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:
    7882839
  • 负责人:
  • 金额:
    $ 23.48万
  • 依托单位:
  • 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 2014-04-30
  • 项目状态:
    已结题

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. PUBLIC HEALTH RELEVANCE: Although there are now more than 20 different antidepressant medications available in the US, treatment resistant depression remains a common problem, with serious medical and economic consequences. The high rates of treatment resistant depression likely reflect the fact that existing antidepressant treatments were almost exclusively developed out of the monoaminergic hypothesis of depression pathophysiology and therefore largely share a common mechanism of action. The increasingly recognized limitations of this approach to antidepressant drug development provides a strong impetus for exploration of novel antidepressant treatments with unique targets of action such as that proposed in this study.
描述(由申请人提供):本协作R 01研究了谷氨酸调节和神经保护剂利鲁唑在难治性抑郁症(TRD)患者中的随机双盲安慰剂对照临床试验(RCT)的安全性和有效性。星星 *D研究的最新发现强调了这样一个事实,即我们目前基于单胺假说开发的抗抑郁药物具有严重的局限性。现在有新的证据表明,氨基酸神经递质(AANt)系统也可能有助于重度抑郁症(MDD)的病理生理学,靶向这些系统的药物可能具有有效的抗抑郁特性。阿曲唑目前已被美国FDA批准用于治疗肌萎缩侧索硬化症(ALS)。它已被证明对与药物的神经保护和可塑性增强特性相关的脑功能具有多种神经生物学作用。最近有两项开放标签研究显示利鲁唑对TRD有效,还有几份报告证明利鲁唑对双相抑郁症、广泛性焦虑症和强迫症有效。然而,尚未在TRD中进行RCT。这项随机、双盲、安慰剂对照试验采用序贯平行比较设计,评估了利鲁唑加强选择性5-羟色胺再吸收抑制剂西酞普兰治疗18-65岁中度TRD门诊患者的疗效和安全性。对公共卫生的意义:在这项独特的5年计划中,来自四个机构[耶鲁大学,MSSM,MGH和NIMH(MAP)]的研究人员将进行RCT,以检查连续利鲁唑治疗TRD的疗效,安全性和耐受性。证明利鲁唑的益处将代表难治性抑郁症患者的重大进展,并可能有助于阐明我们对MDD的病理生理学和抗抑郁作用机制的理解。最直接的是,由于利鲁唑已经是FDA批准的药物,已被安全地处方给数千名ALS患者,这项研究的积极结果可以迅速传播到临床实践中,并鼓励进一步研究这种策略。证明利鲁唑在TRD中的疗效将为发现未来的靶向多巴胺能系统的药物打开大门,这些药物可用于对抗这种常见的破坏性疾病。 公共卫生相关性:虽然现在美国有20多种不同的抗抑郁药物,但难治性抑郁症仍然是一个常见的问题,具有严重的医疗和经济后果。难治性抑郁症的高发生率可能反映了这样一个事实,即现有的抗抑郁药治疗几乎完全是从抑郁症病理生理学的单胺能假说发展而来的,因此在很大程度上具有共同的作用机制。越来越多地认识到这种方法的局限性,以抗抑郁药物的开发提供了一个强大的动力,探索新的抗抑郁药物治疗与独特的行动目标,如本研究中提出的。

项目成果

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SANJAY J MATHEW其他文献

SANJAY J MATHEW的其他文献

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{{ truncateString('SANJAY J MATHEW', 18)}}的其他基金

Ketamine for Treatment Resistant Late-Life Depression
氯胺酮治疗难治性晚年抑郁症
  • 批准号:
    8925545
  • 财政年份:
    2015
  • 资助金额:
    $ 23.48万
  • 项目类别:
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
  • 批准号:
    8269776
  • 财政年份:
    2010
  • 资助金额:
    $ 23.48万
  • 项目类别:
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
  • 批准号:
    8114118
  • 财政年份:
    2010
  • 资助金额:
    $ 23.48万
  • 项目类别:
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
  • 批准号:
    8463246
  • 财政年份:
    2010
  • 资助金额:
    $ 23.48万
  • 项目类别:
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
  • 批准号:
    8472813
  • 财政年份:
    2010
  • 资助金额:
    $ 23.48万
  • 项目类别:
Optimization of IV Ketamine for Treatment Resistant Major Depression
静脉注射氯胺酮治疗难治性重度抑郁症的优化
  • 批准号:
    8270516
  • 财政年份:
    2009
  • 资助金额:
    $ 23.48万
  • 项目类别:
CONTINUATION RILUZOLE IN PREVENTION OF RELAPSE FOLLOWING KETAMINE IN DEPRESSION
继续利鲁唑预防抑郁症服用氯胺酮后复发
  • 批准号:
    7953696
  • 财政年份:
    2009
  • 资助金额:
    $ 23.48万
  • 项目类别:
Optimization of IV Ketamine for Treatment Resistant Major Depression
静脉注射氯胺酮治疗难治性重度抑郁症的优化
  • 批准号:
    7900029
  • 财政年份:
    2009
  • 资助金额:
    $ 23.48万
  • 项目类别:
Optimization of IV Ketamine for Treatment Resistant Major Depression
静脉注射氯胺酮治疗难治性重度抑郁症的优化
  • 批准号:
    8102809
  • 财政年份:
    2009
  • 资助金额:
    $ 23.48万
  • 项目类别:
Optimization of IV Ketamine for Treatment Resistant Major Depression
静脉注射氯胺酮治疗难治性重度抑郁症的优化
  • 批准号:
    7728054
  • 财政年份:
    2009
  • 资助金额:
    $ 23.48万
  • 项目类别:

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