Connectivity Affecting the Antidepressant REsponse Study
Completed · Phase 4 · Has a placebo group
Conditions studied: Major Depressive Disorder
In brief
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.
Key facts
- Study ID
- NCT02332291
- Run by
- Vanderbilt University Medical Center
- People needed
- 95
- Starts
- 2015-04-01
- Expected to finish
- 2020-08-01
- Last updated by the study team
- 2021-09-21
Who can join
Age: 60 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- Age 60 years or older.
- Current diagnosis of major depressive disorder (DSM-IV-TR), single episode, recurrent or chronic, without psychotic features, as detected by Mini-International Neuropsychiatric Inventory (MINI) and clinical exam.
- Minimum MADRS score ≥ 15.
- Mini-Mental State Exam ≥ 24.
- Fluent in English.
You may not qualify if…
- Current or past diagnoses of other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) symptoms occurring during a depressive episode
- History of alcohol or drug dependence or abuse in the last three years
- History of developmental disorder or Intelligence Quotient score < 70
- Presence of acute suicidality
- Acute grief (< 1 month)
- Current or past psychosis
- Primary neurological disorder, including but not limited to dementia, stroke, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
- MRI contraindications
- Any physical or intellectual disability adversely affecting ability to complete assessments
- Electroconvulsive therapy in last 6 months
- Use of antidepressant medications or other psychotropic medications in the last 4 weeks (or the last 6 weeks for fluoxetine). Occasional use of benzodiazepines or non-benzodiazepine sedatives (such as zolpidem, eszopiclone, or zaleplon) during this period is allowable.
- A failed therapeutic trial of escitalopram in the current depressive episode (defined as at least 6 weeks of treatment at a daily dose of 10mg or higher)
- Known allergy or hypersensitivity to escitalopram or bupropion
- Current or planned psychotherapy
Where it is running
- Vanderbilt Psychiatric Hospital — Nashville, Tennessee, United States
Full record on ClinicalTrials.gov
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