Vortioxetine in Patients With Major Depressive Disorder and Coronary Artery Disease

Coronary Artery Disease Clinical Trial

Official title: An 8-week, Open-Label Clinical Trial of the Efficacy and Safety of Vortioxetine in Patients With Major Depressive Disorder and Coronary Artery Disease

Status Withdrawn

Clinical Trial Summary

This is a preliminary, open-label, clinical trial designed to assess the efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients with coronary artery disease. In addition, the study will assess the effects of vortioxetine on heart rate variability in these patients.

Clinical Trial Description

Comorbid Major Depressive Disorder (MDD) and Coronary Artery Disease (CAD) are common:

Major depressive disorder is a highly prevalent disorder that is serious, and in some cases life-threatening, condition. The 12-month prevalence of major depressive disorder in the United States is 6.6% (Kessler et al., 2003). Coronary artery disease (CAD) is also a large and growing problem in the United States. According to the 2014 American Heart Association (AHA) report on heart disease and stroke statistics, an estimated 15.4 million Americans ≥20 years of age have coronary artery disease. The total prevalence of coronary artery disease in this population is estimated to be 6.4%, with a prevalence of 7.9% in men and 5.1% in women. By the year 2030, the prevalence of coronary artery disease is projected to increase approximately 18% from 2013 estimates (Go et al., 2014). Thus, patients with major depressive disorder and comorbid CAD represent a large population of patients.

Depression in patients with CAD is clinically important:

Depression frequently accompanies coronary artery disease and has been linked more somatic symptoms, hospitalizations, increased financial burden, and poorer quality of life, as well as being a predictor of worse outcomes of cardiac disease. Reduction of cardiac risk factors is less likely to be successful in depressed patients. Depression may also interfere with medication adherence, as depressed patients are three times as likely to be noncompliant with their medication regimens. In addition, depression is associated with decreased rates of participation in cardiac rehabilitation, higher healthcare utilization and costs, and greatly reduced quality of life (Lichtman et al., 2009). Due to these effects of depression on coronary artery disease, there is increasing recognition that depression should be formally considered a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014).

Thus, there is a great, unmet clinical need to treat patients with major depressive disorder and coronary artery disease.

In addition to the older tricyclic antidepressants, the newer serotonin-norepinephrine reuptake inhibitors are also associated with cardiovascular risks like hypertension, orthostatic hypotension, and perhaps QTc prolongation (Mago et al., 2014). Vortioxetine is a newly approved antidepressant thought to work by combining modulation of 5-HT receptor subtypes and inhibition of the serotonin transporter (Citrome, 2014). Early data suggests that this multimodal mechanism of action results in increased brain levels of serotonin, dopamine, and noradrenaline in the prefrontal cortex (Pehrson et al., 2013). Clinical trials of vortioxetine for major depressive disorder have not shown any cardiovascular adverse effects (Mago et al., 2014).

Heart Rate Variability (HRV) Heart Rate Variability is a measure is based on the changes in the interval between consecutive heart beats and between consecutive instantaneous heart rates. It has become the conventionally accepted term to describe variations of both instantaneous heart rate and RR intervals. Long term reduced heart rate variability can lead to immune dysfunction and inflammation, cardiovascular disease and mortality (Newhouse, 2014). Several studies in depressive patients have shown reduced heart rate variability that suggests an increased sympathetic activity and/or reduced vagal activity (Carney et al., 2009). Thus, treating depression effectively may reduce heart rate variability, which is a surrogate marker for better cardiovascular outcomes.

The proposed study has been planned as a pilot, open-label study of the use, for the first time, of vortioxetine in patients with documented coronary disease. Therefore, the sample size is not based on a formal sample size calculation but on feasibility of a small study that, if positive, can lead to a future larger, adequately powered study. A sample size of 25 patients is appropriate for the present purpose. The results of this proposed study would inform sample size calculation for a future, larger study. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder
• Myocardial Ischemia

• NCT number: NCT02454426
• Study type: Interventional
• Source: Thomas Jefferson University
• Status: Withdrawn
• Phase: Phase 0
• Start date: April 2016
• Completion date: June 2016