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

基本信息

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
项目类别：
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

项目摘要

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.

描述（由申请人提供）：在美国，自杀和自杀未遂每年造成的损失估计为 330 亿美元，造成的痛苦和折磨难以估量。大多数自杀行为与抑郁症有关，但针对自杀患者的药物指南几乎不存在。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会持续几天，然而，抑郁和自杀倾向通常是慢性、反复出现的状况。我们建议在自杀性抑郁症患者中进行严格的临床试验，以测试随机分配氯胺酮或咪达唑仑静脉输注对照，然后使用抗抑郁药物和支持性病例管理进行开放式持续治疗。主要目标是测试氯胺酮与类似的镇静控制药物（未知是否可以减少自杀意念）相比的潜在抗自杀作用。探索性目标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。在这一高危人群中建立氯胺酮的强烈抗自杀信号将支持创新干预措施，从而改变对具有公共卫生重要性的患者群体的临床护理。对继续治疗期间的自杀意念和行为进行探索性评估有助于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 30,000 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，抑郁症患者在单次低剂量静脉输注氯胺酮后数小时内自杀意念迅速改善。我们建议进行一项严格的试验，以测试氯胺酮在改善具有临床显着自杀意念的抑郁症患者的自杀意念方面的功效，这些患者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。