氯胺酮加纳曲酮治疗重度抑郁症合并酒精使用障碍的抗抑郁疗效:一项随机对照试验

IF 3.7 2区 医学 Q1 CLINICAL NEUROLOGY
Gihyun Yoon, Brian Pittman, Elizabeth Ralevski, Ismene L Petrakis, John H Krystal
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引用次数: 0

摘要

重要性:重度抑郁症(MDD)和酒精使用障碍(AUD)的共病通常治疗不充分。本研究评估了阿片受体阻滞剂纳曲酮与NMDA谷氨酸受体拮抗剂氯胺酮联合治疗重度抑郁症合并AUD的影响。在这样做的过程中,它也试图阐明阿片受体刺激对氯胺酮在这一人群中的抗抑郁作用的贡献。目的:比较氯胺酮加纳曲酮与氯胺酮加生理盐水、咪达唑仑加生理盐水对MDD和AUD合并症门诊患者减轻抑郁和减少饮酒的疗效。设计、环境和参与者:进行了一项三组、随机、双盲、平行组研究。参与者为65名患有重度抑郁症和AUD的成年人,Montgomery-Åsberg抑郁评定量表(MADRS)总分为20分或更高,在随机分组前一个月内至少重度饮酒4次。干预措施:随机(1:1:1)接受1)静脉注射(静脉注射)氯胺酮(0.5 mg/kg),每周1次,共4次,加肌注(IM)纳曲酮(380 mg), 2)静脉注射氯胺酮加IM生理盐水,或3)静脉注射咪达唑仑(0.045 mg/kg)加IM生理盐水。主要结果和措施:共同主要:MADRS;完全戒酒。其次:嗜酒、焦虑、生活质量、安全。结果:65名参与者中,58人接受了至少一次氯胺酮/咪达唑仑输注:20人接受氯胺酮纳曲酮输注,19人接受氯胺酮生理盐水输注,19人接受咪达唑仑生理盐水输注。各组均有显著改善(抑郁缓解80%)。治疗期间的MADRS变化(主要结局)没有观察到组间差异,尽管与咪达唑仑相比,氯胺酮组的抗抑郁作用持续时间更长。在酒精相关的结果上没有显著的组间差异。氯胺酮组比咪达唑仑组在焦虑和生活质量(次要结局)方面有更大的改善,氯胺酮-纳曲酮组比氯胺酮-生理盐水组在焦虑方面有更大的改善。无研究相关的严重不良事件。结论和相关性:本研究发现三组患者的抗抑郁和抗酒精效果相似。与咪达唑仑相比,氯胺酮组表现出更持久的抗抑郁效果,在焦虑和生活质量方面也有更大的改善。两个氯胺酮组的比较结果表明,阿片受体拮抗剂并没有改变氯胺酮的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: a randomized controlled trial.

Importance: The comorbidity of major depressive disorder (MDD) and alcohol use disorder (AUD) is often treated inadequately. This study evaluated the impact of adding the opioid receptor blocker, naltrexone, to the NMDA glutamate receptor antagonist, ketamine, for the treatment of MDD comorbid with AUD. In so doing, it also attempted to shed light on the contribution of opioid receptor stimulation to the antidepressant effects of ketamine in this population.

Objective: To compare the efficacy of ketamine plus naltrexone to ketamine plus saline and midazolam plus saline for reducing depression and decreasing alcohol consumption in outpatients with comorbid MDD and AUD.

Design, setting, and participants: A 3-arm, randomized, double-blind, parallel-group study was conducted. Participants were 65 adults with current MDD and AUD, with Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 20 or higher and heavy drinking at least 4 times in the month prior to randomization.

Interventions: Randomized (1:1:1) to receive (1) intravenous (IV) ketamine (0.5 mg/kg) once a week for 4 weeks (a total of 4 infusions) plus intramuscular (IM) naltrexone (380 mg), (2) IV ketamine plus IM saline, or (3) IV midazolam (0.045 mg/kg) plus IM saline.

Main outcomes and measures: Co-primary: MADRS; complete alcohol abstinence. Secondary: alcohol craving, anxiety, quality of life, safety.

Results: Of 65 participants, 58 received at least 1 ketamine/midazolam infusion: 20 in ketamine-naltrexone, 19 in ketamine-saline, 19 in midazolam-saline. All groups improved significantly (>80% depression remission). No group differences were observed in MADRS changes during treatment (primary outcome), although antidepressant effects persisted longer in ketamine groups compared to midazolam. There were no significant group differences in alcohol-related outcomes. Ketamine groups showed greater improvement in anxiety and quality of life (secondary outcomes) than midazolam, with the ketamine-naltrexone group showing greater improvement in anxiety than ketamine-saline. No study-related serious adverse events.

Conclusions and relevance: This study found similar antidepressant and anti-alcohol effects across 3 groups. Compared to midazolam, the ketamine groups showed longer-lasting antidepressant effects and greater improvements in anxiety and quality of life. Comparable outcomes between the 2 ketamine groups suggest opioid receptor antagonism did not alter ketamine's therapeutic effects.

Clinical trial registration: The study was registered at ClinicalTrials.gov (Identifier: NCT02461927).

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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