ENHANCING TREATMENT OUTCOMES IN DEPRESSION

在K02奖的竞争更新申请中，安德鲁·洛伊特博士提出了一系列旨在改善抑郁症治疗效果的研究和职业提升。25% - 40%的抑郁症患者对第一次服用抗抑郁药没有反应，这些患者可能会遭受长期的抑郁症。初步研究表明，可以在治疗前使用定量脑电图（QEEG）一致性测量脑功能，预测哪种抗抑郁药物最有可能使个体患者受益，也可以在治疗开始后在症状改善之前检测抗抑郁药物的有效性。该应用程序有三个具体目的：1)验证一致性在预测和检测两种具有不同作用机制的抗抑郁药的治疗反应方面的判别能力；2)建立相关测量与其他推定的抗抑郁反应预测因子的关系，包括脑代谢和脑结构以及临床因素（年龄和症状类型）；3)在发展目标方面，提高Leuchter博士在测量治疗结果和评估预测因子对治疗效果影响方面的技能。在他的主要研究中，Leuchter博士提出了一个计划，将招募96名年轻和年长的成人受试者进行双重屏蔽。受试者将接受氟西汀20/40 mg或文拉法辛150/225 mg的治疗，以确定一致性测量是否与抗抑郁药物的不同短期反应可靠相关。将检查治疗前后的FDG-PET、体积MRI测量和临床症状等推定的反应预测因素，以确定生理过程和结构特征，这些生理过程和结构特征有助于依从性与短期治疗结果之间的关联。这项研究是提高Leuchter博士在干预结果研究方面的研究活动和技能的整体计划的一部分。他将与两位顾问，博士。肯尼斯·韦尔斯和林恩·费尔班克斯，以实施新的方法并提高他在干预结果研究方面的技能。他将扩大他的研究，包括新的方法来检查反应模式，并将利用额外的功能结果测量。在这项研究的发展阶段，他还将启动一些项目，以检查依从性和其他假定的预测因素在改善长期治疗结果方面的有效性。这些有效性项目将包括在常规治疗环境中引入预测指标，并审查成本效益和长期治疗结果。

In this competing renewal application for a K02 award, Dr. Andrew Leuchter proposes a line of research and career enhancement aimed at improving outcomes of treatment for depression. Between 25 - 40 percent of patients with depression fail to respond to the first antidepressant prescribed, and these patients may suffer a protracted course of depression. Preliminary studies indicate that brain function measured with quantitative electroencephalographic (QEEG) cordance may be used prior to treatment, to predict which antidepressant medication is most likely to benefit an individual patient, as well as after treatment has started, to detect antidepressant effectiveness before symptoms improve. This application has three specific aims: 1) to verify the discriminative power of cordance in predicting and detecting treatment response for two antidepressants with different mechanisms of action; 2) to establish the relationship of cordance measurements to other putative predictors of antidepressant response, including cerebral metabolism and structure as well as clinical factors (age and symptom type); and, 3) in a developmental aim, to enhance Dr. Leuchter's skill in the areas of measuring treatment outcome and assessing the impact of predictors on treatment effectiveness. For his primary research study, Dr. Leuchter proposes a plan which will enroll 96 younger and older adult subjects in a double-masked protocol. Subjects will be treated with either fluoxetine 20/40 mg. or venlafaxine 150/225 mg., to determine whether cordance measurements are reliably associated with differential short-term response to antidepressant medications. Putative predictors of response such as pre- and post-treatment FDG-PET, volumetric MRI measurements, and clinical symptoms will be examined to identify the physiologic processes and structural features which contribute to the association between cordance and short-term treatment outcome. This study is part of an overall plan to enhance Dr. Leuchter's research activities and skills in interventions outcomes research. He will work with two consultants, Drs. Kenneth Wells and Lynn Fairbanks, to implement new methods and enhance his skills in intervention outcomes research. He will expand his research to include new methods to examine patterns of response, and will utilize additional functional outcome measures. In a developmental phase of this study, he also will initiate projects to examine the effectiveness of cordance and other putative predictors in improving long-term treatment outcomes. These effectiveness projects will include introduction of predictors into the usual treatment setting, and examination of cost-effectiveness and long-term treatment outcomes.