Psychobiologic Factors of the Placebo Response in MDD

描述（由申请人提供）：重度抑郁症（MDD）是所有医学疾病中安慰剂反应率最高的疾病之一。在临床试验中，许多接受安慰剂治疗的重度抑郁症患者表现出与接受抗抑郁药物治疗的患者相当的改善。先前的研究表明，人际因素和患者特征是抑郁症药物和安慰剂反应的基础，这使得重度抑郁症成为理解安慰剂反应起源的一个很好的疾病模型。这一应用提出了一系列临床研究，将阐明人际因素和患者特征在改善安慰剂治疗重度抑郁症中的作用。本研究将达到以下四个具体目的：1)确定服用安慰剂或药物药丸是否对重度抑郁症患者的症状改善以及人际临床相互作用（ICI）有影响；2)确定预处理期望和药物治疗联盟强度是否与人际临床相互作用、安慰剂和药物治疗条件下临床改善的可能性相关；3)确定重度抑郁症患者是否存在与安慰剂反应相关的预处理神经生理、症状或认知特征；4)研究人际临床互动、安慰剂和药物治疗对重度抑郁症患者脑功能的影响。我们将通过三步研究计划来实现这些目标。首先，我们将招募120名符合中度至中度重度复发性重度抑郁症标准的受试者，并将其纳入三种治疗条件之一：1)人际临床互动（ICI）（彻底的基线评估，受试者在固定的时间表上与临床研究人员互动）；2)安慰剂治疗（PBO）（评估和相互作用，如ICI加安慰剂片双盲治疗）；3)药物治疗（MED）（如ICI加抗抑郁药物双盲治疗的评估和相互作用）。其次，所有受试者将在治疗前进行评估，包括与研究人员的药物治疗联盟、对治疗的期望、认知处理速度、抑郁的情绪和神经植物症状以及脑电活动。第三，受试者将在8周的治疗过程中接受评估，包括症状变化评分、药物治疗联盟、期望和脑功能的变化。在8周结束时，盲人将被打破，所有受试者将被转介进行自然治疗，他们将有资格免费接受10个月的药物治疗。除了测试特定的假设，我们计划进行探索性分析，其中我们将检查可能影响安慰剂反应的因素，如人格特征、感知社会支持和健康控制点。该项目的结果将有助于更好地理解重度抑郁症中安慰剂反应的机制。

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) has among the highest placebo response rates of any medical illness. Many MDD subjects in clinical trials who undergo treatment with placebo show improvement comparable to those receiving antidepressant medication. Previous research indicates that interpersonal factors and patient characteristics underlie both medication and placebo response in depression, making MDD an excellent illness model for understanding the origins of the placebo response. This application proposes a line of clinical investigation that will elucidate the role of interpersonal factors and patient characteristics in contributing to improvement seen in placebo treatment of MDD. This study will achieve the following four specific aims: 1) to determine whether administration of placebo or medication pills has effects on improvement of symptoms in addition to interpersonal clinical interaction (ICI) for subjects with MDD; 2) to determine whether pretreatment expectations and the strength of the pharmacotherapeutic alliance are related to the likelihood of clinical improvement during interpersonal clinical interaction, placebo, and medication treatment conditions; 3) to determine if there are pretreatment neurophysiologic, symptom, or cognitive characteristics of subjects that are associated with response to placebo in MDD; and, 4) to examine the effects of interpersonal clinical interaction, placebo pill administration, and medication administration, on brain function in subjects with MDD. We will achieve these aims through a three-step research plan. First, we will enroll 120 subjects meeting criteria for moderate to moderately severe recurrent MDD into one of three treatment conditions: 1) interpersonal clinical interaction (ICI) (thorough baseline assessment and subjects interacting with clinical research personnel on a fixed schedule); 2) placebo treatment (PBO) (assessment and interaction as in ICI plus double-blinded treatment with placebo tablets); and 3) medication treatment (MED) (assessment and interaction as in ICI plus double blinded treatment with antidepressant medication). Second, all subjects will be assessed prior to treatment assignment with measures of pharmacotherapeutic alliance with study personnel, expectation regarding treatment, cognitive processing speed, emotional and neurovegetative symptoms of depression, as well as brain electrical activity. Third, subjects will be assessed over the course of eight weeks of treatment with ratings of symptom change, as well as changes in pharmacotherapeutic alliance, expectation, and brain function. At the end of eight weeks, blind will be broken and all subjects referred for naturalistic treatment where they will be eligible to receive medication free-of charge for 10 months. In addition to testing the specific hypotheses, we plan an exploratory analysis in which we will examine factors that may influence placebo response, such as personality characteristics, perceived social support, and health locus of control. The results of this project will lead to better understanding of the mechanisms of the placebo response in MDD.