Michael E. DeBakey VA Medical Center, 2002 Holcomb Boulevard, Houston, TX, 77030, USA; Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, 1977 Butler Boulevard, Houston, TX, 77030, USA. Electronic address: brittany.o'
Michael E. DeBakey VA Medical Center, 2002 Holcomb Boulevard, Houston, TX, 77030, USA; Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, 1977 Butler Boulevard, Houston, TX, 77030, USA.
J Affect Disord. 2021 May 1;286:320-329. doi: 10.1016/j.jad.2021.03.006. Epub 2021 Mar 9.
The N-methyl-D-aspartate receptor antagonist ketamine is potentially effective in treatment resistant depression. However, its antidepressant efficacy is highly variable, and there is little information about predictors of response.
We employed growth mixture modeling (GMM) analysis to examine specific response trajectories to intravenous (IV) ketamine (three infusions; mean dose 0.63 mg/kg, SD 0.28, range 0.30 - 2.98 mg/kg over 40 min) in 328 depressed adult outpatients referred to a community clinic. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) assessed depression severity at baseline and before each infusion, up to three infusions for four total observations.
GMM revealed three QIDS-SR response trajectories. There were two groups of severely depressed patients, with contrasting responses to ketamine. One group (n=135, baseline QIDS-SR=18.8) had a robust antidepressant response (final QIDS-SR=7.3); the other group (n=97, QIDS-SR=19.8) was less responsive (final QIDS-SR=15.6). A third group (n=96) was less severely depressed at baseline (QIDS-SR=11.7), with intermediate antidepressant response (final QIDS-SR=6.6). Comparisons of demographic and clinical characteristics between groups with severe baseline depression revealed higher childhood physical abuse in the group with robust ketamine response (p=0.01).
This was a retrospective analysis on a naturalistic sample. Patients were unblinded and more heterogenous than those included in most controlled clinical trial samples. Information pertaining to traumatic events occurring after childhood and pre-existing or concurrent medical conditions that may have affected outcomes was not available.
Overall, ketamine's effect in patients with severe baseline depression and history of childhood maltreatment may be consistent with ketamine-induced blockade of behavioral sensitization.
N-甲基-D-天冬氨酸受体拮抗剂氯胺酮在治疗抵抗性抑郁症方面可能具有疗效。然而，其抗抑郁疗效高度可变，并且关于反应预测因素的信息很少。
我们采用增长混合物建模（GMM）分析，来检查 328 名接受社区诊所转介的成年门诊抑郁症患者对静脉注射（IV）氯胺酮（三次输注；平均剂量 0.63mg/kg，标准差 0.28，范围 0.30-2.98mg/kg，在 40 分钟内输注）的具体反应轨迹。在基线和每次输注前（共输注四次，总共进行了四次观察），使用快速抑郁症状自评量表（QIDS-SR）评估抑郁严重程度。
GMM 揭示了三种 QIDS-SR 反应轨迹。有两组严重抑郁的患者，对氯胺酮的反应截然不同。一组（n=135，基线 QIDS-SR=18.8）有很强的抗抑郁反应（最终 QIDS-SR=7.3）；另一组（n=97，QIDS-SR=19.8）反应性较差（最终 QIDS-SR=15.6）。第三组（n=96）基线时抑郁程度较低（QIDS-SR=11.7），抗抑郁反应处于中间水平（最终 QIDS-SR=6.6）。对基线严重抑郁组之间的人口统计学和临床特征进行比较发现，在对氯胺酮反应较强的组中，童年时期身体虐待的发生率较高（p=0.01）。
这是对自然样本的回顾性分析。与大多数对照临床试验样本相比，患者未设盲且更具异质性。没有关于儿童期后发生的创伤事件以及可能影响结局的预先存在或并发的医疗条件的信息。
总体而言，氯胺酮在基线严重抑郁和童年期受虐史患者中的作用可能与氯胺酮诱导的行为敏感化阻断一致。
