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应答率最高的疾病之一。在临床试验中，许多接受安慰剂治疗的MDD受试者显示出与接受抗抑郁药物治疗的受试者相当的改善。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，使MDD成为了解安慰剂反应起源的极好疾病模型。本申请提出了一系列临床研究，将阐明人际因素和患者特征在促进MDD安慰剂治疗改善中的作用。本研究将实现以下四个具体目标：1）确定对于MDD受试者，除了人际临床相互作用（ICI）外，安慰剂或药物药丸的给药是否对症状改善有影响; 2）为了确定治疗前期望和药物联盟的强度是否与人际临床互动期间临床改善的可能性相关，安慰剂，和药物治疗条件; 3）确定是否存在与MDD中对安慰剂的反应相关的受试者的治疗前神经生理学、症状或认知特征;和，4）检查人际临床相互作用、安慰剂药丸施用和药物施用对MDD受试者的脑功能的影响。我们将通过三步研究计划实现这些目标。首先，我们将招募120名符合中度至中度重度复发性MDD标准的受试者，接受以下三种治疗条件之一：1）人际临床相互作用（ICI）（彻底的基线评估和受试者按固定时间表与临床研究人员互动）; 2）安慰剂治疗（PBO）（如ICI加用安慰剂片剂的双盲治疗中的评估和相互作用）;和3）药物治疗（MED）（如ICI加用抗抑郁药物的双盲治疗中的评估和相互作用）。其次，在治疗分配之前，将评估所有受试者，测量与研究人员的药物合作、治疗预期、认知处理速度、抑郁症的情绪和植物神经症状以及脑电活动。第三，将在八周的治疗过程中评估受试者的症状变化，以及药物组合、期望和脑功能的变化。在8周结束时，将破盲，所有受试者将接受自然治疗，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，我们将检查可能影响安慰剂反应的因素，如人格特征，感知的社会支持和健康控制点。该项目的结果将有助于更好地了解MDD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.