Jones Gregory H, Vecera Courtney M, Ruiz Ana C, Wu Hanjing E, McInturff Sophia I, Orejarena Maria J, Smith Kacy A, Soares Jair C, Zarate Carlos A, Lane Scott D, Machado-Vieira Rodrigo
Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
J Clin Psychiatry. 2024 Apr 24;85(2):23m14974. doi: 10.4088/JCP.23m14974.
Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic ()-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients. This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN ()-ketamine (or saline comparator) in unmedicated inpatients meeting , Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure. No significant group × time effect was noted for SI ( = 1.1, = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression ( = 3.06, = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD ( =0.927, = .023) that was absent in patients with AUD ( = 0.39, = .44). IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted. ClinicalTrials.gov identifier: NCT03539887.
尽管有酒精使用障碍（AUD）家族史的个体对氯胺酮有更好的抗抑郁反应，但目前患有AUD的患者的治疗结果仍不明确。本研究旨在调查鼻内（IN）消旋（±）-氯胺酮在单相和双相抑郁症中是否具有抗自杀和抗抑郁作用，以及合并AUD是否能为患者带来更好的抗自杀效果。这是一项双盲、随机、安慰剂对照试验（2018年5月至2022年1月），对符合《精神疾病诊断与统计手册》第四版，修订版（DSM-IV-TR）当前重度抑郁发作（双相或单相）标准、有当前自杀意念（SI）和既往自杀未遂史的未用药住院患者单次给予固定剂量（50 mg）的IN（±）-氯胺酮（或生理盐水对照剂）。纳入了合并AUD和未合并AUD的患者。自杀意念量表评分的变化是主要结局指标，蒙哥马利-Åsberg抑郁评定量表评分的变化是次要结局指标。对于SI，未观察到显著的组×时间效应（F = 1.1，P = .36）。在合并AUD的参与者中观察到自杀倾向改善更明显的统计趋势。组×时间交互作用对抑郁改善有显著意义（F = 3.06，P = .03），且在很大程度上不受合并AUD或原发性情绪障碍类型的影响。在氯胺酮组中，未合并AUD的患者抑郁症状改善与SI之间存在显著相关性（r = 0.927，P = .023），而合并AUD的患者中不存在这种相关性（r = 0.39，P = .44）。与安慰剂相比，IN氯胺酮可诱导快速抗抑郁作用，但未显著改变SI评分。该治疗耐受性良好。有必要继续研究将IN氯胺酮作为当前制剂的一种实用替代方案。ClinicalTrials.gov标识符：NCT03539887。
