Antidepressant-induced cardioprotection after event reverses with a vengeance — (Internal Medicine News)

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American College of Cardiology 2013



SAN FRANCISCO – If ever a study drove home the point that depression – including post–acute coronary syndrome depression – is a chronic relapsing disorder requiring long-term maintenance therapy, it’s the COPES trial.

COPES (Collaborative Psychosocial Evaluation Studies) was a randomized, prospective, single-blind trial in which patients with persistent depressive symptoms after an ACS event received 6 months of enhanced, centralized antidepressant therapy or usual care. Six months post randomization, the intervention group showed significantly lower depression scores than controls did, together with an accompanying impressive reduction in the combined endpoint of death, myocardial infarction (MI), or unstable angina.

Dr. Siqin Ye

That’s the good news. The COPES message that effective antidepressant therapy appears to reduce the risk of recurrent cardiac events has met with a warm reception.

Now the bad news: A just-completed 2-year follow-up of COPES participants showed that the cardioprotective benefit didn’t persist.  Between 6 months and 2 years, a catch-up phenomenon occurred, such that at the 2-year mark the cumulative cardiac event rate in the intervention and usual-care arms was essentially the same, Dr. Siqin Ye reported at the annual meeting of the American College of Cardiology.

“Depression is a relapsing, remitting chronic illness, and the effect of brief enhanced depression therapy after ACS may diminish over time. In future studies we’re going to need to examine how the benefits of short-term depression therapy can be sustained long-term in post-ACS patients with depression,” said Dr. Ye, a cardiologist at the Center for Behavioral Cardiovascular Health of Columbia University Medical Center, New York.

That should not be difficult to accomplish, he explained in an interview. The main form of antidepressant therapy utilized in COPES, known as problem-solving therapy, can be delivered over the phone or on the Internet, making it amenable to ongoing, periodic, low-cost maintenance therapy sessions.

COPES included 157 patients with persistent depressive symptoms after an ACS event as defined by a Beck Depression Inventory score of 10 or more both during their initial hospitalization and 3 months later. They were randomized to enhanced depression therapy involving their choice of problem-solving therapy and/or antidepressant medication using a stepped-care approach with reevaluation and adjustments every 8 weeks, or to usual care. The primary care physicians and cardiologists of patients in the usual-care group received a letter from the investigators informing them that their patient had elevated depressive symptoms.

Three-quarters of patients in the intervention group opted for problem-solving therapy, 20% chose medication, and the rest picked dual therapy. Once the 6-month intervention ended, there were no more problem-solving therapy sessions, and continuation of antidepressant medications was left up to the patient’s own physicians.

Problem-solving therapy is a brief, protocol-driven therapy in which patients are taught how to evaluate and address their psychosocial problems. It was originally developed for use in the IMPACT (Improving Mood-Promoting Access to Collaborative Treatment) trial (JAMA 2002;288:2836-45). In COPES, patients had weekly individual sessions with a psychiatrist or other mental health professional trained in problem-solving therapy that lasted 30-45 minutes.

During the 6-month intervention, 3 major cardiac events occurred in the intervention group, compared with 11 in the usual-care arm. However, between 6 months and 2 years, there were 2 deaths and 9 hospitalizations for acute MI or unstable angina in the original intervention group, compared with 1 death and 2 hospitalizations among controls. Thus, the 2-year total was 14 events in each group.

Stated another way, the risk of a major cardiac event in the enhanced depression therapy group was 77% lower than in the usual-care group during the 6 months of the intervention, but afterward it was 3.4-fold higher than in the usual-care group, according to Dr. Ye.

The COPES trial was funded by the National Heart, Lung, and Blood Institute. Dr. Ye reported having no financial conflicts.