Cardiovascular Effects of Agomelatine and Escitalopram in Patients With Major Depressive Disorder (MDD)
Status:
Unknown status
Trial end date:
2015-02-01
Target enrollment:
Participant gender:
Summary
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
psychological effects.
Findings from this study will assist us to identify of biological correlates of sympathetic
nervous activation which will enable us to: (1) identify those at potentially increased
cardiac risk, and (2) potentially implement additional therapeutic strategies in order to
reduce cardiac risk. Indeed, it is not known whether antidepressant treatment alone would be
sufficient to reverse any adverse effects of sympathetic nervous activation. This study aims
to answer this important clinical question.
Phase:
Phase 4
Details
Lead Sponsor:
Baker Heart and Diabetes Institute Baker IDI Heart and Diabetes Institute
Collaborators:
Monash Medical Centre Servier Laboratories (Australia) Pty Ltd The Alfred