静脉注射氯胺酮,显示出快速的抗抑郁特性,被认为通过迅速增强神经可塑性来逆转抑郁症。作者测试了自动化,基于计算机的方法可以有效地利用增强的神经可塑性来延长快速临床反应的持久性.
共有154名患有难治性单相抑郁症的成年人(年龄18-60岁)以双盲随机分组,平行臂设计接受主动/主动治疗组合(氯胺酮加主动“自动自关联训练”[ASAT];N=53)或两个对照臂中缺乏活性药物成分(盐水加主动ASAT;N=51)或活性行为成分(氯胺酮加假ASAT;N=50)的一个。静脉输注氯胺酮(0.5mg/kg超过40分钟)或惰性安慰剂(盐水)后一天,通过计算机或假ASAT(包括相同的计算机任务,不包括积极或自我参照刺激)提供的自动“评估条件”培训,主动ASAT瞄准自我价值,在连续4天内每天交付两次(八个疗程,每节≤20分钟)。在整个主要(30天)研究期间,预设的主要结局指标是蒙哥马利-奥斯贝格抑郁量表(MADRS)评分。
氯胺酮在输注后24小时迅速且显著降低抑郁评分(各组时间交互作用:标准化β[β]=-1.30,95%CI=-1.89,-0.70;t=-4.29,df=150)。在意图处理线性混合模型中,与生理盐水+ASAT组相比,氯胺酮+ASAT组的抑郁评分在30天研究期间保持显著且稳定的低水平(β=-0.61,95%CI=-0.95,-0.28;t=-3.62,df=148).相比之下,氯胺酮+假治疗后的抑郁评分显著,将线性轨迹从24小时增加到30天,接近盐水+ASAT组观察到的水平(相对于盐水+ASAT组的组间时间相互作用:β=0.015,95%CI=0.003,0.03;t=2.35,df=568).
用氯胺酮启动大脑后,训练积极的自我联想可以提供一种有效的,低成本,便携式,非侵入性,以及利用和延长氯胺酮快速抗抑郁作用的高度传播准备策略。
Intravenous ketamine, which displays rapid antidepressant properties, is posited to reverse depression by rapidly enhancing neuroplasticity. The authors tested whether an automated, computer-based approach could efficiently leverage enhanced neuroplasticity to extend the durability of rapid clinical response.
A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression were randomized in a double-blind, parallel-arm design to receive an active/active treatment combination (ketamine plus active \"automated self-association training\" [ASAT]; N=53) or one of two control arms that lacked either the active drug component (saline plus active ASAT; N=51) or the active behavioral component (ketamine plus sham ASAT; N=50). One day after a single infusion of intravenous ketamine (0.5 mg/kg over 40 minutes) or inert placebo (saline), active ASAT-targeting self-worth through automated \"evaluative conditioning\" training delivered by computer-or sham ASAT (consisting of identical computer tasks that included no positive or self-referential stimuli) was given, delivered twice daily over 4 consecutive days (eight sessions, ≤20 minutes per session). The prespecified primary outcome measure throughout the main (30-day)
study period was score on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Ketamine rapidly and significantly reduced depression scores at 24 hours postinfusion (group-by-time interaction: standardized beta [β]=-1.30, 95% CI=-1.89, -0.70; t=-4.29, df=150). In intent-to-treat linear mixed models, depression scores in the ketamine+ASAT group remained significantly and stably low over the 30-day
study period relative to those of the saline+ASAT group (β=-0.61, 95% CI=-0.95, -0.28; t=-3.62, df=148). By contrast, depression scores following ketamine+sham treatment followed a significant, increasing linear trajectory from 24 hours to 30 days, approaching the levels observed in the saline+ASAT group (group-by-time interaction relative to the saline+ASAT group: β=0.015, 95% CI=0.003, 0.03; t=2.35, df=568).
After priming the brain with ketamine, training positive self-associations could provide an efficient, low-cost, portable, noninvasive, and highly dissemination-ready strategy for leveraging and extending ketamine\'s rapid antidepressant effects.