Ketamine vs Midazolam: Testing Rapid Relief of Suicide Risk in Depression

描述(申请人提供)：在美国，自杀和自杀企图每年造成约330亿美元的损失，以及无法估量的痛苦和痛苦。大多数自杀行为与抑郁障碍有关，但针对自杀患者的用药指南几乎是不存在的。证据基础严重有限，因为自杀患者被排除在大多数抗抑郁药物临床试验之外。最近的几项研究表明，抑郁症患者在静脉注射后，自杀意念在短短一小时内迅速改善。 输注亚麻醉剂氯胺酮，一种谷氨酸拮抗剂和常用麻醉剂。自杀意念的改善似乎持续了几天，然而，抑郁和自杀通常是慢性的、反复出现的情况。我们建议在自杀抑郁患者中进行一项严格的临床试验，以测试随机分配到静脉输注氯胺酮或咪达唑仑对照，然后开放持续治疗抗抑郁药物和支持性病例处理。主要目的是测试氯胺酮与一种类似的镇静控制药物相比的潜在抗自杀效果，这种药物并不能减少自杀念头。探索性目标还包括分析潜在的生物学(唾液皮质醇)和神经认知相关因素。 作为对持续治疗期间自杀意念和行为的系统评估。在这一高危人群中建立一个强大的氯胺酮反自杀信号将支持一种创新的干预措施，这可能会改变对公共健康具有重要意义的患者群体的临床护理。对持续治疗期间自杀意念和行为的探索性评估可以帮助有针对性地研究维持氯胺酮益处的策略。 公共卫生相关性：自杀是美国第十大死因，每年导致超过3万人死亡，但令人惊讶的是，缺乏针对自杀性抑郁症的循证治疗。研究表明，在单次小剂量静脉输注氯胺酮后，抑郁症患者的自杀意念在几个小时内迅速改善。我们建议进行一项严格的试验，以测试氯胺酮对有临床意义自杀意念的抑郁症患者改善自杀意念的有效性，自杀意念是公共卫生目标的关键人群，但通常被排除在临床试验之外。

DESCRIPTION (provided by applicant): Suicide and suicide attempts cost an estimated $33 billion annually in the U.S. and immeasurable pain and suffering. Most suicidal behavior is associated with a depressive disorder, yet medication guidelines for suicidal patients are virtually nonexistent. The evidence base is severely limited because suicidal patients are excluded from most antidepressant clinical trials. Several recent studies show rapid improvement in suicidal ideation, in as little as one hour, in depressed patients after intravenous infusion of sub-anesthetic ketamine, a glutamate antagonist and commonly used anesthetic. The improvement in suicidal ideation appears to last several days, however, depression and suicidality are usually chronic, recurring conditions. We propose a rigorous clinical trial in suicidal depressed patients to test random assignment to IV infusion of ketamine or midazolam control followed by open continuation treatment with antidepressant medication plus supportive case management. The primary goal is to test ketamine's potential anti-suicidal effects versus a similarly sedative control medication not known to reduce suicidal ideation. Exploratory aims include analysis of potential biological (salivary cortisol) and neuro-cognitive correlates as well as systematic assessment of suicidal ideation and behavior during continuation treatment. Establishing a strong anti-suicidal signal for ketamine in this high-risk population would support an innovative intervention that could change clinical care for a patient population of public healt importance. Exploratory assessment of suicidal ideation and behavior during continuation treatment could help target research on strategies to sustain the benefit of ketamine. PUBLIC HEALTH RELEVANCE: Suicide is the 10th leading cause of death in the U.S. resulting in more than 30,000 deaths annually, but there is a surprising lack of evidence-based treatment for suicidal depression. Studies suggest rapid improvement in suicidal ideation in depressed patients within hours after a single, low-dose intravenous infusion of ketamine. We propose a rigorous trial to test the efficacy of ketamine in improving suicidal ideation in depressed patients with clinically significant suicidal ideation, a key population for the public health goal of suicide prevention, but which is usually excluded from clinical trials.