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.

项目摘要摘要 估计有1500万美国人患有酒精疾病（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 发现绝大多数具有AUD的人没有接受任何循证治疗。中的一个 未经处理的AUD的后果是需要医疗解决急性和慢性影响 大量饮酒，这导致了与酒精有关的急诊科（ED）访问的数量 从310万增加到500万。这使ED成为一个重要且及时的参与的设置 具有AUD的人进入成瘾治疗，这是由行为干预成功的成功所证明的 筛查，简短干预和转诊（SBIRT）。但是，Sbirt对 那些具有严重澳元的人，许多EDS很难成功实施和维持简介 干预措施。因此，可以在ED设置中实施以解决AUD的更有效的策略是 至关重要的是。氯胺酮已成为AUD的潜在治疗选择。氯胺酮赢得了 由于其潜力治疗精神疾病而引起的兴趣，抑郁症状和自杀症状迅速​​减轻 在有抗治疗抑郁症的人中。氯胺酮的亚手持剂量 与心理疗法结合的单次或多次会议显示出对患者的有益作用 酒精，阿片类药物和可卡因使用障碍。氯胺酮的主要优势是它已经被接受 在ED中常规使用的药物治疗用于程序性镇静，搅动和急性疼痛。如果氯胺酮可以 用作ED中AUD的有效药物疗法，该方法将与筛查一致， 治疗起始和转诊（搅拌）可能对严重AUD患者更有益 传统的SBIRT方法。然而 氯胺酮可以改善寻求排毒的人改善与听众相关的结果。为了满足这一需求，我们建议 进行试验双盲安慰剂对照的随机临床试验，其主要目的是评估 在ED中给氯胺酮施用氯胺酮的安全性，以寻求入院排毒单元的AUD患者。 所有参与者将获得医院的标准排毒治疗，其中还包括密集型 社会心理支持。参与者的选择将集中于确保排除有潜在医学的人 和精神病合并症，在服用氯胺酮时会构成风险。合格的参与者将随机 被分配在ED中接收单一输注氯胺酮或盐酸安慰剂。生命体征，不利影响， 在整个试验期间，将对饮酒，渴望酒精和氯胺酮的渴望。作为 探索目的，我们将评估与酒精相关的结果以及行为改变的机制。 成功，这项研究将有助于建立氯胺酮管理在ED中的安全性，以及 促进了充分动力效率试验的设计。

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