氯胺酮对焦虑的影响：成人抑郁症氯胺酮研究的结果

Effect of ketamine on anxiety: findings from the Ketamine for Adult Depression Study.

作者信息

Mills Natalie T, Nikolin Stevan, Glozier Nick, Barton David, Baune Bernhard T, Fitzgerald Paul B, Glue Paul, Sarma Shanthi, Rodgers Anthony, Hadzi-Pavlovic Dusan, Alonzo Angelo, Dong Vanessa, Martin Donel, Mitchell Philip B, Berk Michael, Carter Gregory, Hackett Maree L, Somogyi Andrew A, Mihalopoulos Cathrine, Chatterton Mary Lou, Hood Sean, Loo Colleen K

机构信息

Discipline of Psychiatry, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.

Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, Australia.

出版信息

Br J Psychiatry. 2025 Jan 7:1-7. doi: 10.1192/bjp.2024.250.

DOI:10.1192/bjp.2024.250

PMID:39763417

Abstract

BACKGROUND

Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

AIMS

To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

METHOD

The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5-0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and 'inner tension' item 3 of the Montgomery-Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment ( = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).

RESULTS

In cohort 1 ( = 68) the reduction in HAM-A score was not statistically significant: -1.4 (95% CI [-8.6, 3.2], = 0.37), whereas a significant reduction was seen for cohort 2 ( = 106) of -4.0 (95% CI [-10.6, -1.9], = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 ( = 0.026) but not cohort 1 ( = 0.96).

CONCLUSION

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

摘要

背景

焦虑症与难治性重度抑郁症（TRD）常合并存在。研究表明氯胺酮具有抗焦虑和抗抑郁特性。

目的

研究每周两次皮下注射消旋氯胺酮，持续4周，是否能减轻TRD患者的焦虑症状。

方法

成人抑郁症氯胺酮研究是一项为期4周的多中心随机、双盲、活性（咪达唑仑）对照试验。该研究最初使用固定低剂量氯胺酮（0.5 mg/kg，队列1），之后方案修订为灵活的、根据反应指导的剂量（0.5 - 0.9 mg/kg，队列2）。这项二次分析在基线、4周（治疗结束时）和治疗结束后4周，使用汉密尔顿焦虑量表（HAM - A）（主要测量指标）和蒙哥马利 - 阿斯伯格抑郁评定量表（MADRS）的“内心紧张”第3项来评估焦虑。氯胺酮组和咪达唑仑组之间焦虑变化的分析纳入了所有接受至少一次治疗的参与者（n = 174），采用混合效应重复测量模型来评估主要焦虑测量指标。该试验在www.anzctr.org.au（ACTRN12616001096448）注册。

结果

在队列1（n = 68）中，HAM - A评分的降低无统计学意义：-1.4（95%CI[-8.6, 3.2]，P = 0.37），而队列2（n = 106）有显著降低，为-4.0（95%CI[-10.6, -1.9]，P = 0.0058），表明氯胺酮优于咪达唑仑。这些效应由总MADRS介导，且在治疗结束后4周未维持。队列2中MADRS第3项也显著降低（P = 0.026），但队列1未降低（P = 0.96）。