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
• 负责人: SANJAY J MATHEW
• 金额: $ 0.93万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953696
• 关键词: Acute; Address; Adult; Adverse effects; Affinity; Anesthesia procedures; Anesthetics; Animal Model; Anti-Anxiety Agents; Antidepressive Agents; Attenuated; Childhood; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Dose; Double-Blind Method; Excitatory Amino Acid Antagonists; Exhibits; Funding; Grant; Institution; Intervention; Intravenous; Investigation; Ketamine; Maintenance; Major Depressive Disorder; Mood Disorders; Morbidity - disease rate; N-Methylaspartate; Neurocognitive; Outcome Measure; Pain management; Patients; Phase; Pilot Projects; Placebo Control; Placebos; Property; Protocols documentation; Randomized; Relapse; Research; Research Personnel; Resistance; Resources; Riluzole; Role; Sample Size; Source; Therapeutic; Time; Unipolar Depression; United States National Institutes of Health; depression; depressive symptoms; disorder later incidence prevention; efficacy testing; experience; lamotrigine; mortality; response; treatment strategy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 11/28/2006 Existing treatments for major depressive disorder (MDD) generally take several weeks to several months to exert their maximal benefit. Given the morbidity and mortality resulting from depressive symptoms, there is an urgent need to develop rapidly-acting treatments, as well as to identify optimal continuation treatment approaches. Ketamine, a high-affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard anesthetic agent for many years in both pediatric and adult patients, with doses as high as 2 mg/kg IV. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine has antidepressant and anxiolytic effects in animal models, and may have rapid antidepressant properties for patients with severe mood disorders. Indeed, a recent placebo-controlled investigation replicated an earlier pilot study (Berman et al 2000), and demonstrated robust antidepressant efficacy of a single dose of ketamine (0.5 mg/kg) in patients with treatment-resistant unipolar depression (Zarate et al 2006). A high proportion of these patients maintained the acute response to IV ketamine for several days or longer. To capitalize on the therapeutic promise of IV ketamine for MDD, several issues will be addressed in this new study. First, it is crucial to identify safe and effective continuation and maintenance treatment strategies following IV ketamine. Second, we need to develop pharmacological strategies that attenuate the acute neurocognitive side effects of IV ketamine, in order to enhance overall patient acceptability. Finally, clinical experience with IV ketamine in treatment-resistant MDD in larger sample sizes is necessary to identify moderators of response, to ultimately target the most appropriate candidates for this intervention. This research protocol will test the efficacy of riluzole (100 mg/day), in patients with treatment-resistant unipolar major depressive disorder (MDD) who exhibit an acute, sustained response to a single dose of intravenous (IV) racemic ketamine (0.5 mg/kg over 40 minutes). The efficacy of pretreatment with lamotrigine to attenuate IV ketamine's side effects will also be examined. We propose to randomize approximately 50 acute IV ketamine responders to riluzole (n=25) or placebo (n=25) in a 4-week, randomized, double-blind, continuation-phase study. The main outcome measure is time to relapse of depression.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 2006年11月28日 现有的重度抑郁症（MDD）治疗通常需要数周到几个月才能发挥其最大收益。鉴于抑郁症状导致的发病率和死亡率，迫切需要开发快速作用的治疗方法，并确定最佳的延续治疗方法。 氯胺酮是一种高亲和力的N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂，在儿科和成人患者中多年来一直用作标准麻醉剂，剂量高达2 mg/kg/kg IV。 除了其在麻醉和疼痛管理中的良好作用外，还有新的证据表明，氯胺酮在动物模型中具有抗抑郁药和抗焦虑作用，并且可能对严重情绪障碍患者具有快速的抗抑郁特性。 实际上，最近的安慰剂对照研究复制了一项早期的试点研究（Berman等，2000），并证明了单剂量氯胺酮（0.5 mg/kg）的耐药性抗抑郁疗效的耐药性疗效（Zarate等，2006年）。 这些患者中很大一部分维持对IV氯胺酮的急性反应几天或更长时间。 为了利用IV氯胺酮对MDD的治疗承诺，这项新研究将解决一些问题。 首先，至关重要的是要确定静脉注射氯胺酮后安全有效的延续和维护治疗策略。 其次，我们需要制定药理学策略，以减轻静脉氯胺酮的急性神经认知副作用，以增强患者的整体可接受性。 最后，对于识别反应的主持人，必须针对此干预措施的最合适的候选者，在耐药的MDD中具有静脉注射氯胺酮在耐药的MDD中的临床经验是必要的。 该研究方案将测试Riluzole（100 mg/day）的疗效，对具有治疗的单极重大抑郁症（MDD）患者，他们表现出对单剂量静脉内（IV）静脉内（IV）外星型氯胺酮（40分钟内0.5 mg/kg）表现出急性，持续反应的。 还将检查使用Lamotrigine预处理减轻IV氯胺酮的副作用的功效。 我们建议将大约50个急性IV氯唑反应者随机化为Riluzole（n = 25）或安慰剂（n = 25），进行为期4周，随机，双盲，持续相位研究。 主要结果指标是抑郁症复发的时间。