RESPONSE VARIABILITY IN TREATMENT RESISTANT DEPRESSION

难治性抑郁症的反应差异

• 批准号: 6882688
• 负责人: JONATHAN Edward ALPERT
• 金额: $ 30.63万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-08 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882688
• 关键词: behavior therapy; behavioral /social science research tag; biomarker; clinical research; cost effectiveness; diagnosis design /evaluation; electroencephalography; human subject; human therapy evaluation; longitudinal human study; major depression; mental disorder diagnosis; neuropsychology; outcomes research; patient care management; patient oriented research; prognosis; questionnaires; therapy design /development

DESCRIPTION (provided by applicant): This is a revision of our multi-site collaborative Ancillary Study to the STAR*D Project, in which we propose to study biomarkers that may help guide treatment by prospectively identifying patients with treatment resistant depression (TRD). Pilot data from both randomized clinical trials and naturalistic treatment show that a quantitative electroencephalographic (QEEG) measure, cordance, is associated with response and nonresponse to pharmacotherapy; changes in prefrontal activity early in treatment are predictive of later response. Preliminary data suggest that a biomarker model using the cordance indicator can identify (a) patients who will be resistant to treatment prescribed in Level 2 of the STAR*D protocol, and (b) patients who will have an initial but non-sustained, "placebo-like" response. Such prospective identification would allow physicians to undertake more sophisticated regimens earlier and attain improved clinical outcome. The revisions in this proposal include expansion of the rationale for using the cordance biomarker, additional detail about the STAR*D protocol, additional pilot data, and subject flow projections that have been refined to reflect recent STAR*D enrollment figures. The three specific aims of this project are: (1) to evaluate the use of neurophysiologic biomarkers in an effectiveness treatment trial setting for acceptability and cost effectiveness; (2) to ascertain the validity of cordance indicators in prospectively identifying depressed patients who will be resistant to their Level 2 treatment choices; and (3) to examine the use of these indicators in identifying patients who will not have a sustained response to treatment. We will test specific hypotheses: (1) assessment with QEEG will be acceptable and offer cost effective guidance in an effectiveness treatment trial; (2) acute treatment response in Level 2 to specific switching or augmentation strategies will be predicted by changes in prefrontal cordance in the first two weeks of Level 2 treatment; and (3) sustained treatment response will be predicted by changes in prefrontal values after two weeks of treatment. 72 subjects with depression will be recruited when they enter treatment in Level 2 of the protocol at either of two STAR*D sites, 36 each at UCLA's Neuropsychiatric Institute and Harvard's Massachusetts General Hospital. QEEG data will be recorded at the start of Level 2 and after two additional weeks. Treating clinicians and subjects will be blinded to physiologic data, and outcomes will be assessed using the instruments integral to the STAR*D protocol. Subjects will be followed-up at 3 and 6 months after completing Level 2 to assess whether responses are sustained. The test of proportion and t-tests will be used to evaluate acceptability and cost effectiveness. Prediction of acute response will be tested with chi square and linear regression models. Independent examination of the data at the two sites will be used to assess the generalizability of the cordance biomarker method. The relationship of our biomarkers to sustained response will be tested by chi square analyses. Secondary analyses will use general linear models and growth mixture modeling to examine how early cordance changes relate to patient and illness factors and to functional outcomes.

描述(由申请人提供)：这是我们对STAR*D项目的多地点协作辅助研究的修订版，在该项目中，我们建议通过前瞻性地识别患有难治性抑郁症(TRD)的患者来研究可能有助于指导治疗的生物标记物。来自随机临床试验和自然主义治疗的先导数据表明，定量脑电(QEEG)测量Cordance与药物治疗有效和无效有关；治疗早期额叶活动的变化预示着后期反应。初步数据表明，使用Cordance指示器的生物标记物模型可以识别(A)将对STAR*D方案第2级中规定的治疗产生抵抗力的患者，以及(B)将有初始但非持续的“安慰剂样”反应的患者。这种前瞻性的识别将使医生能够更早地采取更复杂的治疗方案，并获得更好的临床结果。这项提案中的修订包括扩大使用Cordance生物标记物的理由、关于STAR*D方案的更多细节、额外的试点数据以及为反映最近的STAR*D登记数字而进行的主题流预测。该项目的三个具体目标是：(1)评估神经生理学生物标记物在有效治疗试验环境中的使用，以确定可接受性和成本效益；(2)确定Cordance指标在前瞻性识别将抵制其二级治疗选择的抑郁症患者方面的有效性；以及(3)检查这些指标在确定对治疗不会有持续反应的患者方面的使用。我们将测试具体的假设：(1)定量脑电图的评估将是可接受的，并在有效性治疗试验中提供成本效益指导；(2)水平2对特定转换或增强策略的急性治疗反应将通过第二水平治疗的头两周前额神经的变化来预测；(3)持续的治疗反应将通过治疗两周后前额叶值的变化来预测。72名抑郁症患者将在两个STAR*D网站中的任何一个进入方案的二级治疗时被招募，加州大学洛杉矶分校的神经精神病学研究所和哈佛大学的马萨诸塞州综合医院各36个。QEEG数据将在第二级开始时和额外两周后记录。治疗临床医生和受试者将对生理数据视而不见，结果将使用STAR*D方案中不可或缺的仪器进行评估。受试者将在完成第二级后的3个月和6个月进行跟踪，以评估反应是否持续。将使用比例检验和t检验来评估可接受性和成本效益。急性反应的预测将用卡方和线性回归模型进行检验。将对这两个地点的数据进行独立检查，以评估Cordance生物标记物方法的普适性。我们的生物标志物与持续反应的关系将通过卡方分析进行检验。二次分析将使用一般线性模型和生长混合模型来检查早期音量变化与患者和疾病因素以及功能结果的关系。