Ketamine for the treatment for alcohol use disorder in the emergency department: A pilot double-blind, placebo-controlled randomized clinical trial

项目摘要摘要 据估计，有1500万美国人患有酒精使用障碍(AUD)，每年导致9.5万人死于 与酒精有关的原因和2500亿美元的经济负担。然而，流行病学研究一直以来 研究发现，绝大多数澳门氏症患者没有接受任何循证治疗。其中一个 未经治疗的AUD的后果是需要医疗来解决急性和慢性影响 酗酒导致与酒精相关的急诊科就诊人数 从310万增加到500万，增幅为61.6%。这使得教育署成为一个重要和及时的参与环境 AUD患者进入成瘾治疗，如行为干预的成功证明 筛查、短期干预和转诊治疗(SBIRT)。然而，SBIRT对 那些患有严重澳门氏症的人，许多急救人员很难成功地实施和维持Brief 干预措施。因此，可以在ED环境中实施的更有效的策略是解决AUD 这是急需的。氯胺酮已成为AUD的一种潜在治疗选择。氯胺酮已经获得了 由于其在治疗精神障碍、迅速减轻抑郁和自杀症状方面的潜力而引起人们的兴趣 在患有难治性抑郁症的个体中。亚麻醉剂量的氯胺酮 单次或多次与心理治疗相结合的治疗对患有 酒精、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 作为急诊室AUD的有效药物治疗，该方法将与筛查一致， 治疗开始和转诊(STIR)，这对严重的AUD患者可能比 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 氯胺酮在改善寻求戒毒者的AUD相关结果方面的作用。为满足这方面的需要，我们建议 进行一项试点双盲安慰剂对照随机临床试验，主要目的是评估 急诊室使用氯胺酮对寻求入院戒毒室的澳大利亚人的安全性。 所有参与者都将接受医院的标准戒毒治疗，其中还包括强化戒毒 心理社会支持。参与者的选择将侧重于确保排除那些有潜在医疗风险的人 以及精神合并症，这在用药氯胺酮时会带来风险。符合条件的参与者将随机选择 被分配到急诊室接受一次氯胺酮或生理盐水安慰剂输注。生命体征，不良反应， 在整个试验过程中，将密切监测戒酒和对酒精和氯胺酮的渴望。作为一种 探索性目的，我们将评估与酒精相关的结果以及行为改变的机制。如果 如果成功，这项研究将有助于确定在急诊室使用氯胺酮治疗AUD的安全性，以及 促进设计一项动力充足的疗效试验。

Project Summary Abstract An estimated 15 million Americans have an alcohol use disorder (AUD), resulting annually in 95,000 deaths from alcohol-related causes and 250 billion dollars in economic burden. Yet, epidemiologic studies have consistently found that the vast majority of those with AUD are not receiving any evidence-based treatments. One of the consequences of an untreated AUD is the need for medical treatment to address the acute and chronic effects of heavy drinking, which has resulted in the number of alcohol-related emergency department (ED) visits to increase by 61.6% from 3.1 million to 5.0 million. This makes the ED an important and timely setting to engage individuals with AUD to enter addiction treatment as evidenced by the success of behavioral interventions like Screening, Brief Intervention and Referral to Treatment (SBIRT). However, SBIRT has not been as impactful for those with severe AUD, and it has been difficult for many EDs to successfully implement and sustain brief interventions. As such, more effective strategies that can be implemented in the ED setting to address AUD are critically needed. Ketamine has emerged as a potential treatment option for AUD. 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 AUD in the ED, the approach would be consistent with Screening, Treatment Initiation, and Referral (STIR) which may be more beneficial for patients with severe AUD than the traditional SBIRT approach. However there remains a significant gap in understanding the safety of ED-initiated ketamine in improving AUD-related outcomes for those who seek detoxification. To fill this need, we propose to conduct a pilot double-blind placebo-controlled randomized clinical trial with the primary aim of assessing the safety of administering ketamine in the ED to AUD patients seeking admission to an inpatient detoxification unit. All participants will receive the hospital’s standard detoxification treatment which also includes intensive psychosocial support. Participant selection will focus on ensuring the exclusion of those with potential medical and psychiatric co-morbidities that pose a risk when administered ketamine. Eligible participants will be randomly assigned to receive either a single infusion of ketamine or saline placebo in the ED. Vital signs, adverse effects, alcohol withdrawal, and craving for alcohol and ketamine will be monitored closely throughout the trial. As an exploratory aim, we will assess alcohol-related outcomes as well as mechanisms of behavior change. If successful, this line of research will help establish the safety of ketamine administration for AUD in the ED, and facilitate the design of an adequately powered efficacy trial.