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

• ClinicalTrials.gov Identifier: NCT00215228
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Last Update Posted: July 21, 2014
• Sponsor: Duke University
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: duloxetine vs. escitalopram	Phase 2; Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Effects of Escitalopram vs. Duloxetine on Heart Rate Variability and Autonomic Cardiovascular Control
• Study Start Date: July 2005
• Actual Study Completion Date: August 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Effect of treatment on heart rate variability

Secondary Outcome Measures :

1. Effect of treatment on affective variables (depression, anxiety, stress reactivity)
2. Effect of treatment on neurotransmitter transporter occupancy

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Duke University

Forest Laboratories

Investigators

• Principal Investigator: Wei Zhang, M.D., Ph. D; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00215228
• Other Study ID Numbers: Pro00007159; 6957-05-3R0 ( Other Identifier: DUMC )
• First Posted: September 22, 2005
• Last Update Posted: July 21, 2014
• Last Verified: September 2007

Additional relevant MeSH terms:

Depressive Disorder; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Duloxetine Hydrochloride; Citalopram; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Peripheral Nervous System Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Analgesics; Sensory System Agents; Dopamine Agents