Psychobiologic Factors of the Placebo Response in MDD

描述(由申请人提供)：严重抑郁障碍(MDD)是所有内科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MDD受试者表现出与接受抗抑郁药物治疗的患者相当的改善。以前的研究表明，抑郁症的药物反应和安慰剂反应都是由人际因素和患者特征决定的，这使得MDD成为了解安慰剂反应起源的一个很好的疾病模型。这项申请提出了一系列临床调查，将阐明人际因素和患者特征在促进MDD安慰剂治疗中的改善中所起的作用。这项研究将达到以下四个具体目标：1)确定服用安慰剂或药片是否对MDD患者的人际临床互动(ICI)以外的症状有改善作用；2)确定治疗前的期望和药物治疗联盟的强度是否与人际临床互动、安慰剂和药物治疗条件下临床改善的可能性有关；3)确定MDD患者是否存在与安慰剂反应有关的预治疗神经生理学、症状或认知特征；以及4)检查人际临床互动、安慰剂丸和药物治疗对MDD患者大脑功能的影响。我们将通过分三步走的研究计划来实现这些目标。首先，我们将120名符合中度至中度复发MDD标准的受试者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，受试者按固定时间表与临床研究人员互动)；2)安慰剂治疗(PBO)(评估和互动，如ICI中的评估和互动，加上安慰剂片剂的双盲治疗)；以及3)药物治疗(MED，评估和互动，如ICI中的评估和互动，加抗抑郁药物的双盲治疗)。其次，所有受试者将在治疗分配之前进行评估，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、抑郁症的情绪和神经植物性症状以及脑电活动。第三，受试者将在八周的治疗过程中根据症状变化以及药物治疗联盟、预期和脑功能的变化进行评估。在八周结束时，失明将被打破，所有受试者将被转介接受自然疗法，在那里他们将有资格接受为期10个月的免费药物治疗。除了检验特定的假设外，我们还计划进行一项探索性分析，考察可能影响安慰剂反应的因素，如个性特征、感知到的社会支持和健康控制源。该项目的结果将有助于更好地理解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.