Optimizing an integrated whole-body hyperthermia and behavioral intervention for major depressive disorder

项目概要/摘要： 严重抑郁症困扰着全世界3亿多人，是导致残疾寿命损失的主要原因。目前的治疗方法在疗效上有很大的局限性，在药物治疗的情况下，还有很大的副作用。因此，迫切需要额外的有效，耐受性良好的治疗。一种这样的潜在治疗是全身热疗（WBH）。我们假设WBH与认知行为疗法（CBT）结合可能特别有效，CBT是一种公认的抑郁症治疗方法。这种组合可能会增加抑郁症患者的突然收益（抑郁症状的快速改善）。突然的收益预示着抑郁症的持久改善。在两个小样本的成年抑郁症患者中，单次WBH治疗会使抑郁症患者的积极情绪突然增加，这与认知灵活性的增加有关。尽管试点研究的初步数据令人鼓舞，但仍需要严格、精心设计的临床试验才能制定包括WBH在内的抑郁症治疗建议。特别是，研究人员还没有调查整合身心（CBT）干预作为抑郁症潜在综合治疗方法的潜力。我们的目的是在本提案中为此类试验奠定基础。在目标1（1期）中，我们将进行一项单组试验（N=16），以完善和优化WBH（每两周4次）与CBT（每周8次）相结合的程序。我们将在完成第一波n =8名受试者的所有程序后，在启动第二波n=8名受试者之前迭代完善程序。在第一阶段结束时，我们将完成第二阶段使用的综合干预组成部分的最终手册。在目标2（2期）中，我们将进行一项可行性试点试验（N=30），其中我们将参与者随机分配接受主动WBH（4个双周疗程）和CBT（8个每周疗程）干预或假WBH（4个双周疗程）仅CBT（8个每周疗程）。在前半部分入组完成后（n=15），我们将使用受试者和工作人员的反馈来完善剩余入组的程序（n=15;总共N=30）。这项可行性试点试验将测试招募和随机化程序，为重度抑郁症患者的多中心临床疗效试验做准备。这项工作对改善抑郁症的治疗和促进对情绪障碍综合身心疗法作用的理解具有重要意义。

Project Summary/Abstract: Major Depressive Disorder afflicts more than 300 million people worldwide and is the leading cause of life years lost to disability. Current treatments have important limitations in efficacy and, in the case of medication, substantial side-effects. There is thus a compelling need for additional effective, well-tolerated treatments. One such potential treatment is whole-body hyperthermia (WBH). We hypothesize that WBH may be particularly effective in combination with cognitive behavioral therapy (CBT), an established treatment for depression. This combination may increase sudden gains (rapid improvements in depression symptoms) in individuals with depression. Sudden gains predict durable improvements in depression. In two small samples of adults with depression, a single session of WBH precipitated sudden gains and acute increases in positive affect, which are associated with increases in cognitive flexibility, in individuals with depression. Despite promising initial data from pilot studies, rigorous, well-designed clinical trials are required in order to develop treatment recommendations for depression that include WBH. In particular, researchers have not investigated the potential of an integrated mind (CBT) and body (WBH) intervention as a potential integrative treatment approach for depression. We aim to lay the groundwork for such trials in this proposal. In Aim 1 (Phase 1), we will conduct a single-arm trial (N=16) to refine and optimize procedures for integrating WBH (4 bi-weekly sessions) with CBT (8 weekly sessions). We will iteratively refine procedures after completing all procedures for the first wave of n=8 participants before initiating the second wave of n=8 participants. At the end of Phase 1 we will complete a final manual for the combined intervention components for use in Phase 2. In Aim 2 (Phase 2) we will conduct a feasibility pilot trial (N=30) in which we randomize participants to receive active WBH (4 bi-weekly sessions) and CBT (8 weekly sessions) intervention or sham WBH (4 bi-weekly sessions) CBT only (8 weekly sessions). After the first half of enrollment is complete (n=15), we will use participant and staff feedback to refine procedures for the remaining enrollment (n=15; N=30 total). This feasibility pilot trial will test recruitment and randomization procedures in preparation for a multicenter clinical efficacy trial for participants with major depression. This work holds important promise to improve treatment of depression and advance understanding of the role of integrated mind-body therapies for mood disorders.