Connectivity Affecting the Antidepressant REsponse Study
Status:
Completed
Trial end date:
2020-08-01
Target enrollment:
Participant gender:
Summary
It can be difficult to achieve remission in individuals with late-life depression (LLD) and
they often require aggressive treatment. This challenge is in part due to age-related
vascular changes that are common in LLD. Successful antidepressant treatment involve changes
across affective, cognitive, and default mode networks. We hypothesize that in LLD, vascular
disease adversely affects response to antidepressants by disrupting connectivity of these
networks. The primary goal of this project is to characterize how focal vascular damage
affects regional connectivity and response to antidepressants. Based on past work and pilot
data, we a priori focus on the cingulum bundle and uncinate fasciculus. These key fiber
bundles connect frontal, temporal, and cingulate regions involved in cognition and affective
responses. Our central hypothesis is that ischemic damage to the cingulum bundle and uncinate
fasciculus contributes to structural and functional connectivity deficits of those tracts.
This results in a disconnection effect that alters the function of connected regions. In
turn, this increases the risk of a poor response to antidepressants.
Our approach is to enroll up to 130 adults over age 60 years with a diagnosis of Major
Depressive Disorder. Subjects will complete clinical evaluation, cognitive testing, and
MRI/functional MRI (fMRI) sessions, including an fMRI emotional oddball task that includes
attentional and affective components. Participants will be stratified by cerebral lesion
severity and randomized in a 2:1 ratio to a double-blinded 8-week trial of escitalopram or
matching placebo. Those who do not remit will transition to an 8-week trial of open-label
bupropion, an antidepressant with a different mechanism of action. This will allow us to
determine if different and distinct circuit deficits affect response to antidepressants with
different mechanisms of action while also accounting for the placebo response.
Phase:
Phase 4
Details
Lead Sponsor:
Vanderbilt University Vanderbilt University Medical Center