Yale Child Study Center (Dwyer, Landeros-Weisenberger, Johnson, Londono Tobon, Flores, Nasir, Bloch), Department of Radiology and Biomedical Imaging (Dwyer), and Department of Psychiatry (Londono Tobon, Flores, Sanacora, Bloch), Yale School of Medicine, New Haven, Conn.; Department of Pediatrics, Stanford University, Stanford, Calif. (Couloures).
Am J Psychiatry. 2021 Apr 1;178(4):352-362. doi: 10.1176/appi.ajp.2020.20010018. Epub 2021 Mar 3.
Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents.
In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes), and the alternate compound 2 weeks later. All participants had previously tried at least one antidepressant medication and met the severity criterion of a score >40 on the Children's Depression Rating Scale-Revised. The primary outcome measure was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment.
A single ketamine infusion significantly reduced depressive symptoms 24 hours after infusion compared with midazolam (MADRS score: midazolam, mean=24.13, SD=12.08, 95% CI=18.21, 30.04; ketamine, mean=15.44, SD=10.07, 95% CI=10.51, 20.37; mean difference=-8.69, SD=15.08, 95% CI=-16.72, -0.65, df=15; effect size=0.78). In secondary analyses, the treatment gains associated with ketamine appeared to remain 14 days after treatment, the latest time point assessed, as measured by the MADRS (but not as measured by the Children's Depression Rating Scale-Revised). A significantly greater proportion of participants experienced a response to ketamine during the first 3 days following infusion as compared with midazolam (76% and 35%, respectively). Ketamine was associated with transient, self-limited dissociative symptoms that affected participant blinding, but there were no serious adverse events.
In this first randomized placebo-controlled clinical trial of intravenous ketamine in adolescents with depression, the findings suggest that it is well tolerated acutely and has significant short-term (2-week) efficacy in reducing depressive symptoms compared with an active placebo.
青少年抑郁症较为普遍，与较高的发病率和死亡率密切相关。虽然静脉注射氯胺酮在成人治疗性抵抗性抑郁症中显示出疗效，但在儿科人群中的疗效尚不清楚。作者开展了一项氯胺酮治疗青少年抑郁症的安全性和疗效的安慰剂对照研究。
这是一项概念验证性、随机、双盲、单次剂量交叉临床试验，17 名年龄在 13-17 岁之间、被诊断为重度抑郁症的青少年患者接受单次静脉输注氯胺酮（40 分钟内输注 0.5mg/kg）或咪达唑仑（40 分钟内输注 0.045mg/kg），两周后接受另一种化合物。所有参与者之前至少尝试过一种抗抑郁药物，且符合儿童抑郁评定量表修订版（Children's Depression Rating Scale-Revised）评分>40 的严重程度标准。主要结局指标为治疗后 24 小时的蒙哥马利-阿斯伯格抑郁评定量表（Montgomery-Åsberg Depression Rating Scale，MADRS）评分。
与咪达唑仑相比，单次氯胺酮输注可显著降低 24 小时后的抑郁症状（MADRS 评分：咪达唑仑，平均值=24.13，标准差=12.08，95%置信区间=18.21，30.04；氯胺酮，平均值=15.44，标准差=10.07，95%置信区间=10.51，20.37；平均值差=-8.69，标准差=15.08，95%置信区间=-16.72，-0.65，df=15；效应大小=0.78）。在二次分析中，正如 MADRS 所测量的（而非儿童抑郁评定量表修订版），与治疗相关的氯胺酮治疗获益似乎在治疗后 14 天（评估的最晚时间点）仍持续存在。与咪达唑仑相比，在输注后前 3 天内，有更多的参与者对氯胺酮有反应（分别为 76%和 35%）。氯胺酮引起短暂、自我限制的分离症状，影响参与者的盲法，但无严重不良事件。
在这项青少年抑郁症患者中首次氯胺酮静脉注射的随机安慰剂对照临床试验中，结果表明，它在急性治疗中耐受性良好，与活性安慰剂相比，在短期（2 周）内降低抑郁症状方面具有显著疗效。
