Sympathetic activation but not dissociation linked to ketamine's sustained antidepressant effect.

IF 5 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Therapeutic Advances in Psychopharmacology Pub Date : 2026-02-20 eCollection Date: 2026-01-01 DOI:10.1177/20451253261419636
Veronika Andrashko, Tomas Novak, Miloslav Kopecek, Anna Sulakova, Vit Knop, Jiri Horacek
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引用次数: 0

Abstract

Background: Ketamine is a rapid-acting antidepressant with robust evidence, but unclear predictors of therapeutic response.

Objectives: Based on previous knowledge, hemodynamic parameters and acute altered state of consciousness have been hypothesized as potential correlates of subsequent antidepressant outcome.

Design: A post hoc analysis was performed using the data from an open-label study, in which 39 patients with depression received a single intravenous infusion of ketamine (0.54 mg/kg). Antidepressant response was defined as ⩾50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 7.

Methods: Systolic and diastolic blood pressure (SBP and DBP), heart rate, Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS) were assessed during the infusion, alongside plasma levels of ketamine and norketamine. Data were analyzed using mixed-effects models and correlation and regression techniques.

Results: Responders exhibited significantly higher SBP and DBP during ketamine infusion compared with nonresponders. The degree of dissociation or psychotomimetic symptoms during the infusion did not differ significantly between responders and nonresponders. Antipsychotic (AP) augmentation was associated with worse antidepressant outcome as well as with lower infusion-related blood pressure values. CADSS and BPRS did not differ between AP users and nonusers. None of the parameters correlated with plasma levels of ketamine or norketamine.

Conclusion: Higher blood pressure during ketamine administration was associated with better antidepressant outcome, supporting the hypothesis concerning sympathetic activation in treatment responders. Psychological parameters (as measured by CADSS and BPRS) were not linked to subsequent outcomes and did not resolve inconsistencies in previous studies. Concomitant antipsychotic medication attenuated ketamine's antidepressant effects.

Trial registration: EudraCT 2018-001539-39.

交感神经激活而非解离与氯胺酮持续的抗抑郁作用有关。
背景:氯胺酮是一种速效抗抑郁药,有强有力的证据,但尚不清楚治疗反应的预测因素。目的:基于先前的知识,血液动力学参数和急性意识状态改变被假设为随后抗抑郁结果的潜在相关因素。设计:使用一项开放标签研究的数据进行事后分析,其中39例抑郁症患者接受单次静脉输注氯胺酮(0.54 mg/kg)。在第7天,在Montgomery-Åsberg抑郁评定量表(MADRS)中,抗抑郁反应被定义为小于或等于50%。方法:在输注过程中评估收缩压和舒张压(SBP和DBP)、心率、临床管理的解离状态量表(CADSS)和简短精神病学评定量表(BPRS),以及血浆氯胺酮和诺氯胺酮的水平。数据分析采用混合效应模型和相关及回归技术。结果:与无反应者相比,反应者在氯胺酮输注期间表现出明显更高的收缩压和舒张压。在输注期间,反应者和无反应者的分离程度或拟精神症状没有显著差异。抗精神病药(AP)增强与更差的抗抑郁结果以及更低的输注相关血压值相关。CADSS和BPRS在AP用户和非用户之间没有差异。这些参数都与氯胺酮或去甲氯胺酮的血浆水平无关。结论:氯胺酮给药期间血压升高与抗抑郁效果较好相关,支持了治疗应答者交感神经激活的假设。心理参数(由CADSS和BPRS测量)与随后的结果无关,并且不能解决先前研究中的不一致。同时服用抗精神病药物会减弱氯胺酮的抗抑郁作用。试验注册:edract 2018-001539-39。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
2.40%
发文量
35
审稿时长
10 weeks
期刊介绍: Therapeutic Advances in Psychopharmacology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of psychopharmacology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in psychopharmacology, providing a forum in print and online for publishing the highest quality articles in this area.
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