Ketamine for the treatment for opioid use disorder and suicidal ideation in the emergency department

氯胺酮用于治疗急诊科阿片类药物使用障碍和自杀意念

• 批准号: 10646993
• 负责人: Peter R Chai
• 金额: $ 22.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646993
• 关键词: Accident and Emergency department; Acute; Acute Pain; Address; Admission activity; Adverse effects; Agitation; Alcohols; Anesthetics; Animals; Back; Behavior Therapy; Behavioral Mechanisms; Blood Pressure; COVID-19 pandemic; Cardiovascular system; Caring; Cocaine use disorder; Data; Diastolic blood pressure; Disease; Dose; Double-Blind Method; Eligibility Determination; Emergency department crowding; Emergency department visit; Event; Face; Feeling suicidal; Foundations; Goals; Heart Rate; Human; Incidence; Individual; Infusion procedures; Intervention; Intravenous; Ketamine; Link; Mental Depression; Mental disorders; Methods; Monitor; National Institute of Drug Abuse; Opioid; Opioid Receptor; Outcome; Outcome Assessment; Overdose; Pain; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Prevalence; Prevention; Psychiatric therapeutic procedure; Psychotherapy; Public Health; Randomized; Relapse; Reporting; Research; Safety; Saline; Sedation procedure; Serious Adverse Event; Substance Use Disorder; Suicide; Suicide attempt; Symptoms; Tachycardia; Testing; Toxicology; Visit; addiction; alcohol use disorder; antidepressant effect; arm; behavior change; comorbidity; completed suicide; craving; depressive symptoms; design; drug misuse; efficacy trial; emergency settings; experience; follow-up; hemodynamics; hypertensive; improved; improved outcome; innovation; interest; medication for opioid use disorder; opioid overdose; opioid use; opioid use disorder; opioid withdrawal; overdose death; pharmacologic; prevent; primary outcome; randomized placebo controlled trial; randomized trial; safety assessment; safety outcomes; screening; screening, brief intervention, referral, and treatment; secondary outcome; side effect; substance misuse; suicidal; timeline; treatment-resistant depression

Project summary Emergency departments (ED) in the US have experienced a significant increase in admissions for opioid-related overdoses and suicide attempts during the COVID pandemic. Individuals with opioid use disorder (OUD) have a lifetime prevalence of suicide attempts exceeding 40%, along with elevated odds of a completed suicide. Among the 100,000 drug-related overdose deaths in 2021—the largest number ever recorded in a 12-month period— 30% or more of such events may in fact be suicides. In 2017, there were over 960,000 ED visits in the US for a non-fatal overdose, making the ED a critical setting in which to intervene. Behavioral interventions like Screening, Brief Intervention, and Referral to Treatment (SBIRT) in the ED improve alcohol outcomes, but multiple trials have failed to show any benefit of SBIRT for individuals with OUD. Structural barriers like ED crowding and lack of follow up for addiction and psychiatric treatment also mar efforts to treat these diseases. Despite the increased utilization of medications for OUD (MOUD) in the ED setting, most patients still do not receive MOUD in the ED, and among those who do, the majority do not continue treatment after discharge. Therefore, there is a critical need for research to identify treatments that can be delivered effectively and sustainably in the ED for individuals with OUD particularly for those who are endorsing suicidal ideation. Ketamine has garnered interest due to its potential in treating psychiatric disorders, rapidly diminishing depressive and suicidal symptoms among individuals with treatment-resistant depression. Sub-anesthetic doses of ketamine administered in either single or multiple sessions in conjunction with psychotherapy has shown beneficial effects for patients with alcohol, opioid, and cocaine use disorders. A major advantage of ketamine is that it is already an accepted pharmacotherapy used routinely in the ED for procedural sedation, agitation, and acute pain. If ketamine could be used as an effective pharmacotherapy for OUD and suicidal ideation in the ED, the approach would be consistent with Screening, Treatment Initiation, and Referral (STIR) which may be more beneficial than the traditional SBIRT approach. However there remains a significant gap in understanding the safety of ED-initiated ketamine for those with OUD in the ED. To fill this need, we propose to conduct a pilot, double-blind, placebo- controlled randomized trial with the primary aim of assessing the safety of administering ketamine in the ED to OUD patients who are endorsing suicidal ideation. Those who are eligible will be randomly assigned to receive either a single infusion of ketamine or saline placebo. Vital signs, side effects, psychiatric adverse effects, opioid withdrawal, and cravings for opioids and ketamine will be monitored closely throughout the ED admission. As a secondary aim, we will determine the preliminary efficacy of ketamine on opioid- and suicide-related outcomes. Mechanisms of behavior change will be explored. If successful, this line of research will help establish the safety of ketamine administration for OUD in the ED, and facilitate the design of a larger efficacy trial.

项目摘要 美国的急诊科（艾德）因阿片类药物相关疾病而入院的人数显著增加， 在COVID大流行期间过量服用和自杀企图。阿片类药物使用障碍（OUD）的患者 自杀未遂的终生患病率超过40%，沿着自杀未遂的几率升高。之间 2021年有10万人因吸毒过量死亡，这是12个月内有史以来最多的数字， 事实上，30%或更多的此类事件可能是自杀。2017年，美国有超过96万人次的艾德就诊， 非致命性过量，使得艾德成为干预的关键环境。行为干预，如筛查， 艾德中的短期干预和转诊治疗（SBIRT）可改善酒精结局，但多项试验 没有显示SBIRT对OUD患者有任何益处。结构性障碍，如艾德拥挤和缺乏 成瘾和精神病治疗的后续行动也损害了治疗这些疾病的努力。尽管加大 在艾德环境中使用药物治疗OUD（MOUD），大多数患者在艾德中仍然不接受MOUD， 而在接受治疗的病人中，大多数在出院后不再继续接受治疗。因此，有一个关键的 需要进行研究，以确定可以在艾德中有效和可持续地为个人提供的治疗 特别是那些支持自杀想法的人。克他命引起了人们的兴趣， 治疗精神疾病的潜力，迅速减少抑郁和自杀症状， 患有难治性抑郁症的人单次给予亚麻醉剂量的氯胺酮 或多个疗程结合心理治疗对酒精患者显示出有益的效果， 阿片类药物和可卡因使用障碍。氯胺酮的一个主要优点是它已经是一种公认的 在艾德中常规使用的药物疗法，用于程序性镇静、激动和急性疼痛。如果克他命能 作为艾德中OUD和自杀意念的有效药物治疗， 与筛选、治疗启动和转诊（STIR）一致，这可能比 传统的SBIRT方法。然而，在理解ED启动的安全性方面仍存在重大差距。 氯胺酮用于急诊室的OUD患者。为了满足这一需求，我们建议进行一项试验，双盲，安慰剂- 一项随机对照试验，主要目的是评估艾德中氯胺酮给药的安全性， 支持自杀意念的OUD患者。符合条件的人将被随机分配 单次输注氯胺酮或生理盐水安慰剂。生命体征、副作用、精神不良反应、阿片类药物 在艾德住院期间，将密切监测戒断和对阿片类药物和氯胺酮的渴望。作为 次要目的，我们将确定氯胺酮对阿片类药物和自杀相关结局的初步疗效。 将探讨行为改变的机制。如果成功，这一系列的研究将有助于建立安全的 在艾德中，氯胺酮给药治疗OUD，并有助于设计更大的疗效试验。