Effect of Brain Lesion Severity on Treatment Response in Late-Life Depression

Duke University

Status

Completed

Conditions

Depression

Treatments

Drug: Sertraline

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00339066

2524

R01MH062158 (U.S. NIH Grant/Contract)

DATR A4-GPX

Details and patient eligibility

About

This study will determine the relationship between brain lesion severity, treatment response, and frontal lobe brain function in people with late-life depression (LLD).

Full description

Depression in older adults is a major public health problem and it often goes underdiagnosed and undertreated. A significant number of people with LLD, especially those with cerebrovascular risk factors, have subcortical grey matter and frontal deep white matter brain lesions. Some studies suggest that these lesions, or hyperintensities, may be associated with poor acute and long-term depression treatment response. Similarly, studies have shown that people with LLD frequently have functional deficits in the frontal lobe portion of their brains. This dysfunction has been shown to be associated with poor acute treatment response with a tricyclic antidepressant drug, as well as with a greater risk for depression relapse. The applicability of these findings to other classes of antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), however, remains unknown. Additionally, more information is needed about the interaction between frontal brain lesions and executive function deficits in LLD. This study will determine the relationship between brain lesion severity, treatment response, and frontal lobe function in people with late-life depression who are being treated with the SSRI sertraline.

Participants in this open label study will first undergo neuropsychological testing to determine eligibility. All eligible participants will be treated with sertraline for 12 weeks. Dosages will begin at 25 mg per day, and will be increased to 50 mg per day after 4 days. Any other dosage modifications will depend on the participant's individual response to the medication. All participants will have an MRI scan at some point during the study. Assessments of symptoms and treatment response will occur at the study site biweekly until Week 8, and then again at Week 12.

Enrollment

131 patients

Sex

All

Ages

60+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

DSM-IV of major depressive disorder (MDD)
Score of greater than 20 on the MADRS (score of greater than 17 for atypical depression)
Score of greater than 20 on the Mini Mental State Examination (MMSE)

Exclusion criteria

Any condition that may make having an MRI medically inadvisable
Any severe or unstable medical conditions
Any known primary neurological disorders, including history of stroke
Any other simultaneous Axis I disorder
History of substance or alcohol abuse disorder within 6 months prior to study entry
Currently at risk for suicide
History of failed prior adequate trials of two antidepressants for the current depressive episode
History of failed prior adequate trial of sertraline
Current use of any other psychoactive medications (medication washout will be required)