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

氯胺酮与咪达唑仑：测试快速缓解抑郁症自杀风险

• 批准号: 8400023
• 负责人: Michael F Grunebaum
• 金额: $ 58.41万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-05 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8400023
• 关键词: Accident and Emergency department; Adrenal Glands; Adverse effects; Adverse event; Anesthetics; Antidepressive Agents; Benzodiazepines; Biological; Bupropion; Case Management; Cause of Death; Cessation of life; Chronic; Clinical Treatment; Clinical Trials; Cognitive; Data; Depressed mood; Depression and Suicide; Depressive disorder; Dose; Double-Blind Method; Eligibility Determination; Evidence based treatment; Excitatory Amino Acid Antagonists; Feeling suicidal; Glutamates; Goals; Guidelines; Hamilton Rating Scale for Depression; Hour; Hydrocortisone; Hyperactive behavior; Hypothalamic structure; Impaired cognition; Infusion procedures; Intervention; Intravenous infusion procedures; Ketamine; Major Depressive Disorder; Measures; Memory; Mental Depression; Midazolam; Moods; Neurocognitive; Pain; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Pituitary Gland; Placebos; Population; Public Health; Randomized; Recruitment Activity; Relative (related person); Reporting; Research; Safety; Saline; Salivary; Sampling; Selective Serotonin Reuptake Inhibitor; Signal Transduction; Suicide; Suicide attempt; Suicide prevention; System; Targeted Research; Testing; Time; blind; clinical care; clinically relevant; clinically significant; cost; efficacy testing; evidence base; high risk; hypothalamic-pituitary-adrenal axis; improved; innovation; interest; patient population; psychosocial; response; sedative; single episode major depressive disorder; suicidal; suicidal behavior; suicidal patient; suicidal risk; suicide attempter; treatment effect

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.

在美国，自杀和自杀企图每年造成的损失估计为330亿美元，带来的痛苦和痛苦是不可估量的。大多数自杀行为都与抑郁症有关，但自杀患者的药物指南实际上是不存在的。由于大多数抗抑郁药临床试验都排除了有自杀倾向的患者，因此证据基础非常有限。最近的几项研究表明，抑郁症患者在接受静脉注射后，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，抑郁症和自杀倾向通常是慢性的，反复发作的疾病。我们建议在自杀性抑郁症患者中进行一项严格的临床试验，以测试随机分配至氯胺酮或咪达唑仑对照静脉输注，然后开放式持续抗抑郁药物治疗加支持性病例管理。主要目标是测试氯胺酮与类似的镇静对照药物相比的潜在抗自杀作用，目前尚不清楚该药物是否能减少自杀念头。探索性的目的包括分析潜在的生物学（唾液皮质醇）和神经认知相关性 作为持续治疗期间自杀意念和行为的系统评估。在这一高风险人群中建立氯胺酮的强有力的抗自杀信号将支持一种创新的干预措施，这种干预措施可能会改变对公共卫生具有重要意义的患者群体的临床护理。在继续治疗期间对自杀意念和行为进行探索性评估，有助于对维持氯胺酮获益的策略进行靶向研究。 公共卫生相关性：自杀是美国第十大死亡原因，每年导致3万多人死亡，但令人惊讶的是，自杀性抑郁症缺乏循证治疗。研究表明，在单次低剂量氯胺酮静脉输注后数小时内，抑郁症患者的自杀意念迅速改善。我们提出了一项严格的试验，以测试氯胺酮在改善具有临床意义的自杀意念的抑郁症患者的自杀意念方面的疗效，这是预防自杀的公共卫生目标的关键人群，但通常被排除在临床试验之外。