Cullen Kathryn R, Amatya Palistha, Roback Mark G, Albott Christina Sophia, Westlund Schreiner Melinda, Ren Yanan, Eberly Lynn E, Carstedt Patricia, Samikoglu Ali, Gunlicks-Stoessel Meredith, Reigstad Kristina, Horek Nathan, Tye Susannah, Lim Kelvin O, Klimes-Dougan Bonnie
1 Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Minnesota Medical School , Minneapolis, Minnesota.
2 Departments of Pediatrics and Emergency Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota.
J Child Adolesc Psychopharmacol. 2018 Sep;28(7):437-444. doi: 10.1089/cap.2018.0030. Epub 2018 Jul 13.
Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors.
Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children's Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS).
Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response.
These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.
青少年难治性抑郁症（TRD）的新型干预措施亟待开发。氯胺酮已在成年TRD患者中进行了研究，但针对青少年的相关信息较少。本研究调查了静脉注射氯胺酮治疗青少年TRD的疗效和耐受性，并探索临床反应的预测因素。
选取12 - 18岁的TRD青少年（对之前两次抗抑郁试验均无反应），在2周内给予6次氯胺酮（0.5mg/kg）静脉输注。临床反应定义为儿童抑郁评定量表修订版（CDRS - R）评分降低50%；缓解定义为CDRS - R评分≤28。耐受性评估包括使用临床医生评定的分离状态量表（CADSS）监测生命体征和分离症状。
13名参与者（平均年龄16.9岁，范围14.5 - 18.8岁，8名生物学男性）完成了方案。CDRS - R的平均降低率为42.5%（p = 0.0004）。5名（38%）青少年达到临床反应标准。3名反应者在6周随访时持续缓解；另外2名反应者在2周内复发。氯胺酮输注总体耐受性良好；分离症状和血流动力学症状均为短暂性。较高剂量是治疗反应的显著预测因素。
这些结果表明氯胺酮在治疗青少年TRD方面具有潜在作用。局限性包括开放标签设计和样本量小；需要进一步研究解决这些问题以证实这些结果。此外，有证据表明存在剂量 - 反应关系；需要进一步研究优化剂量。最后，氯胺酮作为抑郁症治疗的长期安全性仍存在疑问；在更广泛临床应用之前需要更多信息。
