CONTINUOUS INTRAVENOUS KETAMINE IN MAJOR DEPRESSIVE DISORDER

重度抑郁症持续静脉注射氯胺酮

• 批准号: 7953711
• 负责人: Dennis S. Charney
• 金额: $ 1.05万
• 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/7953711
• 关键词: Acute; Address; Adult; Affinity; Anesthesia procedures; Anesthetics; Antidepressive Agents; Brain; Childhood; Clinical Research; 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; Intravenous Anesthetics; Investigation; Ketamine; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; 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; Therapeutic; Time; Treatment Protocols; Unipolar Depression; United States National Institutes of Health; blood oxygenation level dependent response; depression; depressive symptoms; efficacy testing; 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. 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。 现有的重大抑郁症（MDD）治疗通常需要数周到几个月才能发挥最大收益。 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的静脉内（IV）麻醉剂，剂量高达2 mg/kg。 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，最近进行的一项安慰剂对照研究复制了一项早期的试点研究（Berman等，2000），并显示了一种氯胺酮（0.5 mg/kg）的急性急性抗抑郁作用，对具有治疗的单极抑郁症患者（Zarate等人，2006年），许多患者维持了几天的情绪，对耐药治疗的单极抑郁症（Zarate等人，2006年）表现出了强大的急性抗抑郁作用。 为了充分利用IV氯胺酮治疗耐药性抑郁症（TRD）的治疗承诺，本研究将解决两个新问题。 首先，重要的是要确定重复剂量的静脉氯胺酮的有效性，以便可能延长抗抑郁反应以外的抗抑郁反应。 其次，至关重要的是要识别最大有效的同时，而在重复剂量上可以安全地施用对门诊病人的静脉注射型氯胺酮。 药物方案的患者可接受性是确保IV氯胺酮可能持续益处的关键。最后一个问题与氯胺酮治疗（单一和重复给药）对脑活动的影响有关。我们正在为该协议添加功能成像，以研究（1）使用功能磁共振成像（fMRI）和（2）治疗诱导的使用功能连接性MRI（FCMRI）测量的静息状态连接的变化测得的与任务相关的BOLD响应的变化。 该研究方案将测试反复静脉注射氯胺酮对20例耐药MDD患者的疗效，这些患者对单剂量的静脉注射氯胺酮表现出急性反应。 用于重复给药的剂量将使用单剂量反应确定。 主要结果度量是在抗抑郁药对重复给药后反应后复发的时候了。