Effects of Duloxetine vs. Escitalopram on Heart Rate Variability in Depression

NCT ID: NCT00215228

Last Updated: 2014-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2007-08-31

Brief Summary

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.

Detailed Description

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.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

duloxetine vs. escitalopram

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• adults 20-60 years of age
• a primary diagnosis of depression using DSM-IV criteria
• written informed consent
• a negative serum pregnancy test for women of childbearing potential

Exclusion Criteria

• history of cardiovascular disease
• history of hypertension
• history of bipolar disorder
• history of schizophrenia or other psychotic disorder
• alcohol or other substance abuse within the last 3 months
• history of cognitive impairment

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Zhang, M.D., Ph. D

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

6957-05-3R0

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00007159

Identifier Type: -

Identifier Source: org_study_id