Late-life Depression and Cerebral Perfusion

Therapuetic Areas:Psychiatry / Psychology
Age Range:60 - Any
Start Date:December 2012
Contact:Dean Holbert

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The long-term goal is to determine if decreased blood flow to the brain (cerebral
hypoperfusion) is predictive of antidepressant outcomes in late-life depression (LLD).
Studies in younger adult report that successful antidepressant treatment is associated with
increases in cerebral blood flow, with no change in blood flow being observed in
nonresponders. Thus cerebral hypoperfusion may be a biomarker of poor response to
antidepressants. In LLD, this may occur secondarily to underlying vascular disease. If LLD
is characterized by cerebral hypoperfusion and it does have predictive power to identify
individuals who will poorly respond to conventional antidepressants, this would support the
study of interventions that improve cerebral perfusion and may improve antidepressant

As an initial step in this research, this pilot study will utilize MRI to examine if resting
blood flow deficits predict and persist with antidepressant nonremission in an elderly
population. The rationale for this proposal is that it will guide the design and power
requirements of a larger, definitive trial examining the relationship between cerebral
perfusion and depression outcomes. Importantly, support for this mechanism being linked to
LLD would also support studies examining the antidepressant efficacy of drugs that may
improve cerebral perfusion.

The primary purpose of this pilot study is a) to demonstrate feasibility by recruiting,
scanning, and treating depressed elders; and b) to acquire preliminary data for competitive
grant submissions.

SPECIFIC AIM: To use MRI to test for differences in cerebral perfusion between individuals
who do and do not remit to a 8-week course of sertraline.

After providing informed consent, participants will complete brain MRI and memory testing.
If they are currently taking an antidepressant and are not doing well on it, they will be
taken off it. Participants will then start sertraline, a commercially available
antidepressants. They will be monitored for response and side effects for 8 weeks and doses
adjusted as needed. After the study, we will examine how differences in brain blood flow
may predict who does and does not respond to sertraline.

Inclusion Criteria:

- Age 60 years or older.

- Current diagnosis of major depressive disorder (DSM-IV-TR), recurrent or chronic,
without psychotic features

- Minimum depression severity of Montgomery Asberg Depression Rating Scale (MADRS)
score ≥ 15

- Cognitively intact by Montreal Cognitive Assessment (MoCA) score ≥ 23

- Ability to read and write English

Exclusion Criteria:

- Other current or past psychiatric diagnoses

- Any use of illicit substances or abuse of prescription medications

- Presence of acute suicidality

- Current or past psychotic symptoms

- Known primary neurological disorder, including dementia

- Chronic untreated medical disorders where treatment is warranted

- Any contraindication to MRI, such as metal in the body

- Electroconvulsive therapy in the last 6 months

- Use of antidepressants or other psychiatric medications in the last month.

- Known allergy to sertraline

- A failed therapeutic trial of sertraline in the current depressive episode

- Current or planned psychotherapy
We found this trial at
2201 West End Ave
Nashville, Tennessee 37232
(615) 322-7311
Vanderbilt University Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education...
Nashville, TN
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