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

氯胺酮在急诊科治疗酒精使用障碍：一项双盲、安慰剂对照随机临床试验

• 批准号: 10593244
• 负责人: Peter R Chai
• 金额: $ 25.73万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-12 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593244
• 关键词: Abstinence; Accident and Emergency department; Acute; Acute Pain; Address; Admission activity; Adverse effects; Aftercare; Agitation; Alcohol consumption; Alcohol withdrawal syndrome; Alcohols; American; Anesthetics; Back; Behavior Therapy; Behavioral Mechanisms; Benzodiazepines; Biological Markers; Blood Pressure; Caring; Chronic; Cocaine use disorder; Country; Diastolic blood pressure; Dissociative Anesthetics; Dose; Double-Blind Method; Drug Metabolic Detoxication; Economic Burden; Emergency Medicine; Emergency department visit; Ensure; Evidence based treatment; Exclusion; Foundations; Funding; Goals; Heart Rate; Heavy Drinking; Hospitals; Incidence; Individual; Infusion procedures; Inpatients; Intervention; Intravenous; Ketamine; Medical; Mental disorders; Monitor; N-Methylaspartate; National Institute on Alcohol Abuse and Alcoholism; Outcome; Participant; Patients; Pharmacotherapy; Placebo Control; Placebos; Positioning Attribute; Property; Psychiatrist; Psychosocial Assessment and Care; Psychotherapy; Public Health; Randomized; Relapse; Reporting; Research; Research Personnel; Research Project Grants; Risk; Safety; Saline; Sedation procedure; Serious Adverse Event; Serum; Symptoms; Tachycardia; Time; United States National Institutes of Health; Urine; Withdrawal; addiction; adverse drug reaction; alcohol abuse therapy; alcohol craving; alcohol use disorder; alcohol-related death; antagonist; base; behavior change; brief intervention; craving; depressive symptoms; design; drinking; efficacy evaluation; efficacy trial; eligible participant; epidemiology study; experience; follow-up; hypertensive; implementation strategy; improved; innovation; interest; opioid use; phosphatidylethanol; primary outcome; psychiatric comorbidity; randomized placebo-controlled clinical trial; randomized trial; screening; screening, brief intervention, referral, and treatment; secondary outcome; side effect; success; suicidal; time use; treatment-resistant depression

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.

项目摘要 据估计，1500万美国人患有酒精使用障碍（AUD），每年导致95，000人死亡。 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 发现绝大多数患有AUD的人没有接受任何循证治疗。之一 未经治疗的AUD的后果是需要药物治疗以解决急性和慢性影响 大量饮酒，导致与酒精有关的急诊室（艾德）就诊人数增加， 从310万增加到500万，增加了61.6%。这使得艾德成为一个重要而及时的参与环境 AUD患者可以接受成瘾治疗，行为干预措施的成功就证明了这一点，例如 筛查、短暂干预和转诊治疗（SBIRT）。然而，SBIRT并没有对 严重AUD患者，许多ED难以成功实施和维持简短的 干预措施。因此，可以在艾德环境中实施的解决AUD问题的更有效策略包括 急需的。氯胺酮已成为AUD的潜在治疗选择。克他命已经 由于其在治疗精神疾病、迅速减少抑郁和自杀症状方面的潜力， 在患有难治性抑郁症的个体中。亚麻醉剂量的氯胺酮给药， 单次或多次治疗结合心理治疗对患有以下疾病的患者显示出有益的效果： 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 在艾德中用作AUD的有效药物治疗，该方法将与筛选一致， 治疗启动和转诊（STIR），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。 氯胺酮改善寻求戒毒者的AUD相关结果。为了满足这一需求，我们建议 进行一项初步双盲安慰剂对照随机临床试验，主要目的是评估 在艾德向寻求进入住院戒毒单位的AUD患者给予氯胺酮的安全性。 所有参加者将接受医院的标准戒毒治疗，其中还包括密集的 心理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。 和精神病合并症，这些合并症在使用氯胺酮时构成风险。合格的参与者将被随机 被分配在急诊室接受氯胺酮或盐水安慰剂单次输注。生命体征、不良反应， 在整个试验期间，将密切监测酒精戒断和对酒精和氯胺酮的渴望。作为 探索性的目的，我们将评估酒精相关的结果以及行为改变的机制。如果 如果成功，这一系列研究将有助于确定艾德中氯胺酮给药治疗AUD的安全性， 有助于设计具有充分把握度的疗效试验。