2/3-Efficacy and Tolerability of Riluzole in Treatment-Resistant Depression

2/3-利鲁唑治疗难治性抑郁症的疗效和耐受性

基本信息

批准号：
8463246
负责人：
SANJAY J MATHEW
金额：
$ 22.31万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8463246
关键词：
Address Adverse effects Adverse event Age Amino Acid Neurotransmitters Aminobutyric Acids Amyotrophic Lateral Sclerosis Antidepressive Agents Anxiety Anxiety Disorders Bipolar Depression Case Series Citalopram Clinical Clinical Treatment Clinical Trials Clinical trial protocol document Collection Conduct Clinical Trials Controlled Clinical Trials DNA Data Analyses Data Collection Databases Disease Double-Blind Method Drug Targeting Event FDA approved Feedback Functional disorder Funding Future Generalized Anxiety Disorder Genes Genetic Genetic Materials Genetic Polymorphism Glutamatergic Agents Glutamates Human Subject Research Hydrochloride Salt Industry Institution Investigation Knowledge Leadership Legal patent Life Link Major Depressive Disorder Manuscripts Measurement Measures Medical Economics Mental Depression Mental Health Mental disorders Modeling Montgomery and Asberg depression rating scale Mood Disorders Moods Multi-Institutional Clinical Trial National Institute of Mental Health Neurobiology Neuronal Plasticity Neuroprotective Agents Neurotransmitters Obsessive-Compulsive Disorder Orphan Drugs Outpatients Patient Recruitments Patients Persons Pharmaceutical Preparations Pilot Projects Placebo Control Placebos Policies Population Positioning Attribute Preparation Procedures Property Public Health Publishing Randomized Reporting Research Research Design Research Personnel Research Project Grants Resistance Resources Retrieval Riluzole Role Safety Sample Size Sampling Selective Serotonin Reuptake Inhibitor Site Structure System Teleconferences Testing Training Translational Research Treatment Protocols Voting base clinical practice cost effective data management depressive symptoms design double-blind placebo controlled trial drug development experience fighting improved innovation interest jun Oncogene meetings member metabolomics monoamine neuropsychiatry novel open label pre-clinical preclinical study programs public health relevance response statistics translational study treatment response

项目摘要

DESCRIPTION (provided by applicant): This collaborative R01 investigates the safety and efficacy of the glutamate-modulating and neuroprotective agent riluzole in a randomized double-blind placebo-controlled clinical trial (RCT) in patients with treatment- resistant depression (TRD). The recent findings of the STAR*D study highlight the fact that our current armamentarium of antidepressant medications, developed out of the monoamine hypothesis, has serious limitations. There is now emerging evidence that amino acid neurotransmitter (AANt) systems may also contribute to the pathophysiology of major depressive disorder (MDD), and that drugs targeting these systems may have potent antidepressant properties. Riluzole is currently approved by the US FDA for the treatment of amyotrophic lateral sclerosis (ALS). It has been shown to have a variety of neurobiological effects on glutamatergic function associated with the drug's neuroprotective and plasticity-enhancing properties. There have now been two recent open-label studies showing riluzole to be effective in TRD as well as several reports demonstrating riluzole's efficacy in bipolar depression, generalized anxiety disorder, and obsessive-compulsive disorder. However, no RCT has been performed in TRD. This randomized, double-blind, placebo-controlled trial, using a sequential parallel comparison design, evaluates the efficacy and safety of riluzole augmentation of the selective serotonin reuptake inhibitor citalopram in outpatients ages 18-65 with moderate TRD. Significance to Public Health: In this unique 5-year proposal, investigators from four institutions [Yale, MSSM, MGH and NIMH (MAP)] will conduct a RCT to examine the efficacy, safety and tolerability of adjunctive riluzole treatment in TRD. Demonstration of riluzole's benefit would represent a major advance for patients with difficult-to-treat depression, and may help elucidate our understanding of the pathophysiology of MDD and the mechanism of antidepressant action. Most immediately, since riluzole is already a FDA-approved medication that has been safely prescribed to thousands of patients with ALS, positive findings from this study could rapidly disseminate into clinical practice and would encourage further investigation of this strategy. Demonstrating riluzole's efficacy in TRD would open the door to the discovery of future medications targeting the glutamatergic system that could be used to fight this common and devastating disorder.

描述（由申请人提供）：该协作R01调查了在随机的双盲安慰剂对照临床试验（RCT）中，谷氨酸调节和神经保护剂riluzole在耐药抑郁症患者中的安全性和功效。 Star*d研究的最新发现强调了一个事实，即我们当前的抗抑郁药的武器库是由单胺假说开发的，具有严重的局限性。现在有新的证据表明，氨基酸神经递质（AANT）系统也可能有助于主要抑郁症（MDD）的病理生理，并且针对这些系统的药物可能具有有效的抗抑郁剂特性。 Riluzole目前已获得美国FDA的批准，用于治疗肌萎缩性侧面硬化症（ALS）。已显示它对与药物的神经保护性和可塑性增强特性相关的谷氨酸能功能具有多种神经生物学作用。现在已经进行了两项开放标签的研究，表明Riluzole在TRD中有效，并显示了Riluzole在躁郁症抑郁症，普遍焦虑症和强迫症中的功效。但是，在TRD中没有进行RCT。这项使用顺序平行比较设计的随机，双盲，安慰剂对照试验评估了riluzole增强选择性5-羟色胺再摄取抑制剂西耐普兰在18-65岁的门诊患者中的疗效和安全性。对公共卫生的意义：在这一独特的5年提案中，来自四个机构[YALE，MSSM，MGH和NIMH（MAP）]的研究人员将进行RCT，以检查TRD中辅助性Riluzole治疗的功效，安全性和耐受性。 Riluzole益处的证明将代表难以治疗抑郁症患者的重大进步，并可能有助于阐明我们对MDD病理生理学的理解和抗抑郁作用的机制。大多数情况下，由于Riluzole已经是FDA批准的药物，已安全地向数千名ALS患者开了处方，因此这项研究的阳性发现可能会迅速传播到临床实践中，并鼓励对该策略进行进一步研究。证明Riluzole在TRD中的功效将为发现针对谷氨酸能系统的未来药物打开大门，该药物可用于抵抗这种常见和毁灭性的疾病。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Longer-term open-label study of adjunctive riluzole in treatment-resistant depression.

辅助利鲁唑治疗难治性抑郁症的长期开放标签研究。

DOI：
10.1016/j.jad.2019.06.065
发表时间：
2019
期刊：
Journal of affective disorders
影响因子：
6.6
作者：
Sakurai,Hitoshi;Dording,Christina;Yeung,Albert;Foster,Simmie;Jain,Felipe;Chang,Trina;Trinh,Nhi-Ha;Bernard,Richard;Boyden,Sean;Iqbal,SyedZ;Wilkinson,SamuelT;Mathew,SanjayJ;Mischoulon,David;Fava,Maurizio;Cusin,Cristina
通讯作者：
Cusin,Cristina