The Effect of Problem Solving Therapy and Antidepressant Therapy on Cerebral Perfusion and Brain Derived Neurotropic Factor in Depressed Elders
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- change in cerebral perfusion
研究概览
简要总结
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.
详细描述
Subjects: subjects will have non-psychotic unipolar major depression based on DSM IV criteria (Structured Clinical Interview for DSM IV; SCID)and be 65 years or older and will have depression of moderate or greater depression severity (Hamilton Depression Rating Scale score > or = 19. Depression severity will be assessed with the clinician rated Hamilton Depression Rating Scale (HDRS) and the subject rated Quick Inventory of Depressive Symptoms (QIDS). Ratings will be performed weekly for the first month and then every 2 weeks until the end of the trial.
Neuroimaging: The MRI studies included in this protocol are commonly utilized in clinical practice. In addition to conventional structural MRI, this protocol will utilize techniques developed to evaluate cerebral blood flow (arterial spin labeling), white matter integrity (diffusion tensor imaging), and brain biochemistry (MR spectroscopy) and will be performed using a 4 Tesla magnet. Imaging will be performed at the VAMC/UCSF Center for Imaging of Neurodegenerative Disease (CIND) under the direction of Michael Weiner, M.D. Brain derived neurotropic factor (BDNF): a blood sample will be drawn pretreatment to determine the serum concentration of BDNF. This test will be repeated post-treatment. The assay for BDNF will be performed in the laboratory of Synthia Mellon, Ph.D at UCSF. Serum will be assayed for BDNF in duplicate, using a commercial BDNF ELISA assay kit (R&D Systems, Minneapolis, MN, USA).
Cognition will be assessed with a battery of neuropsychological tests including the Stroop Color-Word Test, the Trail Making Test: A and B; Dementia Rating Scale I/P; Boston Naming Test, and the Hopkins Verbal Learning Test-Short.
Treatment assignment: If patients have a preference for PST or sertraline, they will receive that treatment. If they have no preference, they will be randomized to one or the other until 19 subjects have been assigned to each treatment.
Sertraline, a selective serotonin reuptake inhibitor (SSRI), will be administered as the antidepressant. It will be started at 25 mg/day for one week and then increased to 50 mg and continued for 3 weeks. At the end of 4 weeks if the patient has had limited response, the dose will be increased to 100 mg/day. At 8 weeks if response is limited, dose will be increased to 150 mg/day. At any time, the dose can be lowered for tolerability reasons.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •history of psychosis
- •failure to respond to sertraline or PST during the episode
- •allergic to sertraline
研究组 & 干预措施
problem solving therapy
subjects will receive 12 weeks of weekly problem solving therapy
干预措施: problem solving therapy (Behavioral)
sertraline
12 weeks of sertraline
干预措施: Sertraline (Drug)
结局指标
主要结局
change in cerebral perfusion
时间窗: study endpoint (8-12 weeks)
Change in cerebral perfusion from baseline to study endpoint in frontal brain regions.
次要结局
- Change in cognitive measures of memory, learning, and executive dysfunction(Baseline to study endpoint (8-12 weeks))
- Change in BDNF(8-12 weeks)