CONTINUOUS INTRAVENOUS KETAMINE IN MAJOR DEPRESSIVE DISORDER

重度抑郁症持续静脉注射氯胺酮

• 批准号: 7718201
• 负责人: Dennis S. Charney
• 金额: $ 2.68万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718201
• 关键词: Acute; Address; Adult; Affinity; Anesthesia procedures; Anesthetics; Antidepressive Agents; Brain; Childhood; Computer Retrieval of Information on Scientific Projects Database; Dose; Effectiveness; Ensure; Excitatory Amino Acid Antagonists; Exhibits; Failure; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Grant; Individual; Institution; Intravenous; Investigation; Ketamine; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mental Depression; Mood Disorders; Moods; Morbidity - disease rate; N-Methylaspartate; Outcome Measure; Outpatients; Pain management; Patients; Pharmaceutical Preparations; Pilot Projects; Placebo Control; Property; Protocols documentation; Relapse; Research; Research Personnel; Resistance; Resources; Rest; Role; Source; Standards of Weights and Measures; Testing; Therapeutic; Time; Treatment Protocols; Unipolar Depression; United States National Institutes of Health; Week; blood oxygenation level dependent response; day; depressive symptoms; mortality; response

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. 10/11/2007 Existing treatments for major depressive disorder (MDD) generally take weeks to months to exert their maximal benefit. Given the morbidity and mortality resulting from failure to treat depressive symptoms in a timely fashion, there is an urgent need to develop rapidly-acting treatments, as well as to identify optimal continuation treatment approaches. Ketamine, a high-affinity NMDA glutamate receptor antagonist, has been used as a standard intravenous (IV) anesthetic agent for many years in both pediatric and adult patients, with doses as high as 2 mg/kg. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine 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 showed a robust acute antidepressant effect of a single dose of ketamine (0.5 mg/kg) in patients with treatment-resistant unipolar depression (Zarate et al., 2006), with many patients maintaining a mood improvement for several days. In order to fully capitalize on the therapeutic promise of IV ketamine for treatment resistant depression (TRD), two new issues will be addressed in this present study. First, it is important to identify the effectiveness of repeated doses of IV ketamine, in order to possibly prolong the antidepressant response beyond the acute effect of each individual administration. Second, it is crucial to identify the maximally effective while minimally aversive dose of IV ketamine that can be safely administered to outpatients over repeated doses. Patient acceptability of the drug regimen is key in ensuring the possible sustained benefit of IV ketamine. A final question pertains to the effect of ketamine treatment (both single and repeated dosing) on brain activity. We are adding functional imaging to this protocol in order to investigate (1) treatment-induced changes in task-related BOLD responses measured using functional magnetic resonance imaging (fMRI) and (2) treatment-induced changes in resting-state connectivity measured using functional connectivity MRI (fcMRI). This research protocol will test the efficacy of repeated IV ketamine administration in 20 patients with treatment-resistant MDD who exhibit an acute response to a single dose of IV ketamine. The dose to be used for repeated administration will be determined using the single-dose response. The main outcome measure is time to relapse following the antidepressant response to repeated dosing.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 2007年10月11日 现有的重度抑郁症 (MDD) 治疗通常需要数周至数月才能发挥最大疗效。 鉴于未能及时治疗抑郁症状导致的发病率和死亡率，迫切需要开发快速起效的治疗方法，并确定最佳的持续治疗方法。 氯胺酮是一种高亲和力 NMDA 谷氨酸受体拮抗剂，多年来一直被用作儿科和成人患者的标准静脉 (IV) 麻醉剂，剂量高达 2 mg/kg。 除了其在麻醉和疼痛管理中的既定作用之外，越来越多的证据表明氯胺酮可能对患有严重情绪障碍的患者具有快速抗抑郁作用。 事实上，最近的一项安慰剂对照研究重复了早期的试点研究（Berman 等，2000），并显示单剂量氯胺酮（0.5 mg/kg）对难治性单相抑郁症患者具有强大的急性抗抑郁作用（Zarate et al., 2006），许多患者在几天内保持情绪改善。 为了充分利用静脉注射氯胺酮治疗难治性抑郁症 (TRD) 的前景，本研究将解决两个新问题。 首先，重要的是确定重复剂量静脉注射氯胺酮的有效性，以便可能延长抗抑郁反应，使其超出每次单独给药的急性效果。 其次，确定静脉注射氯胺酮的最大有效剂量和最小厌恶剂量至关重要，该剂量可以安全地重复给药给门诊患者。 患者对药物治疗方案的可接受性是确保静脉注射氯胺酮可能持续获益的关键。最后一个问题涉及氯胺酮治疗（单次给药和重复给药）对大脑活动的影响。我们正在该协议中添加功能成像，以便研究（1）使用功能磁共振成像（fMRI）测量的治疗引起的任务相关 BOLD 反应的变化和（2）使用功能测量的治疗引起的静息态连接的变化连接性 MRI (fcMRI)。 该研究方案将测试 20 名对单剂量静脉注射氯胺酮表现出急性反应的难治性 MDD 患者重复静脉注射氯胺酮的疗效。 将使用单剂量反应来确定用于重复施用的剂量。 主要结果指标是重复给药后抗抑郁药反应后复发的时间。