Cardiovascular Effects of Agomelatine and Escitalopram in Patients With Major Depressive Disorder (MDD)

There is strong evidence that patients with major depressive disorder (MDD) are at increased risk of developing coronary heart disease (CHD). This elevated risk is independent of classical risk factors such as smoking, obesity, hypercholesterolemia, diabetes and hypertension. The risk of CHD is increased 1½-2 fold in those with minor depression and 3-4½ fold in subjects with MDD. Put simply, the relative risk of developing CHD is proportional to the severity of the depression. While the mechanism of increased cardiac risk attributable to MDD is not known disturbances in autonomic function most likely do play a part. In untreated patients with MDD (with no underlying CHD) the investigators have identified that a marked sympathetic nervous activation and diminished heart rate variability (HRV) occurs in a proportion (approximately one third) of patients. Diminished HRV has been linked to increased incidence rates of acute cardiac events in conditions such as hypertension, diabetes and myocardial infarction. Importantly, whether treating depression actually improves the risk of: (1) CHD development or (2) recurrence of cardiac events in patients with existing CHD remains unknown. The investigators, and others, have provided a growing body of evidence linking elevated sympathetic activity and exaggerated sympathetic responses to stress to early stages of end organ dysfunction and markers of disease development. Of particular note, in addition to possible effects on HRV is the association of chronic sympathetic nervous activation to: (a) abnormal blood pressure regulation and (b) the development of insulin resistance. The investigators therefore plan to examine the cardiovascular effects of two different antidepressant medications, agomelatine and escitalopram, in patients with MDD. In addition, the investigators plan to investigate the effects these two medications have on sympathetic nervous system activity, blood pressure, HRV, endothelial function, metabolic and p