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: 10469693
• 负责人: Michael F Grunebaum
• 金额: $ 57.59万
• 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 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469693
• 关键词: Absence of pain sensation; Accident and Emergency department; Acute; Adult; Adverse effects; Aftercare; Age; Anesthetics; Antidepressive Agents; 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.

项目摘要/摘要 从1999年至2017年，美国自杀率上升了30％以上。访问急诊室的个人 （ed）故意自我伤害或自杀思想的自杀率在一年内为57倍和31次 分别比年龄，性别和种族/种族调整的普通人群更大。这是针对的 ED作为干预以减少自杀风险的关键环境。但是，没有美国食品药品监督管理局（FDA） 批准的治疗方法可以快速缓解抑郁症患者的自杀思想。这是随机的 临床试验（包括我们的临床试验）在接受亚侵犯治疗后数小时内显示出自杀念头的缓解 氯胺酮。我们在双极和单极自杀抑郁症患者中发表的对照临床试验发现 氯胺酮在几个小时内降低了自杀念头，改善持续了六个星期 优化的标准药物疗法。在2017 - 18年度的两年中，有超过200万的ED访问 为了自杀的想法，自我指导的暴力或两者兼而有之。患者有自杀企图和自杀的风险更大 埃德访问后。对出现严重自杀的ED的患者的快速，安全且易于使用的治疗 思想或行为将提高公共卫生。尚未有一项明确的研究 通用氯胺酮用于快速减少ED患者自杀思想的速度。一个关键的军事建议 战场镇痛是氯胺酮50-100毫克肌肉内（IM）注射，类似于有效的静脉内（IV） 用于抑郁的剂量。临床效应的发作约为1分钟，IV和IM注射5分钟。我是 氯胺酮在成年人中的生物利用度为93％，血浆半衰期类似于静脉注射。临床 试验证明了IM的可行性，安全性和有效性，通用氯胺酮快速降低自杀 ED患者的想法将为该人群提供一种新颖，可扩展，易于使用的治疗。我们建议 在进行IM氯胺酮与IMInazolam的试验（我们先前的氯胺酮试验中使用的主动比较器） ED患者表现出严重的自杀想法或需要精神病住院的行为。主要 结果将在24小时内可行，安全性和自杀想法的可行性，安全性和降低。次要结果将 包括对住院时间长度，认知功能以及自杀的思想和行为的影响 医院出院，自杀的已知高风险时期。

项目成果

Intramuscular ketamine vs. midazolam for rapid risk-reduction in suicidal, depressed emergency patients: Clinical trial design and rationale.

肌内注射氯胺酮与咪达唑仑可快速降低自杀、抑郁紧急患者的风险：临床试验设计和原理。

• DOI: 10.1016/j.jadr.2023.100690
• 发表时间: 2024
• 期刊: Journal of affective disorders reports
• 作者: Sajid,Sumra;Lawrence,RyanE;Galfalvy,HangaC;Keilp,JohnG;Moitra,VivekK;Mann,JJohn;Grunebaum,MichaelF
• 通讯作者: Grunebaum,MichaelF