OPTIMIZATION OF IV KETAMINE FOR TREATMENT RESISTANT MAJOR DEPRESSION

优化静脉注射氯胺酮治疗难治性重度抑郁症

• 批准号: 7953740
• 负责人: SANJAY J MATHEW
• 金额: $ 0.02万
• 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/7953740
• 关键词: Adult; Adverse effects; Adverse event; Affinity; Anesthesia procedures; Anesthetics; Antidepressive Agents; Childhood; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Dose; Double-Blind Method; Effectiveness; Excitatory Amino Acid Antagonists; Failure; Funding; Grant; Hour; Infusion procedures; Institution; Intervention; Intervention Studies; Intravenous; Intravenous Anesthetics; Intravenous infusion procedures; Ketamine; Major Depressive Disorder; Midazolam; Mood Disorders; Moods; Morbidity - disease rate; N-Methylaspartate; Operative Surgical Procedures; Pain management; Participant; Patients; Placebos; Property; Protocols documentation; Publishing; Randomized; Relapse; Research; Research Personnel; Resistance; Resources; Role; Safety; Saline; Source; Testing; United States National Institutes of Health; active control; blind; depression; depressive symptoms; discontinuation trial; 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. Hypothesis: 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 N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard intravenous (IV) anesthetic agent for many years in both pediatric and adult patients, with IV doses of 2 mg kg-1 producing surgical anesthesia within 30 seconds and lasting 5-10 minutes. 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. Two published studies have now shown that a single 0.5 mg kg-1 dose of ketamine in patients with treatment-resistant MDD causes a robust antidepressant effect within 2 hours, and many patients subsequently maintain a mood improvement for several days (though all had undergone relapse within 2 weeks). However, ketamine s effectiveness in treating depression is still considered a preliminary finding, especially given that the two studies described previously used an inactive placebo (IV saline) in a within-group RCT, in which it was difficult to maintain the blind. Crossing participants over from one treatment to another was problematic in those who had received ketamine on the first infusion day. In the present study we instead propose the use of an active control (IV midazolam) in a between-groups RCT. This will provide much-needed additional evidence that ketamine is indeed effective in treating depression. This research protocol will, in patients with TRD under double-blind conditions, test the antidepressant efficacy of IV ketamine administration in comparison with that of IV midazolam administration. Thus, the study aims: SPECIFIC AIM 1: To test whether a single infusion of IV ketamine exerts superior antidepressant effects compared to an active control agent (IV midazolam) in patients with TRD. Hypothesis 1a: TRD patients randomized to IV ketamine show greater improvement in depressive symptoms compared to patients randomized to IV midazolam, as determined by the change in the MADRS score 24 hours following infusion. Hypothesis 1b: TRD patients randomized to IV ketamine have a higher response rate compared to patients randomized to IV midazolam at 24 hours. SPECIFIC AIM 2: To characterize the durability of antidepressant benefit and test whether treatment with IV ketamine is associated with superior antidepressant effects over the subsequent 7-day interval. Hypothesis 2: TRD patients randomized to ketamine will demonstrate greater durability of antidepressant response than patients randomized to midazolam. SPECIFIC AIM 3: To examine the safety and tolerability of the interventions. Hypothesis 3: Moderate or severe side effects or adverse events will be infrequent or absent. The study interventions will not be associated with distinctly different rates of side effects or adverse events requiring discontinuation from the study.

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。 假设： 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N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂，多年来已用作标准的静脉内（IV）麻醉剂（IV）麻醉剂（IV）麻醉剂，在30秒和最后的5-10分钟内，IV剂量为2 mg kg-kg-1，生产2 mg kg-kg-1的剂量为2 mg kg-kg-kg-1，生产2 mg kg-kg-1。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。现在，两项已发表的研究表明，具有耐药性MDD患者的单一0.5 mg kg-1氯胺酮在2小时内会引起强大的抗抑郁作用，随后许多患者在几天内维持情绪改善（尽管所有患者都在2周内经过了复发性的复发）。然而，氯胺酮在治疗抑郁症方面的有效性仍然被认为是初步发现，尤其是考虑到先前描述的两项研究在集团内RCT中使用了不活跃的安慰剂（IV盐水），在该RCT中很难维持盲人。在第一个输液日接受氯胺酮的人来说，将参与者从一种治疗中跨越到另一种治疗是有问题的。在本研究中，我们建议在组间RCT中使用主动控制（IV咪达唑仑）。这将提供急需的其他证据，表明氯胺酮确实可以有效治疗抑郁症。 该研究方案将在双盲条件下具有TRD的患者，与IV咪达唑仑给药相比，测试IV氯胺酮给药的抗抑郁药疗效。因此，该研究的目的是： 具体目的1：测试与主动对照剂（IV咪达唑仑）对TRD患者的单一输注IV氯胺酮是否具有优势抗抑郁作用。 假设1A：与随机分配给IV咪达唑仑的患者相比，随机分配给IV氯胺酮的TRD患者在抑郁症状上显示出更大的改善，这取决于输注后24小时的MADRS得分的变化确定。 假设1B：与随机在24小时内与IV咪唑仑随机分配给IV的患者相比，随机分配给IV氯胺酮的TRD患者的缓解率更高。 具体目的2：表征抗抑郁药益处的耐用性并测试IV氯胺酮的治疗是否与随后的7天间隔相比，是否与出色的抗抑郁作用有关。 假设2：与随机分配给咪达唑仑的患者相比，随机分配给氯胺酮的TRD患者将表现出抗抑郁反应的耐用性。 特定目的3：检查干预措施的安全性和耐受性。 假设3：中度或严重的副作用或不良事件将很少或不存在。研究干预措施将与副作用率明显不同，或者需要终止研究的不利事件。