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

项目总结 美国急诊科(ED)与阿片类药物相关的入院人数显著增加 COVID大流行期间的服药过量和自杀未遂。阿片类药物使用障碍(OUD)患者有 自杀未遂的终生患病率超过40%，同时完全自杀的几率也较高。其中 2021年与药物有关的10万人过量死亡--这是12个月来有记录以来的最大数字-- 30%或更多的此类事件实际上可能是自杀。2017年，美国有超过96万人次的急诊科就诊 非致命的过量用药，使ED成为干预的关键环境。行为干预，比如筛查， 勃起功能障碍的短暂干预和转诊治疗(SBIRT)可改善酒精结局，但有多项试验 未能显示SBIRT对OUD患者有任何好处。结构性障碍，如教育拥挤和缺乏 对成瘾和精神治疗的后续行动也损害了治疗这些疾病的努力。尽管增加了 在急诊室中，大多数患者仍然没有在急诊室接受Moud治疗， 而在那些这样做的人中，大多数人在出院后没有继续治疗。因此，有一个关键的 需要研究以确定可在急诊室有效和可持续地为个人提供的治疗 尤其是对于那些支持自杀想法的人。氯胺酮引起了人们的兴趣，因为它 治疗精神障碍的潜力，迅速减少抑郁和自杀症状 患有难治性抑郁症的个体。亚麻醉剂量的氯胺酮 或多次联合心理治疗对酗酒患者产生了有益的效果， 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被接受 急诊室常规使用药物治疗程序性镇静、激动和急性疼痛。如果氯胺酮能 作为治疗精神分裂症及自杀意念的有效药物，方法如下： 与筛查、治疗启动和转诊(STIR)相一致，这可能比 传统的SBIRT方法。然而，在对ED启动的安全性的理解上仍然存在着很大的差距 氯胺酮适用于在急诊室有OUD的人。为了满足这一需求，我们建议进行一项双盲安慰剂试验- 随机对照试验，主要目的是评估氯胺酮在ED中的安全性 支持自杀念头的患者。符合条件的人将被随机分配到 不是一次输注氯胺酮就是生理盐水安慰剂。生命体征、副作用、精神不良反应、阿片类药物 在ED入院期间，将密切监测戒断、对阿片类药物和氯胺酮的渴望。作为一名 其次，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。 我们将探索行为改变的机制。如果成功，这一系列研究将有助于建立安全 在急诊室使用氯胺酮，并促进设计一项更大的疗效试验。

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.