Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial
Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial
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DOI：
10.1176/appi.ajp.2020.20010018
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发表时间：
2021-04-01
影响因子：
17.7
通讯作者：
Bloch, Michael H.
中科院分区：
文献类型：
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作者：
Dwyer, Jennifer B.;Landeros-Weisenberger, Angeli;Bloch, Michael H.
目的：青少年抑郁症很普遍，并且与显着的发病率和死亡率相关。尽管静脉注射氯胺酮已显示出对成人难治性抑郁症的疗效，但其对儿童人群的疗效尚不清楚。作者对青少年中氯胺酮的安全性和有效性进行了一项主动安慰剂对照研究。 方法：在这项概念验证随机、双盲、单剂量交叉临床试验中，17 名诊断为重度抑郁症的青少年（13-17 岁）接受单次静脉输注氯胺酮（0.5 mg/kg，持续 40 分钟）或咪达唑仑（0.045 mg/kg，持续 40 分钟）。分钟），两周后使用替代化合物。所有参与者之前都曾尝试过至少一种抗抑郁药物，并且符合儿童抑郁评定量表修订版得分 >40 的严重标准。主要结局指标是治疗后 24 小时蒙哥马利-阿斯伯格抑郁评定量表 (MADRS) 评分。结果：与咪达唑仑相比，单次氯胺酮输注可显着减轻输注后 24 小时的抑郁症状（MADRS 评分：咪达唑仑，平均值 = 24.13，SD = 12.08，95% CI = 18.21，30.04；氯胺酮，平均值=15.44，SD=10.07，95% CI=10.51，20.37；平均差=28.69，SD=15.08，95% CI=216.72，20.65，df=15；效应量=0.78）。在二次分析中，与氯胺酮相关的治疗效果似乎在治疗后 14 天保持不变，这是根据 MADRS 测量的最新评估时间点（但不是根据儿童抑郁评定量表修订版测量的）。与咪达唑仑相比，输注后前 3 天内对氯胺酮产生反应的参与者比例明显更高（分别为 76% 和 35%）。氯胺酮与短暂的、自限性的解离症状相关，影响参与者致盲，但没有发生严重的不良事件。结论：在这项针对患有抑郁症的青少年进行的首个静脉注射氯胺酮随机安慰剂对照临床试验中，研究结果表明，与活性安慰剂相比，氯胺酮具有良好的急性耐受性，并且在减少抑郁症状方面具有显着的短期（2 周）疗效。
Objective: 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.Methods: 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-Asberg Depression Rating Scale (MADRS) 24 hours after treatment.Results: 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=28.69, SD=15.08, 95% CI=216.72, 20.65, 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.Conclusions: 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.