Lessons from SADHART, ENRICHD, and other trials.

Depression is highly prevalent in patients with cardiovascular disease and is independently associated with a poor prognosis when present. A very important aspect of continued therapeutic advances in this field will be the ability to show a convincing connection between the treatment of depression in patients with heart disease and a reduction in morbidity and mortality associated with the co-occurrence of these conditions. The recent SADHART (Sertraline AntiDepressant Heart Attack Trial) investigation demonstrated that sertraline is safe and efficacious in depressed patients with ischemic heart disease but was underpowered to detect a mortality difference between sertraline and placebo. The ENRICHD (ENhancing Recovery in Coronary Heart Disease) trial showed that cognitive-behavioral therapy is effective for treating depression but had no impact on cardiovascular morbidity or mortality. There are a number of methodologic complexities associated with research regarding depression and cardiovascular disease, including difficulties in the definition and measurement of depression, complexities in the conduction of large-scale trials, ethical considerations surrounding the use of placebo, and interpretation of trial results. In addition, the lack of certainty regarding the pathophysiologic link between depression and cardiovascular disease means that there is a lack of pharmacotherapy targeted specifically at the dysregulated physiology that might explain the increased morbidity and mortality seen when these two conditions occur together.