15%), and decreased libido (21% vs 7%).
- There was no evidence of superiority for IPT, and remission and response rates did not differ between the IPT and clinical management groups.
- There was no interaction of sex with either the HAM-D or BDI-II score or between sex and medication use.
Pearls for Practice
- Citalopram during 12 weeks of treatment is associated with improved measures of depression in CAD patients with depression.
- IPT for 12 weeks is not associated with improved depression in patients with CAD.