Treatment of Mood Disorders - Specific Medical Illnesses

Treatment of Mood Disorders: Specific Medical Illnesses

Cardiovascular Disease

Exciting progress has been made involving the relationship of coronary artery disease (CAD) and depression. Among patients with CAD, the prevalence of major depression has been shown to be at least threefold higher than that of noncardiac patients. Numerous studies have consistently demonstrated a significant difference in cardiac events and mortality, despite evidence that depression does not increase the severity of the anatomic disease. Approximately 20%-40% of patients with CAD have been shown to have depressive symptoms, and in this group of patients, the mortality rate 6 months after MI was five times higher than that of nondepressed patients with CAD. Further study revealed that 30% of patients with depressive symptoms (with or without meeting criteria for major depression) had a higher mortality rate over 18 months of follow-up. This difference in mortality rate remained an independent variable even when controlling for decreased left ventricular ejection fraction and previous MI (adjusted hazard ratio 4.29). Barefoot et al. (1989) showed that depressed patients with CAD had a risk of sudden cardiac death 84% higher than nondepressed patients with CAD. The data clearly demonstrate the significant role that depression plays in CAD, but the mechanism of this contribution is still based on theory. It is known that depression leads to the dysregulation of the sympathetic nervous system and of the HPA axis. These changes have been found to result in elevations in plasma and urinary cortisol, catecholamines, and their metabolites. Not surprisingly, these neuroendocrine changes have been implicated in the evolution of coronary disease. Platelet aggregation has also been found to be altered in patients with depressive illness. With increased platelet reactivity and aggregation, the myocardial ischemic threshold may be lowered and potentially increase anginal symptoms. This increase in platelet aggregation could also lead to increased thrombus formation and increased risk for infarction. Studies are currently under way to determine how the biochemical changes that occur with depression contribute to the pathogenesis of CAD.

From a biochemical and physiological standpoint, much of this information is internally consistent. Increased platelet activation and exaggerated platelet reactivity have been found in unmedicated patients with major depressive illness. Circulating platelet factor 4 and β-thromboglobulin, markers of platelet activation, are lower in nondepressed patients without ischemic heart disease than in nondepressed patients with ischemic heart disease. These markers are also found at much higher levels in patients who are both depressed and have depressive disorders. Depression has been associated with increased platelet serotonin receptor density, and platelet activation is lower in nondepressed patients without ischemic heart disease than in nondepressed patients with ischemic heart disease. These markers are also found in higher levels in patients who have depressive symptoms. Although the investigators were unable to find a direct correlation between SSRIs and thrombus formation, they speculated that serotonin may play an important role in the pathogenesis not only of CAD but also of MI.