电生理学相关性及预测因素与重复氯胺酮输注治疗难治性抑郁症的抗抑郁反应有关。
Electrophysiological correlates and predictors of the antidepressant response to repeated ketamine infusions in treatment-resistant depression.
机构信息
University of Ottawa Institute of Mental Health Research at the Royal, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada; School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, ON K1N6N5, Canada.
University of Ottawa Institute of Mental Health Research at the Royal, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada; Department of Psychiatry, University of Ottawa, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
出版信息
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Apr 20;115:110507. doi: 10.1016/j.pnpbp.2021.110507. Epub 2021 Dec 28.
BACKGROUND
Sub-anesthetic ketamine doses rapidly reduce depressive symptoms, although additional investigations of the underlying neural mechanisms and the prediction of response outcomes are needed. Electroencephalographic (EEG)-derived measures have shown promise in predicting antidepressant response to a variety of treatments, and are sensitive to ketamine administration. This study examined their utility in characterizing changes in depressive symptoms following single and repeated ketamine infusions.
METHODS
Recordings were obtained from patients with treatment-resistant major depressive disorder (MDD) (N = 24) enrolled in a multi-phase clinical ketamine trial. During the randomized, double-blind, crossover phase (Phase 1), patients received intravenous ketamine (0.5 mg/kg) and midazolam (30 μg/kg), at least 1 week apart. For each medication, three resting, eyes-closed recordings were obtained per session (pre-infusion, immediately post-infusion, 2 h post-infusion), and changes in power (delta, theta1/2/total, alpha1/2/total, beta, gamma), alpha asymmetry, theta cordance, and theta source-localized anterior cingulate cortex activity were quantified. The relationships between ketamine-induced changes with early (Phase 1) and sustained (Phases 2,3: open-label repeated infusions) decreases in depressive symptoms (Montgomery-Åsberg Depression Rating Score, MADRS) and suicidal ideation (MADRS item 10) were examined.
RESULTS
Both medications decreased alpha and theta immediately post-infusion, however, only midazolam increased delta (post-infusion), and only ketamine increased gamma (immediately post- and 2 h post-infusion). Regional- and frequency-specific ketamine-induced EEG changes were related to and predictive of decreases in depressive symptoms (theta, gamma) and suicidal ideation (alpha). Early and sustained treatment responders differed at baseline in surface-level and source-localized theta.
CONCLUSIONS
Ketamine exerts frequency-specific changes on EEG-derived measures, which are related to depressive symptom decreases in treatment-resistant MDD and provide information regarding early and sustained individual response to ketamine.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: Action of Ketamine in Treatment-Resistant Depression, NCT01945047.
背景
亚麻醉剂量的氯胺酮能迅速减轻抑郁症状，但仍需要进一步研究其潜在的神经机制，并预测治疗效果。脑电图（EEG）衍生的测量方法已显示出在预测各种治疗方法的抗抑郁反应方面的潜力，并且对氯胺酮的给药敏感。本研究旨在探讨其在描述单次和重复氯胺酮输注后抑郁症状变化中的作用。
方法
该研究纳入了参加多阶段临床氯胺酮试验的、患有治疗抵抗性重度抑郁症（MDD）的患者（N=24）。在随机、双盲、交叉阶段（第 1 阶段）中，患者至少相隔 1 周接受静脉内氯胺酮（0.5mg/kg）和咪达唑仑（30μg/kg）。对于每种药物，每个疗程都获得三个静息、闭眼记录（输注前、输注后即刻、输注后 2 小时），并量化了功率（delta、theta1/2/total、alpha1/2/total、beta、gamma）、alpha 不对称性、theta 协调性和 theta 源定位前扣带皮层活动的变化。检查了氯胺酮诱导的变化与早期（第 1 阶段）和持续（第 2 阶段、第 3 阶段：开放标签重复输注）抑郁症状（蒙哥马利-阿斯伯格抑郁评定量表，MADRS）和自杀意念（MADRS 第 10 项）降低之间的关系。
结果
两种药物都降低了 alpha 和 theta 波在输注后的即刻，然而，只有咪达唑仑增加了 delta 波（输注后），只有氯胺酮增加了 gamma 波（输注后即刻和 2 小时后）。区域和频率特异性的氯胺酮诱导的 EEG 变化与治疗抵抗性 MDD 的抑郁症状（theta、gamma）和自杀意念（alpha）的降低有关，并具有预测作用。早期和持续的治疗反应者在基线时在表面和源定位 theta 方面存在差异。
结论
氯胺酮对 EEG 衍生测量值产生频率特异性影响，与治疗抵抗性 MDD 的抑郁症状降低有关，并提供了有关氯胺酮早期和持续个体反应的信息。
临床试验注册
ClinicalTrials.gov：氯胺酮在治疗抵抗性抑郁症中的作用，NCT01945047。
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