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年到2017年，美国的自杀率上升了30%以上。去急诊科就诊的个人 (ED)故意自残或自杀念头在一年内的自杀率分别为57倍和31倍 分别大于年龄、性别和种族/民族调整后的一般人口群体。它的目标是 ED作为干预的关键环境以降低自杀风险。然而，美国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。即使这是随机的 包括我们在内的临床试验显示，使用亚麻醉剂治疗后，自杀念头在数小时内得到缓解。 氯胺酮。我们发表的对双相和单相自杀抑郁症患者的对照临床试验发现 氯胺酮在几个小时内减少了自杀念头，这种改善持续了长达六周的时间 优化的、标准的药物治疗。在2017-18年度的两年内，教育署的来访人次超过200万 自杀念头，自我导向的暴力，或者两者兼而有之。患者自杀未遂和自杀的风险更大 在艾德访问之后。一种快速、安全、易用的治疗方法，适用于有严重自杀倾向的急诊室患者 思想或行为会促进公众健康。目前还没有一项关于现成的 用于快速减少ED患者自杀念头的仿制氯胺酮。一项关键的军事建议 战场止痛药是氯胺酮50-100毫克肌肉注射，类似于有效的静脉注射。 用于治疗抑郁症的剂量。静脉注射起效约1分钟，肌注起效约5分钟。我 氯胺酮在成人体内的生物利用度为93%，其血浆半衰期类似于静脉注射。一家诊所 肌注仿制氯胺酮快速减少自杀的可行性、安全性和有效性的试验 ED患者的想法将支持为这一人群提供一种新颖、可扩展、易于使用的治疗方法。我们建议 进行肌注氯胺酮与肌注咪达唑仑(我们先前的氯胺酮试验中使用的活性比较剂)的试验 有严重自杀意念或行为需要住院治疗的ED患者。初级阶段 结果将是可行性、安全性，并在24小时内减少自杀念头。次要结果将是 包括对住院时间、认知功能、自杀念头和行为的影响 出院，众所周知的自杀高危时期。

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