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Low heart rate variability is a marker of increased risk of cardiac mortality, and is observed in depressed coronary artery disease patients. Some antidepressants may themselves, however, decrease heart rate variability. We will test the hypothesis that greater reduction in heart rate variability will be associated with duloxetine (which has noradrenergic activity) than escitalopram (a selective serotonin reuptake inhibitor). We will also test the hypothesis that changes in heart rate variability are related to the magnitude of norepinephrine transporter occupancy.
Evaluation of heart rate variability (HRV) has been shown to be a valuable tool for measuring autonomic dysfunction associated with depression and with cardiac disease. Low HRV is a marker of increased risk of cardiac mortality, and is observed in depressed coronary artery disease patients and in anxious patients post-MI. Treatment with sympathomimetic antidepressants, such as MAO inhibitors and tricyclics, reduce HRV further, and have been associated with elevated heart rate, orthostatic hypotension, and with adverse cardiac events. Although there is increasing evidence that the selective serotonin reuptake inhibitor (SSRI) class of antidepressants have minimal effects on the cardiovascular system, the case is less clear with the SNRI antidepressants which block the reuptake of both serotonin and norepinephrine. It is possible that measures of the extent of norepinephrine transporter blockade or inhibition may relate to the HRV reduction seen with noradrenergic drugs. Given these considerations, we propose a study to compare the cardiovascular profile of the SSRI escitalopram (Lexapro), with the most recently available SNRI, duloxetine, in outpatients with depression. Using HRV methodology, we will test the hypothesis that greater reduction in HRV will be associated with duloxetine than escitalopram. In addition, we will measure the magnitude of serotonin and norepinephrine transporter occupancy produced by each drug. This will allow us to examine the relationship between changes in HRV to the magnitude of transporter inhibiting effects of each drug.
Allocation: Randomized, Control: Placebo Control, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Major Depressive Disorder
duloxetine vs. escitalopram
Duke University Medical Center
Published on BioPortfolio: 2014-08-27T03:49:09-0400
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A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309)
Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.
An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.
Depressive states usually of moderate intensity in contrast with major depression present in neurotic and psychotic disorders.
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