Mechanisms of Antidepressant Non-Response in Late-Life Depression
2020年6月30日 更新者：Bret Rutherford、New York State Psychiatric Institute
This project seeks to elucidate the mechanisms by which antidepressant medications have limited efficacy in Late Life Depression (LLD) in order to develop new treatment interventions for this prevalent and disabling illness.
Investigators hypothesize that the presence of executive dysfunction (ED),which is common in depressed adults over 60, impairs the ability to form appropriate expectancies of improvement with antidepressant treatment.
Greater expectancy has been shown to improve antidepressant treatment outcome and is hypothesized to be a primary mechanism of placebo effects.
Moreover, white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are more prevalent in patients with LLD compared to healthy controls.
It has been argued that WMH contribute to the pathogenesis of LLD with ED and decrease the efficacy of antidepressant medications by disrupting connections between prefrontal cortical (PFC) and subcortical structures.
Vascular lesions to white matter tracts may also compromise the pathway by which expectancy-based placebo effects influence depressive symptoms.
Expectancies reflect activation in PFC areas that may improve depressive symptoms by modulating the activity of subcortical regions subserving negative affective systems (i.e., amygdala) as well as those important in reward and hedonic capacity (nucleus accumbens and ventral striatum).
Thus, LLD patients with ED and WMH may sustain a "double-hit" to their ability to experience placebo effects in antidepressant treatments: ED diminishes the ability to generate appropriate treatment expectancies, while WMH disrupt the physiologic pathways by which expectancies lead to improvement in depressive symptoms.
研究概览
详细说明
To determine whether decreased antidepressant medication response in LLD patients with ED and WMH is caused by a loss of expectancy effects, Investigators will evaluate 130 outpatients with LLD at baseline to determine their degree of ED (interference score on Stroop Color-Word Test), WMH burden (severity score on Fazekas modified Coffey Rating Scale derived from anatomical MRI), and white matter tract integrity (using diffusion tensor imaging [DTI]).
Building on work from the investigators K23 Award, the investigator will manipulate participants' expectancy of improvement in an 8-week duration antidepressant trial by randomizing patients between open administration of escitalopram (i.e., high expectancy) and placebo-controlled administration of escitalopram (i.e., low expectancy).
The difference in antidepressant response observed between open and placebo-controlled medication treatment is a measure of the expectancy contribution to outcome, which is substantial in younger depressed adults but investigators hypothesize this will be diminished in LLD patients with ED and WMH.
研究类型
介入性
注册 (实际的)
138
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
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New York
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New York、New York、美国、10032
- New York State Psychiatric Institute
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
60年 至 90年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Men and women aged 60-90 years
- Diagnosis with nonpsychotic Diagnostic and Statistical Manual (DSM) IV MDD
- 24-item Hamilton Rating Scale for Depression (HRSD) score ≥ 16
- Willing to and capable of providing informed consent and complying with study procedures
Exclusion Criteria:
- Current comorbid Axis I DSM IV disorder other than Nicotine Dependence, Adjustment Disorder, or Anxiety Disorder
- diagnosis of substance abuse or dependence (excluding Nicotine Dependence) within the past 12 months
- History of psychosis, psychotic disorder, mania, or bipolar disorder
- Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease
- MMSE < 24
- HRSD suicide item > 2 or Clinical Global Impressions (CGI)-Severity score of 7 at baseline
- history of allergic or adverse reaction to escitalopram, or non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20mg) during the current episode
- current treatment with psychotherapy, antidepressants, antipsychotics, or mood stabilizers
- having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures (i.e., severe obesity, claustrophobia)
- acute, severe, or unstable medical or neurological illness
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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安慰剂比较：Double Blind-Placebo
Blinded treatment with placebo, one pill a day.
If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.
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Inert substance or treatment which is designed to have no therapeutic value but resemble the active medication in this study
其他名称：
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有源比较器：Double Blind-Escitalopram
Blinded treatment with either escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted.
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Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.
It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
其他名称：
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有源比较器：Open Treatment with Escitalopram
Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4.
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Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.
It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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汉密尔顿抑郁量表 (HRSD)
大体时间：基线
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我们的目标是通过汉密尔顿抑郁量表 (HRSD) 衡量的抑郁症状。
HRSD 是一份包含 24 个项目的问卷，用作抑郁症的指示和评估恢复的指南。
总分范围为 0-74，不包括非典型症状子量表。
16 分或以上的分数通常被认为表明存在抑郁症状。
分数越高表明严重程度越高。
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基线
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Hamilton Rating Scale for Depression (HRSD)
大体时间：Week 8
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Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD).
The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery.
Total scores range from 0-74, not including atypical symptoms sub-scale.
A score of 16 or above is typically considered to indicate the presence of depressive symptoms.
Higher scores indicate greater severity.
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Week 8
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Quick Inventory of Depressive Symptoms (QIDS-SR)
大体时间：Baseline
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QIDS-SR is a 16 item scale self-report form that was used to measure depression outcomes.
This self-report is valuable in this study, because it is less susceptible to clinician and rater bias.
The QIDS-SR has been increasingly used in antidepressant studies due to its equivalent weightings for each symptom item, clearly understandable anchor points, and inclusion of all DSM criteria for depression.
The scores range from 0-27 with 27 being worse depressive symptoms.
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Baseline
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Quick Inventory of Depressive Symptoms (QIDS-SR)
大体时间：Week 8
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QIDS-SR is a 16 item scale self-report form that was used to measure depression outcomes.
This self-report is valuable in this study, because it is less susceptible to clinician and rater bias.
The QIDS-SR has been increasingly used in antidepressant studies due to its equivalent weightings for each symptom item, clearly understandable anchor points, and inclusion of all DSM criteria for depression.
The scores range from 0-27 with 27 being worse depressive symptoms.
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Week 8
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Credibility and Expectancy Scale-Better (CES)
大体时间：Pre-Baseline
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CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement.
The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies.
Question 2 ('Better') asks the patient the chances of their depression being completely better at the end of this study, from 1 = very poor to 7 = very good.
The higher the number, the higher the expectancy that they will be better.
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Pre-Baseline
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Credibility and Expectancy Scale-Better (CES)
大体时间：Week 0
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CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement.
The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies.
Question 2 ('Better') asks the patient the chances of their depression being completely better at the end of this study, from 1 = very poor to 7 = very good.
The higher the number, the higher the expectancy that they will be better.
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Week 0
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Credibility and Expectancy Scale-Depression
大体时间：Pre-baseline
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CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement.
The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies.
CES question 3 ('Depression') asks how the patient's depression will be at the end of the study, compared with now, from 1 = much worse to 7= much better.
The higher the number, the higher the expectancy that their depression will be much better.
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Pre-baseline
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Credibility and Expectancy Scale-Depression
大体时间：Week 0
|
CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement.
The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies.
CES question 3 ('Depression') asks how the patient's depression will be at the end of the study, compared with now, from 1 = much worse to 7= much better.
The higher the number, the higher the expectancy that their depression will be much better.
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Week 0
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Quick Inventory of Depression Scale (QIDS-SR): Expectancy
大体时间：Pre-Baseline
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This 16-items assessment is used to rate the 9 criterion symptom domains of a major depressive episode: 4 items are used to rate sleep disturbance (early, middle, and late insomnia plus hypersomnia); 2 items are used to rate psychomotor disturbance (agitation and retardation); 4 items are used to rate appetite/weight disturbance (appetite increase or decrease and weight increase or decrease).
Only 1 item is used to rate the remaining 6 domains (depressed mood, decreased interest, decreased energy, worthlessness/guilt, concentration/decision making, and suicidal ideation).
Each item is rated 0-3.
For symptom domains that require more than 1 item, the highest score of the item relevant for each domain is taken.
The total score ranges from 0-27.
A lower rating indicates higher expectancy of improvement and lower expectation of depressive symptomatology, and a higher rating indicates lower expectancy of improvement, higher expectation of depression.
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Pre-Baseline
|
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Quick Inventory of Depression Scale (QIDS-SR): Expectancy
大体时间：Week 0
|
This 16-items assessment is used to rate the 9 criterion symptom domains of a major depressive episode: 4 items are used to rate sleep disturbance (early, middle, and late insomnia plus hypersomnia); 2 items are used to rate psychomotor disturbance (agitation and retardation); 4 items are used to rate appetite/weight disturbance (appetite increase or decrease and weight increase or decrease).
Only 1 item is used to rate the remaining 6 domains (depressed mood, decreased interest, decreased energy, worthlessness/guilt, concentration/decision making, and suicidal ideation).
Each item is rated 0-3.
For symptom domains that require more than 1 item, the highest score of the item relevant for each domain is taken.
The total score ranges from 0-27.
A lower rating indicates higher expectancy of improvement and lower expectation of depressive symptomatology, and a higher rating indicates lower expectancy of improvement, higher expectation of depression.
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Week 0
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Executive Dysfunction: Stroop Color Word
大体时间：Pre-Baseline
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Stroop Color Word test asks patients to name the color of a word rather than reading the word.
Stroop Color Word is how many colors they can name in 45 sec (higher is better, e.g., less executive dysfunction).
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Pre-Baseline
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Executive Dysfunction: Stroop Interference
大体时间：Pre-Baseline
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The Stroop is a measure of inhibition under distracting conditions that is sensitive to frontal lobe dysfunction.
in Stroop Color Word test patients are to name the color of a word rather than reading the word.
Stroop Color Word is how many colors they can name in 45 sec (higher is better, e.g., less executive dysfunction).
Stroop Interference is this score adjusted for age and education.
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Pre-Baseline
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White Matter Hyperintensity (WMH) Outcome- Total WMH
大体时间：Pre-Baseline
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Magnetic Resonance Imaging (MRI) of the Brain was acquired.
We rated the severity of WMH on axial T2 FLAIR images using the Fazekas modified Coffey Rating Scale.
Deep WMH are scored as 0 (absent), 1 (punctate foci), 2 (beginning confluence of foci), and 3 (large confluent areas); subcortical gray matter HIs (basal ganglia) are scored as 0 (absent), 1 (punctate), 2 (multipunctate), and 3 (diffuse); periventricular HIs are scored as 0 (absent), 1 (caps), 2 (smooth halo), and 3 (irregular and extending into the deep white matter).
Our primary measure of WMH burden will be DWMH score, which has been used to establish the only empirically validated diagnostic criteria for vascular depression, where scores of 0-1 were normal, but 2-3 indicated WHM.
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Pre-Baseline
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2014年2月19日
初级完成 (实际的)
2019年1月17日
研究完成 (实际的)
2020年1月17日
研究注册日期
首次提交
2013年8月26日
首先提交符合 QC 标准的
2013年8月26日
首次发布 (估计)
2013年8月29日
研究记录更新
最后更新发布 (实际的)
2020年7月2日
上次提交的符合 QC 标准的更新
2020年6月30日
最后验证
2020年6月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.