This use of the IPT therapists for clinical management generated extensive discussion at the meeting. Despite assurances by the investigators that the clinical management sessions were closely monitored, some audience members questioned whether the clinical management-alone arm received more therapy than a nurse practitioner would deliver as usual care to similar patients who were outside of the trial.
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Does Treatment Reduce Deaths?
CREATE was the third large clinical trial to investigate treatment of major depressive disorder in heart disease patients.
In the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART), investigators did not find the selective serotonin reuptake inhibitor sertraline (Zoloft) to be significantly better than placebo in reducing depressive symptoms for the population overall, but it was safe and more effective for recurrent depression in patients with a recent myocardial infarction or unstable angina (JAMA 2002;288:701–9).
In the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial, investigators compared 6 months of cognitive-behavioral therapy supplemented as needed with sertraline with usual care in 2,481 patients who were depressed when enrolled 1 month after an acute myocardial infarction. Changes on the Hamilton Depression Scale were statistically significant, but therapy had no impact on the primary outcomes of the study: death or recurrent myocardial infarction (JAMA 2003;289:3106–16).
The direct effect that lowering cholesterol or relieving depression has on heart disease may never be known, said Dr. Nancy Frasure-Smith, a CREATE investigator, in a plenary lecture before release of the CREATE results at the Academy of Psychosomatic Medicine meeting. Statins and antidepressants have pleiotropic effects, she said; they can affect multiple systems or metabolic processes. With respect to antidepressants, she cited human and animal studies showing impacts on platelet activation, endothelial function, C-reactive protein levels, and inflammation.
“If any of these treatments improves prognosis in coronary artery disease patients, we'll know [it] should be widely used because it helps improve survival,” she said. “But because of the pleiotropic effects of most available depressant treatments, we will not know what the impact is because of a change in depression itself.” Depression should be treated in its own right, she advised, reminding cardiologists about “the compliance issue:” Depressed patients are less likely to adhere to treatment of their coronary artery disease.