Major Depressive Disorder | The Effect of Problem Solving Therapy and Antidepressant Therapy on Cerebral Perfusion and Brain Derived Neurotropic Factor (BDNF) in Depressed Elders
Major Depressive Disorder research study
What is the primary objective of this study?
The focus of this study is to gather preliminary data regarding the effects of a psychological therapy—Problem Solving Therapy—and an antidepressant medication—sertraline—on 1) cerebral perfusion (CP), 2) brain derived neurotrophic factor (BDNF), and 3) measures of cognitive function in subjects with late life major depression (LLMD). This research goal will be achieved by recruiting 38 individuals over the age of 65 with LLMD. The primary outcomes will be change in CP, change in BDNF, and change in cognitive measures from baseline to the end of 12 weeks of either therapy. We will also examine predictors of treatment outcome including severity of executive dysfunction, baseline BDNF concentrations, and baseline CP measures. The baseline neuropsychological testing, brain imaging, and depression assessment will be obtained in a companion study (PI S. Mackin; CHR #H42689-32681-01) that is IRB approved and is already in progress. In the current study a baseline serum BDNF level will be added to Dr. Mackin's protocol. Patients will then receive either 12 weeks of Problem Solving Therapy or antidepressant treatment with sertraline. Both treatments are evidence based and commonly administered in our clinic. Outcome variables will be measures of depression severity, the BDNF serum concentration, cerebral perfusion using a MRI arterial spin labeling (ASL) technique and cognitive changes in memory and executive dysfunction. This is a preliminary or pilot study. The primary objectives are to determine if the methods appear feasible and to determine if change in BDNF or CP occur after treatment and secondarily to determine if there are changes in cognitive functioning. The study is not powered to show differences between treatments. The hypotheses are 1) PST will result in increased perfusion in frontal regions of the brain but that frontal perfusion will not change with sertraline; 2)sertraline will result in an increase in BDNF but PST will not. Change in cognitive measures of memory, learning, and executive dysfunction will be examined on an exploratory basis.
Who is eligible to participate?
Inclusion Criteria: - clinical diagnosis of DSM IV non-psychotic unipolar major depression - depression severity > or = to 19 on HDRS - age 65 years or older - able to provide informed consent Exclusion Criteria: - history of psychosis - failure to respond to sertraline or PST during the episode - allergic to sertraline
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Major Depressive Disorder
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Behavioral:problem solving therapy12 weeks of weekly 45 minute sessions of problem solving therapy
Drug:Sertraline12 weeks of sertraline; 25 mg for one week, 50 mg for 3 weeks; then 100 mg/day for 4 weeks; then 150 mg/day for 4 weeks based on tolerability and response
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
problem solving therapysubjects will receive 12 weeks of weekly problem solving therapy
sertraline12 weeks of sertraline
Start Date: March 2011
Completed Date: June 2016
Primary Outcome: change in cerebral perfusion
Secondary Outcome: Change in cognitive measures of memory, learning, and executive dysfunction
Study sponsors, principal investigator, and references
Principal Investigator: J. Craig Nelson, MD
Lead Sponsor: University of California, San Francisco
Collaborator: Leon J. Epstein Endowment