IM Ketamine for rapid reduction of suicidal thoughts in high-risk emergency room patients: a midazolam-controlled trial

肌内注射氯胺酮可快速减少高危急诊室患者的自杀念头：一项咪达唑仑对照试验

• 批准号: 10264940
• 负责人: Michael F Grunebaum
• 金额: $ 57.57万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10264940
• 关键词: Absence of pain sensation; Accident and Emergency department; Acute; Adult; Adverse effects; Aftercare; Age; Anesthetics; Antidepressive Agents; Bioavailable; Bipolar Depression; Bladder; Brain; Chronic; Clinical Trials; Controlled Clinical Trials; DSM-V; Depressed mood; Dissociative Anesthetics; Dose; Double-Blind Method; Drug Costs; Effectiveness; Emergency Department patient; Emergency Situation; Emergency department visit; Ethnic Origin; Evaluation; Excitatory Amino Acid Antagonists; Exclusion; Feeling suicidal; Fluoxetine; Frequencies; General Population; Glutamates; Half-Life; Hospitalization; Hospitals; Hour; Individual; Inpatients; Insurance; Intellectual functioning disability; Intervention; Intramuscular; Intramuscular Injections; Intravenous; Intravenous infusion procedures; Ketamine; Length of Stay; Logistics; Maintenance; Manic; Measures; Mediating; Medical; Mental Depression; Midazolam; Military Personnel; N-Methylaspartate; Neurotransmitters; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Plasma; Population; Population Group; Psychiatry; Psychoses; Public Health; Publishing; Race; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recommendation; Reporting; Research; Risk; Safety; Self-Direction; Self-Injurious Behavior; Severities; Site; Structure; Substance Use Disorder; Suicide; Suicide attempt; Suicide prevention; Therapeutic; Time; Toxic effect; United States Food and Drug Administration; Violence; Work; active comparator; antidepressant effect; biological sex; clinical effect; clinically significant; cognitive control; cognitive function; depressed patient; enantiomer; follow-up; high risk; human old age (65+); improved; instrument; monoamine; novel; primary outcome; psychiatric emergency; reducing suicide; secondary outcome; sex; side effect; suicidal; suicidal behavior; suicidal risk; suicide rate; treatment-resistant depression; venlafaxine

Project Summary/Abstract US suicide rates rose more than 30% from 1999 – 2017. Individuals who visit an emergency department (ED) for deliberate self-harm or suicidal thoughts have suicide rates within a year that are 57 and 31 times greater, respectively, than age-, sex-, and race/ethnicity-adjusted general population groups. This targets the ED as a key setting to intervene to reduce suicide risk. Yet, there is no U.S. Food and Drug Administration (FDA) approved treatment for rapid relief of suicidal thoughts in depressed patients. This is even though randomized clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with sub-anesthetic ketamine. Our published, controlled clinical trials in bipolar and unipolar suicidal depressed patients found that ketamine reduced suicidal thoughts within hours and the improvement persisted for up to six weeks with optimized, standard pharmacotherapy. During the two years 2017-18 there were more than 2 million ED visits for suicidal ideation, self-directed violence, or both. Patients are at greater risk for suicide attempts and suicide after an ED visit. A rapid, safe, and easy-to-use treatment for patients presenting to an ED with severe suicidal thoughts or behavior would advance public health. There has not yet been a definitive study of readily available generic ketamine for rapid reduction of suicidal thoughts in ED patients. A key military recommendation for battlefield analgesia is ketamine 50-100 mg intramuscular (im) injection, similar to effective intravenous (iv) doses used for depression. Onset of clinical effects is about 1 minute with iv and 5 minutes with im injection. IM ketamine is 93% bioavailable in adult humans and has a plasma half-life similar to iv administration. A clinical trial demonstrating feasibility, safety, and effectiveness of im, generic ketamine for rapid reduction of suicidal thoughts in ED patients would support a novel, scalable, easy-to-use treatment for this population. We propose to conduct a trial of im ketamine versus im midazolam (an active comparator used in our prior ketamine trials) in ED patients presenting with severe suicidal ideation or behavior requiring psychiatric hospitalization. The primary outcomes will be feasibility, safety, and reduction of suicidal thoughts within 24 hours. Secondary outcomes will include effects on length of stay, cognitive function, and suicidal thoughts and behavior during the month after hospital discharge, a known high-risk period for suicide.

项目概要/摘要 1999 年至 2017 年间，美国自杀率上升了 30% 以上。 到急诊室就诊的个人 (ED) 因小心自残或有自杀念头而一年内自杀率分别为 57 倍和 31 倍 分别高于按年龄、性别和种族/族裔调整的一般人口群体。 急诊室是干预降低自杀风险的关键场所，但美国却没有食品和药物管理局 (FDA)。 批准用于快速缓解抑郁症患者自杀念头的治疗方法尽管是随机的。 包括我们在内的临床试验表明，在亚麻醉治疗后数小时内，自杀念头就会得到缓解 我们发表的针对双相和单相自杀抑郁症患者的对照临床试验发现， 氯胺酮在数小时内减少了自杀念头，并且这种改善持续了长达六周 2017-18 两年间，急诊就诊人数超过 200 万人次。 自杀意念、自我暴力或两者兼而有之，患者自杀未遂和自杀的风险更大。 急诊科就诊后为患有严重自杀倾向的患者提供快速、安全且易于使用的治疗方法。 思想或行为是否会促进公共健康目前还没有明确的研究。 用于快速减少 ED 患者自杀念头的通用氯胺酮是针对 ED 患者的一项重要军事建议。 战地镇痛为氯胺酮50-100毫克肌内（im）注射，与有效静脉注射（iv）相似 用于治疗抑郁症的剂量，静脉注射约 1 分钟，肌内注射约 5 分钟。 氯胺酮在成年人中的生物利用度为 93%，血浆半衰期与临床静脉注射相似。 试验证明肌内注射（非专利氯胺酮）快速减少自杀倾向的可行性、安全性和有效性 我们对 ED 患者的想法支持为该人群提供一种新颖的、可扩展的、易于使用的治疗方法。 进行伊姆氯胺酮与伊姆咪达唑仑（我们之前的氯胺酮试验中使用的活性比较剂）的试验 出现严重自杀意念或行为的 ED 患者需要住院治疗。 次要结果将是可行性、安全性以及 24 小时内自杀念头的减少。 包括对住院时间、认知功能以及术后一个月自杀想法和行为的影响 出院，这是已知的自杀高危期。