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：一项试点双盲、安慰剂对照随机临床试验

• 批准号: 10703512
• 负责人: Peter R Chai
• 金额: $ 21.26万
• 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/10703512
• 关键词: Abstinence; Accident and Emergency department; Acute; Acute Pain; Address; Admission activity; Adverse effects; Agitation; 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; 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; United States National Institutes of Health; Urine; Withdrawal; addiction; adverse drug reaction; alcohol abuse therapy; alcohol craving; alcohol use disorder; alcohol-related death; antagonist; behavior change; brief intervention; craving; depressive symptoms; design; drinking; efficacy evaluation; efficacy trial; eligible participant; epidemiology study; experience; follow up assessment; hypertensive; implementation strategy; improved; innovation; interest; opioid use disorder; patient engagement; phosphatidylethanol; primary outcome; psychiatric comorbidity; randomized placebo controlled trial; randomized placebo-controlled clinical trial; safety assessment; 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.

项目概要摘要 据估计，有 1500 万美国人患有酒精使用障碍 (AUD)，每年导致 95,000 人因此死亡 然而，流行病学研究一致表明，酒精相关原因和 2500 亿美元的经济负担。 发现绝大多数 AUD 患者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来解决急性和慢性影响 酗酒，导致因酒精相关的急诊科 (ED) 就诊的次数 增加了 61.6%，从 310 万增加到 500 万，这使得 ED 成为重要而及时的参与场所。 患有 AUD 的个体进入成瘾治疗，行为干预的成功证明，例如 筛查、简短干预和转诊治疗 (SBIRT) 然而，SBIRT 的影响力并不大。 那些患有严重 AUD 的人，许多 ED 很难成功地实施和维持简短的 因此，可以在急诊室实施更有效的策略来解决 AUD 问题。 氯胺酮已成为 AUD 的潜在治疗选择。 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而引起人们的兴趣 在患有难治性抑郁症的个体中，服用亚麻醉剂量的氯胺酮。 与心理治疗相结合的单次或多次治疗已显示出对患有以下疾病的患者有益的效果 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被接受。 急诊科常规使用的药物疗法用于镇静、躁动和急性疼痛（如果氯胺酮可以）。 用作 ED 中 AUD 的有效药物疗法，该方法将与筛选一致， 治疗启动和转诊 (STIR) 对于严重 AUD 患者来说可能比常规治疗更有益 然而，对于 ED 发起的安全性的理解仍然存在很大差距。 氯胺酮可改善寻求戒毒者的 AUD 相关结果 为了满足这一需求，我们建议： 进行一项试点双盲安慰剂对照随机临床试验，主要目的是评估 在急诊室向寻求住院戒毒病房的 AUD 患者施用氯胺酮的安全性。 所有参与者都将接受医院的标准戒毒治疗，其中还包括强化治疗 参与者的选择将侧重于确保排除那些有潜在医疗潜力的人。 服用氯胺酮时会产生风险的精神并发症将被随机分配。 被分配在急诊室接受单次氯胺酮输注或生理盐水安慰剂。 在整个试验过程中，将密切监测酒精戒断以及对酒精和氯胺酮的渴望。 为了探索性目标，我们将评估与酒精相关的结果以及行为改变的机制。 如果成功，这一系列研究将有助于确定急诊科 AUD 氯胺酮给药的安全性，以及 促进设计充分有力的功效试验。

项目成果

The possible clinical utility of the alcohol biomarker phosphatidylethanol for managing suspected alcohol withdrawal in hospitalized patients: A case report.

酒精生物标志物磷脂酰乙醇在治疗住院患者疑似酒精戒断方面的可能临床效用：病例报告。

• DOI: 10.1111/ajad.13516
• 发表时间: 2024
• 期刊: The American journal on addictions
• 作者: Edinoff,AmberN;Hathaway,DavidB;MartinezGarza,David;Rosen,JordanH;Suzuki,Joji
• 通讯作者: Suzuki,Joji