Celexa Effective Against Depression with Heart Patients

MONTREAL, Jan 23 -- The selective serotonin reuptake inhibitor (SSRI) Celexa (citalopram) appears effective in treating depression among patients with coronary artery disease, researchers here found.

Celexa yielded a 31% greater response rate than placebo, but the addition of interpersonal psychotherapy did not increase the benefit, said Franois Lesprance, M.D., of the University of Montral, and colleagues, in the Jan. 24-31 issue of the Journal of the American Medical Association.

The study adds to the scanty evidence for SSRI use in patients with coronary artery disease and depression, according to an accompanying editorial by Alexander H. Glassman, M.D., and J. Thomas Bigger Jr., M.D., both of Columbia in New York.

The combination of coronary artery disease and depression significantly increases risk of cardiovascular morbidity and mortality, but "there is limited information to guide its treatment and questions have even been raised about whether treatment is needed," they wrote.

One previous trial showed that the SSRI antidepressant Zoloft (sertraline) was effective in this population. However, none, including Dr. Lesprance's study, has shown a corresponding reduction in mortality.

"Although there is suggestive evidence, whether SSRIs reduce cardiac events has not been established," Drs. Glassman and Bigger wrote. "For that a large, randomized clinical trial is urgently needed."

Still, they recommended that "clinicians should screen for depression in patients with coronary heart disease and maintain a low threshold for treatment with an SSRI."

They added that Zoloft and Celexa are the SSRIs least likely to produce drug interactions, which is an important issue because SSRIs have antiplatelet properties.

Tricyclic antidepressants are contraindicated in patients with coronary artery disease and other newer antidepressants have not been extensively evaluated, the editorialists added.

In the study, patients were randomized to Celexa or placebo and psychotherapy or standard medical management visits for 12 weeks. The 284 outpatients randomized to one of the four treatment arms all met DSM-IV criteria for moderate-to-severe major depression as well as stable coronary artery disease.

Celexa and placebo were given at 20 mg/d up to a maximum of 40 mg/d for patients who did not respond. Psychotherapy consisted of 12 visits and addressed interpersonal conflicts, life transitions, grief, loss, and social isolation. Medical management consisted of weekly individual 20- to 25-minute sessions giving information about depression and medication use, reassurance, and encouragement to adhere to medication and the study protocol.

Participants started treatment an average of 18.9 months after their index cardiac hospitalization. The mean age was 58.2 years, 25% were women, and 40.3% to 56.0% had previous depression.

After 12 weeks of treatment, the Celexa groups had a significantly higher remission rate, defined as a score of eight or less on the 24-item Hamilton Depression Rating Scale, compared with placebo groups (51% versus 32%, P=0.01). The difference was not significant between psychotherapy and clinical management (40% versus 43%, P=0.70).

Response, defined as at least a 50% reduction from baseline, was 1.67-fold more common with Celexa compared with placebo (95% CI 1.04 to 2.67). The odds ratio for difference between psychotherapy and clinical management favored clinical management (0.75, 95% CI 0.47 to 1.20).

The baseline demographic, medical, and psychiatric characteristics were balanced between groups except that more women were randomized to clinical management than psychotherapy (P=0.01). However, there were no interactions between therapy or medication and sex.

For the primary outcome of change in the 24-item Hamilton Depression Rating Scale scores from baseline to 12 weeks, the findings were:

• 16.1 point reduction with Celexa plus clinical management,
• 13.7 point reduction with Celexa plus psychotherapy,
• 12.6 point reduction with clinical management plus placebo, and
• 10.5 point reduction with psychotherapy plus placebo.

The difference between Celexa and placebo was significant (difference 3.33, 96.7% confidence interval 0.80 to 5.85, P=0.005) with an effect size of 0.33.

However, clinical management tended to be better than interpersonal psychotherapy (difference -2.26, 96.7% CI -4.78 to 0.27, P=0.06).

Similar trends were seen for the secondary outcome of change in Beck Depression Inventory II scores from baseline to week 12. The findings were:

• 14.1 point reduction with Celexa plus clinical management,
• 15.4 point reduction with Celexa plus psychotherapy,
• 10.7 point reduction with clinical management plus placebo, and
• 11.5 point reduction with psychotherapy plus placebo.

Celexa again came out significantly better than placebo (difference 3.61, 98.3% CI 0.58 to 6.64, P=0.005) with a similar effect size as the primary outcome of 0.33. Again, psychotherapy failed to be better than clinical management (difference 1.13, 98.3% CI -1.90 to 4.16, P=0.37).

The exploratory outcomes for depressive severity, perceived social support, and function in daily activities also supported significant benefit for Celexa over placebo but not for psychotherapy over clinical management.

The lack of benefit from psychotherapy compared with clinical management does not imply that other forms of psychotherapy, particularly cognitive behavioral therapy, are ineffective, the researchers said.

"A less intense control intervention might have revealed some advantage for interpersonal psychotherapy," said Drs. Glassman and Bigger in their editorial.

Interestingly, Celexa appeared to be better than placebo among patients with recurrent depression (mean difference between groups 5.66, 95% CI 2.43 to 8.89) but not among those with a first depression (mean difference 1.08, 95% CI -2.26 to 4.42). This difference in impact may be due to reduced statistical power within that subgroup, the researchers said, though they didn't rule out the possibility of a real effect.

Celexa appeared to be safe for coronary artery disease patients with depression. There were only 12 cardiovascular and 23 noncardiovascular serious adverse events among the 284 patients overall. There were no differences between Celexa and placebo groups in blood pressure or electrocardiographic measures, including QTc intervals.

The events reported more frequently by patients receiving Celexa than placebo were dizziness (48.6% versus 30.3%, P=0.002), diarrhea (49.3% versus 23.9%, P