Double-Blind Randomized Controlled Trial of Acute-Course of Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents

项目总结 在过去的十年里，年轻人的自杀率急剧上升，现在自杀率排在第二位 15-24岁人群的主要死因。目前还没有有效的治疗方法来降低糖尿病的风险 青少年自杀行为，目前可用的标准治疗效果不大，通常采取 几周或几个月才能生效。因此，迫切需要确定快速有效的治疗方法， 改善与自杀有关的症状，防止自杀事件再次发生。根据以下证据 氯胺酮在减少成人自杀症状方面的有效性，以及一项关于 对于青少年来说，氯胺酮似乎是一种有希望的治疗方法，用于最近发生自杀事件的年轻人。 我们建议在最近有自杀行为的年轻人中进行氯胺酮的第一个随机对照试验。 所有青少年都将在针对自杀青少年的强化门诊计划中接受治疗，并将 随机接受氯胺酮0.5 mg/kg或咪达唑仑0.02 mg/kg静脉滴注，为期两周，共4次 在开始眼压后十天内。我们还将使用死亡/自杀来检验内隐认知关联 内隐联想测验(IAT)所有参与者将被跟踪12周以评估：1)减少重复 超过12周的自杀企图，2)在2周的研究治疗中减少内隐自杀认知 3)在两周的研究期内抑郁和自杀意念的减少。我们还将 探讨IAT的减少是否会在12周内促进自杀倾向的改善。到目前为止，还没有研究表明 报告的证据表明：1)在成人或青少年中使用氯胺酮可减少反复自杀事件(目标1)； 2)青少年的内隐认知(AIM 2)或自杀相关症状(AIM 3)的减少， (3)氯胺酮对自杀的影响的潜在机制。创新特色 包括：1)它针对高危青少年在高危时期重复自杀事件，这些青少年通常 排除在临床试验之外；2)跨诊断；3)无缝集成到当前的护理标准中；以及4) 评估可以在临床需求最大的时间和地点提供的干预措施，但 目前还没有开发出干预措施。

PROJECT SUMMARY Rates of suicide have increased dramatically in youths over the past decade, and suicide is now the 2nd leading cause of death for individuals ages 15-24. There are no validated treatments to decrease the risk of adolescent suicidal behavior, and currently available standard treatments are of modest benefit and often take weeks or months to become effective. Hence, there is an urgent need to identify rapid-acting treatments that ameliorate symptoms associated with suicidality and prevent repeat suicidal events. Based on evidence for efficacy of ketamine in reducing symptoms of suicidality in adults, as well as an open label study in adolescents, ketamine appears to be a promising treatment approach for youths with a recent suicidal event. We propose to conduct the first randomized, controlled trial of ketamine in youth with recent suicidal behaviors. All youth will be in treatment in an intensive outpatient program for suicidal adolescents, and will be randomized to intravenous ketamine 0.5mg/kg or midazolam 0.02mg/kg for four infusions over two weeks within +/- ten days of starting IOP. We will also examine implicit cognitive associations using the Death/Suicide Implicit Association Test (IAT). All participants will be followed for 12 weeks to evaluate: 1) reduction in repeat suicide attempts over 12 weeks, 2) reduction in implicit suicidal cognition within the 2-week study treatment period, and 3) reduction in depression and suicidal ideation within the 2-week study period. We will also explore whether reductions in IAT mediates improvement in suicidality over 12 weeks. To date, no study has reported evidence for 1) reduction in repeat suicidal events with ketamine either in adults or in youths (AIM 1), 2) reductions either in implicit cognition (AIM 2) or in symptoms associated with suicidality (AIM 3) in youths, and 3) underlying mechanisms that mediate (AIM 4) the effects of ketamine on suicidality. Innovative features include: 1) it targets repeat suicidal events during a high-risk period in high-risk youths who are typically excluded from clinical trials; 2) is transdiagnostic; 3) seamlessly integrates in current standard of care; and 4) evaluates an intervention that can be delivered at a time and place when there is greatest clinical need, but for which there are no currently developed interventions.