Predictors of Treatment Response Relapse and Recurrence in Major Depression

重度抑郁症治疗反应复发和复发的预测因素

• 批准号: 7793366
• 负责人: W. EDWARD CRAIGHEAD
• 金额: $ 137.05万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-02 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7793366
• 关键词: Achievement; Acute; Adult; Age; Alleles; Antidepressive Agents; Award; Behavior; Behavioral; Brain imaging; Cellular Neurobiology; Clinical Trials; Cognitive Therapy; Combination Drug Therapy; Combined Modality Therapy; Communicable Diseases; Communities; DSM-IV; Depressed mood; Depression and Suicide; Development; Disease; Disease remission; Disease susceptibility; Endocrine; Environment; Escitalopram; Evaluation; Feeling; Functional Magnetic Resonance Imaging; Funding; Genetic; Genetic Polymorphism; Glucocorticoid Receptor; Goals; Grant; Image; Imaging Techniques; Immune; Individual; Life; Long-Term Effects; Maintenance; Major Depressive Disorder; Measures; Medical; Medicine; Mental Depression; Molecular; Molecular Chaperones; Morbidity - disease rate; National Institute of Mental Health; Nature; Neurosecretory Systems; Outcome; Patients; Pattern; Personality; Personality Disorders; Pharmaceutical Preparations; Pharmacotherapy; Probability; Psychotherapy; Randomized; Recurrence; Relapse; Rest; Risk; Sample Size; Scanning; Science; Science of genetics; Selective Serotonin Reuptake Inhibitor; Substance abuse problem; Syndrome; Time; Treatment Protocols; Variant; Work; arm; base; chronic depression; depressive symptoms; design; developmental neurobiology; disability; duloxetine; improved; mortality; neurochemistry; non-drug; oncology; promoter; relating to nervous system; serotonin transporter; treatment effect; treatment program; treatment response; treatment trial

DESCRIPTION (provided by applicant): Major depression (MDD) is a highly prevalent disorder associated with significant morbidity and mortality and is estimated to be one of the leading causes of disability worldwide. The DSM-IV defined syndrome of MDD is a heterogeneous disorder characterized by a range of distinctive genetic, neural, and neuroendocrine diatheses and abnormalities. At the same time, individuals live and grow within an environment that influences developmental neurobiology, neurochemistry, and patterns of thought, feeling and behavior that further impact their vulnerability to the development of MDD. A variety of antidepressant drugs, psychotherapies, and non- drug somatic therapies have been demonstrated to be efficacious in acute treatment trials. The majority of patients in these trials, however, do not attain remission, increasing the risk for the development of chronic depression, suicide, substance abuse and several serious medical disorders. A major unmet need is the identification of predictors of remission to treatments, as has been utilized in other branches of medicine (e.g., oncology and infectious disease) to improve patient outcome. In view of advances in functional brain imaging, molecular and cellular neurobiology, genetics, and personality disorders and a number of promising findings in small studies, it is propitious to conduct studies to determine whether a concatenation of these factors predict antidepressant treatment remission as well as relapse and recurrence. In this application, we propose two studies. The first study is an expansion of our recently funded NIMH CIDAR 3-arm, 12-week treatment trial; we will increase the CIDAR sample size from 400 to 600 and follow all remitted patients for a total of two years. In this expanded study, 600 treatment na¿ve adult depressed patients will be randomized to one of the following treatments: 1) escitalopram, an SSRI; 2) duloxetine, an SNRI; and 3) CBT. The primary goal of the CIDAR is to employ a multivariate approach to predict remission following acute treatment with a single therapy. The primary purpose of study of this proposal is to identify predictors of relapse and recurrence during the 21 months following remission to these three monotherapy treatments. The second study is designed to study prediction of short-term and long-term effects of additional pharmacotherapy and psychotherapy combination treatments for those who fail to remit with monotherapy. Our group has made a number of advances in identifying imaging procedures (e.g., resting BOLD fMRI), genetic polymorphisms, and personality disorder measures that predict remission, relapse, and recurrence of MDD. In addition, we will employ additional state- of-the-science measures of MDD and its treatment. Statistically, we will seek to determine which measure and/or combination of measures leads to prediction of remission, relapse, and recurrence to the treatments under study. Delineation of predictors of treatment remission, relapse, and recurrence of MDD will dramatically improve patient outcomes and reduce the risk of inadequate treatment. Major Depressive Disorder has a lifetime occurrence rate of 16% and is among the most frequent and debilitating of all medical disorders. Despite considerable advances in understanding the causes, nature, and treatment of depression, we still do not know which treatment will work for an individual patient. As a result of the proposed studies, it is hoped that the community clinician of tomorrow will be able to prescribe a specific treatment for an individual patient with major depression, with confidence that the prescribed treatment will provide effective and lasting relief from the symptoms of depression.

描述（由申请人提供）：重度抑郁症 (MDD) 是一种高度流行的疾病，发病率和死亡率很高，估计是全世界残疾的主要原因之一。 DSM-IV 定义的 MDD 综合征是一种异质性疾病，其特征是一系列独特的遗传、神经和神经内分泌素质和异常。与此同时，个体生活和成长的环境会影响发育神经生物学、神经化学以及思维、感觉和行为模式，从而进一步影响他们患 MDD 的脆弱性。多种抗抑郁药物、心理疗法和非药物躯体疗法已在急性治疗试验中被证明是有效的。然而，这些试验中的大多数患者并未获得缓解，从而增加了患慢性抑郁症、自杀、药物滥用和几种严重疾病的风险。一个未满足的主要需求是确定治疗缓解的预测因子，这已在其他医学分支（例如肿瘤学和传染病）中用于改善患者的治疗效果。鉴于功能性脑成像、分子和细胞神经生物学、遗传学和人格障碍方面的进展以及小型研究中的许多有希望的发现，进行研究以确定这些因素的串联是否可以预测抗抑郁治疗的缓解以及复发和复发是有利的。在本申请中，我们提出了两项​​研究。第一项研究是我们最近资助的 NIMH CIDAR 3 臂、12 周治疗试验的扩展；我们将把 CIDAR 样本量从 400 增加到 600，并对所有缓解的患者进行为期两年的跟踪。在这项扩展研究中，600 名未接受过治疗的成年抑郁症患者将被随机接受以下治疗之一：1) 艾司西酞普兰，一种 SSRI； 2) 度洛西汀，一种 SNRI； 3) 认知行为治疗。 CIDAR 的主要目标是采用多变量方法来预测单一疗法急性治疗后的缓解情况。该提案研究的主要目的是确定这三种单一疗法缓解后 21 个月内复发和复发的预测因素。第二项研究旨在研究对单一疗法未能缓解的患者额外药物疗法和心理疗法联合治疗的短期和长期效果的预测。我们的小组在识别影像学程序（例如，静息 BOLD fMRI）、遗传多态性和预测 MDD 缓解、复发和复发的人格障碍测量方面取得了许多进展。此外，我们还将采用其他最先进的 MDD 及其治疗措施。从统计学上讲，我们将寻求确定哪种措施和/或措施组合可以预测所研究治疗的缓解、复发和复发。描述 MDD 治疗缓解、复发和复发的预测因素将显着改善患者的治疗结果并降低治疗不足的风险。重度抑郁症的终生发病率为 16%，是所有疾病中最常见、最使人衰弱的疾病之一。尽管在了解抑郁症的原因、性质和治疗方面取得了相当大的进展，但我们仍然不知道哪种治疗方法对个别患者有效。根据拟议的研究，希望未来的社区临床医生能够为重度抑郁症患者开出具体的治疗方案，并相信所开的治疗方案将有效且持久地缓解抑郁症的症状。