OBJECTIVE Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes. METHODS Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion. RESULTS Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events. CONCLUSIONS A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.

中文翻译：

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单次氯胺酮输注与动机增强疗法相结合的酒精使用障碍：一项随机的咪达唑仑控制的先导试验。

目的针对酒精滥用障碍的药物治疗和行为疗法的有效性受到限制，具有创新机制的新疗法将是有价值的。在这项前期研究中，作者测试了向患有酒精依赖症的成年人单次麻醉下输注氯胺酮并进行动机增强疗法是否会影响饮酒效果。方法在5周的第二周，将参与者随机分配为52分钟静脉注射氯胺酮（0.71 mg / kg，N = 17）或活性对照咪达唑仑（0.025 mg / kg，N = 23）。门诊动机增强治疗方案。输液后的酒精使用情况通过时间轴跟踪方法进行评估，戒酒通过尿液中的乙基葡糖醛酸测试确定。使用纵向逻辑混合效应模型对氯胺酮输注后21天内每天戒酒的行为进行建模。结果参与者（N = 40）大多为中年（平均年龄= 53岁[SD = 9.8]），主要为白人（70.3％），并且大量就业（71.8％），并且在此之前平均每天喝五杯酒进入研究。与咪达唑仑相比，氯胺酮显着增加了禁欲的可能性，延迟了复发的时间，并减少了大量饮酒的可能性。输液耐受良好，没有因不良事件而退出研究的参与者。结论发现氯胺酮单次输注可改善从事动机增强疗法的酒精依赖者的饮酒措施。这些初步数据提示了针对酒精使用障碍的综合药物疗法-行为治疗的新方向。为了将这些有希望的结果复制到更大的样本中，还需要进一步的研究。