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

Abstract

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 (0.5 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).

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.

Keywords: adolescent; depression; ketamine; treatment-resistant.

FIG. 1.

Consort diagram summarizing subject flow through the study. We completed initial screening with parents of 36 adolescents. Four participants were screened out due to presence of exclusionary diagnoses, insufficient antidepressant history, or recent medication changes. Parents of 18 adolescents chose not to participate for a variety of reasons, including travel costs, time burden, and safety concerns. Fourteen adolescents completed the consent process and diagnostic interview; one dropped out before receiving infusions. Thirteen adolescents completed all six infusions and posttreatment assessment. Responders were invited back for follow-up visits to measure time to relapse. All five responders completed the week 6 follow-up visit; four of five responders completed the 6-month visit.

FIG. 2.

Mean blood pressure and heart rate, averaged over all six infusions. Maximum elevations of systolic blood pressure were at 30 minutes (mean increase from baseline of 6.8 mmHg) and 45 minutes (mean increase 7.3 mmHg) from the beginning of the infusion. Maximum increase in diastolic blood pressure was 5.1 mmHg, 45 minutes from beginning of infusion. There were no elevations in heart rate or blood pressure during the study that required intervention.

FIG. 3.

CADSS scores across the six infusions. Total CADSS scores are shown before and immediately after the 40-minute infusion, and 1 and 2 hours later. Significant elevations from baseline are denoted by ***p < 0.01 or **p < 0.05. CADSS, Clinician-Administered Dissociative States Scale.