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.

项目总结/摘要 从1999年到2017年，美国的自杀率上升了30%以上。访问急诊室的个人 (ED)故意自残或有自杀念头的人一年内的自杀率分别是 分别高于年龄、性别和种族/民族调整的一般人群。这是针对 艾德作为干预降低自杀风险的关键设置。美国食品和药物管理局（FDA） 用于快速缓解抑郁症患者自杀念头的获批治疗。即使是随机的 包括我们在内的临床试验显示，使用亚麻醉剂治疗数小时后， 氯胺酮我们在双相和单相自杀性抑郁症患者中发表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， 优化的标准药物疗法在2017-18两年期间，有超过200万次艾德访问 自杀意念自我导向暴力或两者皆有患者自杀未遂和自杀的风险更大 在艾德来访之后。一种快速、安全、易于使用的治疗方法，用于患有严重自杀倾向的艾德患者 思想或行为会促进公共健康。目前还没有一个明确的研究， 非专利氯胺酮用于快速减少艾德患者的自杀念头。一个关键的军事建议， 战场镇痛是氯胺酮50-100 mg肌肉注射（im），类似于有效的静脉注射（iv） 用于抑郁症的剂量。静脉注射约1分钟起效，肌肉注射约5分钟起效。IM 氯胺酮在成年人中的生物利用度为93%，并且其血浆半衰期与静脉给药相似。临床 一项试验证实了肌肉注射氯胺酮快速减少自杀的可行性、安全性和有效性 艾德患者的想法将支持一种新的、可扩展的、易于使用的治疗方法。我们提出 进行一项im氯胺酮与im咪达唑仑（我们既往氯胺酮试验中使用的活性对照药物）的试验， 出现重度自杀意念或行为需要精神科住院治疗的艾德患者。主 结果将是可行性、安全性和24小时内自杀念头的减少。次要结局将 包括对住院时间、认知功能、自杀念头和自杀行为的影响。 出院是自杀的高危期