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: 7599071
• 负责人: W. EDWARD CRAIGHEAD
• 金额: $ 136.61万
• 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/7599071
• 关键词: Achievement; Acute; Adult; Age; Alleles; Antidepressive Agents; Award; Behavior; Behavioral; Brain imaging; Cellular Neurobiology; Clinical Trials; Combination Drug Therapy; Combined Modality Therapy; Communicable Diseases; Communities; DSM-IV; 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; 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; Upper arm; Variant; Work; base; chronic depression; cognitive behavior therapy; depressed; 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（由适用提供）：严重抑郁症（MDD）是一种高度流行的疾病，与显着的发病率和死亡率相关，估计是全球障碍的主要原因之一。 DSM-IV定义的MDD综合征是一种异质性疾病，其特征是一系列不同的遗传，神经元和神经内分泌核心和异常。同时，个人在影响发展神经生物学，神经化学以及思想，感觉和行为模式的环境中生活和成长，这进一步影响了他们对MDD发展的脆弱性。已证明各种抗抑郁药，心理治疗和非药物体细胞疗法在急性治疗试验中有效。但是，这些试验中的大多数患者都无法获得缓解，增加了慢性抑郁症，自杀，药物滥用和多种严重医疗疾病的发展风险。一个主要的未满足需要是确定治疗缓解的预测因素，如其他医学分支（例如肿瘤学和传染病）来改善患者预后。鉴于功能性脑成像，分子和细胞神经生物学，遗传学以及个人疾病的进步以及在小型研究中的许多有望的发现，有益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缓解以及救济和复发。在此应用中，我们提出了两项​​研究。第一项研究是扩展我们最近资助的NIMH Cidar 3臂，12周的治疗试验。我们将将CIDAR样本量从400增加到600，并关注所有汇款患者总共两年。在这项扩展的研究中，有600例成年抑郁症患者将被随机分为以下疗法之一：1）依他普兰（Escitalopram），SSRI； 2）Duloxetine，SNRI； 3）CBT。 CIDAR的主要目标是采用多元方法来预测单个治疗急性治疗后的缓解。研究该提案的主要目的是在缓解这三种单一治疗治疗后的21个月内确定救济和复发的预测指标。第二项研究旨在研究对未通过单一疗法促进的人的其他药物治疗和心理治疗联合治疗的短期和长期影响的预测。我们的小组在识别成像程序（例如静止fMRI），遗传多态性和人格障碍指标方面取得了许多进步，以预测MDD的缓解，继电器和复发。此外，我们还将采用MDD的科学测量及其治疗的其他状态。从统计上讲，我们将寻求确定测量的测量和/或组合导致预测所研究治疗方法的缓解，继电器和复发。划定治疗缓解，继电器和MDD复发的预测指标将大大改善患者的预后，并降低治疗不足的风险。重度抑郁症的终生发生率为16％，并且是所有医疗疾病的最常见和使人衰弱的事件之一。尽管在理解抑郁症的原因，性质和治疗方面取得了长足的进步，但我们仍然不知道哪种治疗方法对个别患者有效。由于拟议的研究，希望明天的社区临床能够为患有严重抑郁症患者的个体患者开出一种特定的治疗方法，并有信心，规定的治疗方法将为抑郁症症状提供有效而持久的缓解。