Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
J Psychiatr Res. 2020 Nov;130:280-285. doi: 10.1016/j.jpsychires.2020.06.012. Epub 2020 Jul 30.
Ketamine has rapid-acting antidepressant properties but also potentially concerning transient dissociative side effects (SEs). Recent studies noted a positive correlation between treatment response to ketamine and general dissociative SEs, as well as "floating", a depersonalization SE (a subtype of the dissociative SEs). This analysis sought to determine whether floating mediates treatment response to ketamine. Data were pooled from three double-blind, crossover, placebo-controlled ketamine clinical trials across which 82 participants with treatment-resistant depression (TRD) (44 with bipolar depression and 38 with major depressive disorder) received placebo and ketamine (0.5 mg/kg) infusions. SEs were actively solicited in a standardized fashion before and after ketamine infusion. The hypothesis that a post-infusion experience of floating would mediate antidepressant response to ketamine was assessed at 230 min post-infusion and at Day 1. Montgomery-Asberg Depression Rating Scale (MADRS) total score was the dependent variable in a linear mixed effects model. Ketamine significantly decreased MADRS scores (p < 0.0001), but no relationship was detected between floating and MADRS score at either 230 min or Day 1 post-infusion. The hypothesized mediation effect of floating was also not detected at either 230 min or Day 1 post-infusion. Taken together, the findings do not support the hypothesis that ketamine's antidepressant effects are mediated by the dissociative depersonalization subtype SE of floating.
氯胺酮具有快速抗抑郁作用，但也可能产生短暂的分离性副作用（SE）。最近的研究表明，氯胺酮治疗反应与一般分离性 SE 以及“漂浮感”（一种分离性 SE 的亚型）之间存在正相关。本分析旨在确定漂浮感是否介导了氯胺酮的治疗反应。数据来自三项双盲、交叉、安慰剂对照的氯胺酮临床试验，共有 82 名治疗抵抗性抑郁症（TRD）患者（44 名双相抑郁症患者和 38 名单相抑郁症患者）接受了安慰剂和氯胺酮（0.5mg/kg）输注。在氯胺酮输注前后以标准化方式主动征集 SE。在输注后 230 分钟和第 1 天评估了漂浮感后体验是否会介导氯胺酮的抗抑郁反应这一假设。Montgomery-Asberg 抑郁评定量表（MADRS）总分是线性混合效应模型中的因变量。氯胺酮显著降低了 MADRS 评分（p<0.0001），但在输注后 230 分钟或第 1 天，漂浮感与 MADRS 评分之间未发现任何关系。在输注后 230 分钟或第 1 天也未检测到漂浮感的假设中介效应。综上所述，这些发现不支持氯胺酮的抗抑郁作用是由漂浮感的分离性去人格化 SE 介导的假设。
