Child Study Center, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Psychiatry and Yale School of Medicine, New Haven, Connecticut, USA.
J Child Adolesc Psychopharmacol. 2024 Mar;34(2):73-79. doi: 10.1089/cap.2023.0047. Epub 2024 Jan 3.
Ketamine has proved effective as a rapid-acting antidepressant agent, but treatment is not effective for everyone (approximately a quarter to a half of patients). Some adult studies have begun to investigate predictors of ketamine's antidepressant response, but no studies have examined this in adolescents with depression. We conducted a secondary data analysis of adolescents who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine for adolescents with treatment-resistant depression. We examined the relationship between 19 exploratory demographic and clinical variables and depression symptom improvement (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) at 1 and 7 days postinfusion. Subjects who had fewer medication trials of both antidepressant medications and augmentation treatments were more likely to experience depression symptom improvement with ketamine. Subjects with shorter duration of their current depressive episode were more likely to experience depression symptom improvement with ketamine. Subjects currently being treated with selective serotonin reuptake inhibitor medications, and not being treated with serotonin-norepinephrine reuptake inhibitor medications, also experienced greater symptom improvement with ketamine. When receiving the midazolam control, less severe depressive symptoms, as measured by the Children's Depression Rating Scale (CDRS) (but not MADRS), and a comorbid attention-deficit/hyperactivity disorder diagnosis were associated with increased response. Findings should be viewed as preliminary and exploratory given the small sample size and multiple secondary analyses. Identifying meaningful predictors of ketamine response is important to inform future therapeutic use of this compound, however, considerably more research is warranted before such clinical guidance is established. The trial was registered in clinicaltrials.gov with the identifier NCT02579928.
氯胺酮已被证明是一种有效的快速抗抑郁药，但并非对所有人都有效（约四分之一到一半的患者）。一些成人研究已经开始研究氯胺酮抗抑郁反应的预测因素，但没有研究在患有抑郁症的青少年中进行过这项研究。我们对参加一项随机、单剂量、咪达唑仑对照交叉试验的青少年进行了二次数据分析，该试验研究了氯胺酮治疗难治性抑郁症青少年的情况。我们研究了 19 个探索性的人口统计学和临床变量与抑郁症状改善（使用蒙哥马利-阿斯伯格抑郁评定量表 [MADRS]）之间的关系，在输注后 1 天和 7 天。接受过较少次数的抗抑郁药物和增效治疗药物试验的患者，使用氯胺酮治疗后更有可能改善抑郁症状。目前抑郁发作持续时间较短的患者，使用氯胺酮治疗后更有可能改善抑郁症状。目前正在接受选择性 5-羟色胺再摄取抑制剂药物治疗，而未接受 5-羟色胺-去甲肾上腺素再摄取抑制剂药物治疗的患者，使用氯胺酮治疗后也能获得更大的症状改善。在接受咪达唑仑对照治疗时，使用氯胺酮治疗时，使用儿童抑郁评定量表（CDRS）（而非 MADRS）测量的抑郁症状较轻，以及合并注意力缺陷/多动障碍诊断，与增加反应相关。鉴于样本量小且进行了多次二次分析，这些发现应被视为初步和探索性的。确定氯胺酮反应的有意义预测因素对于告知该化合物的未来治疗用途非常重要，但是，在建立此类临床指导之前，还需要进行更多的研究。该试验在 clinicaltrials.gov 上注册，标识符为 NCT02579928。
