RESPONSE VARIABILITY IN TREATMENT RESISTANT DEPRESSION

难治性抑郁症的反应差异

• 批准号: 7067593
• 负责人: JONATHAN Edward ALPERT
• 金额: $ 29.91万
• 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 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067593
• 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 项目的多中心协作辅助研究的修订，其中我们建议研究生物标志物，这些生物标志物可能通过前瞻性识别难治性抑郁症 (TRD) 患者来帮助指导治疗。来自随机临床试验和自然治疗的初步数据表明，定量脑电图 (QEEG) 测量（一致性）与药物治疗的反应和无反应相关。治疗早期前额叶活动的变化可以预测后期的反应。初步数据表明，使用一致性指标的生物标志物模型可以识别（a）对 STAR*D 方案第 2 级规定的治疗有抵抗力的患者，以及（b）最初但非持续的患者，“类似安慰剂”的反应。这种前瞻性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。该提案中的修订包括扩展使用 cordance 生物标志物的基本原理、有关 STAR*D 方案的更多细节、额外的试点数据以及经过细化以反映最近 STAR*D 注册数据的主题流预测。该项目的三个具体目标是：（1）评估神经生理学生物标志物在有效性治疗试验环境中的使用的可接受性和成本效益； (2) 确定一致性指标在前瞻性识别对其 2 级治疗选择有抵抗力的抑郁症患者中的有效性； (3) 检查这些指标在识别治疗不会​​产生持续反应的患者方面的用途。我们将测试具体假设：(1) QEEG 评估是可接受的，并在有效性治疗试验中提供成本有效的指导； (2) 2级对特定转换或增强策略的急性治疗反应将通过2级治疗前两周前额叶协调性的变化来预测； (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。当 72 名抑郁症受试者在两个 STAR*D 中心之一进入方案第 2 级治疗时，将被招募，其中加州大学洛杉矶分校神经精神病学研究所和哈佛大学马萨诸塞州总医院各 36 名。 QEEG 数据将在 2 级开始时和另外两周后记录。治疗临床医生和受试者将对生理数据不知情，并且将使用 STAR*D 方案中不可或缺的仪器来评估结果。受试者将在完成 2 级后 3 个月和 6 个月进行随访，以评估反应是否持续。比例检验和 t 检验将用于评估可接受性和成本效益。将使用卡方和线性回归模型来测试急性反应的预测。对两个地点的数据进行独立检查将用于评估 cordance 生物标志物方法的普遍性。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测试。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一致性变化与患者和疾病因素以及功能结果的关系。