Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study

Background: 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. Methods: Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5mg/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). Results: 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. Conclusions: 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.