Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study
This open-label study (n=13) probed into the efficacy and tolerability of intravenous ketamine in adolescents with treatment-resistant depression (TRD), and investigated clinical response predictors using the Children's Depression Rating Scale-Revised (CDRS-R) and the Clinician-Administered Dissociative States Scale (CADSS). It supported the potential of ketamine in the treatment of adolescent patients with TRD and a dose-response relationship but called for larger sample size and overcoming limitations such as the open-label design and further research.
Authors
- Cullen, K. R.
- Amatya, P.
- Roback, M. G.
Published
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.
Research Summary of 'Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study'
Introduction
Depression often begins in adolescence and can cause substantial disability and suicide risk. Standard pharmacological and psychotherapeutic interventions frequently fail: about 40% of adolescents do not respond to a first treatment and only half of those nonresponders improve with a second trial. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in anaesthesia, has shown rapid antidepressant effects in adults with treatment-resistant depression (TRD), including after single low-dose (0.5 mg/kg) intravenous infusions and in studies of repeated administrations. However, little is known about ketamine's efficacy or tolerability in adolescents, a developmental period with heightened neuroplasticity that might influence both response and duration of benefit. Cullen and colleagues set out to evaluate six serial open-label intravenous ketamine infusions (0.5 mg/kg over 40 minutes) administered across 2 weeks in adolescents with TRD. The study had three aims: to measure the extent and short-term duration of clinical response and remission (primary outcome: percent change on the Children's Depression Rating Scale–Revised, CDRS-R, with response defined as ≥50% reduction and remission as CDRS-R ≤28), to assess tolerability including dissociative and haemodynamic effects, and to explore clinical and demographic predictors of response. The investigators also prespecified a naturalistic follow-up of responders with weekly visits for 6 weeks and a 6-month visit to capture relapse timing and persistence of benefit.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Cullen, K. R., Amatya, P., Roback, M. G., Albott, C. S., Westlund Schreiner, M., Ren, Y., Eberly, L. E., Carstedt, P., Samikoglu, A., Gunlicks-Stoessel, M., Reigstad, K., Horek, N., Tye, S., Lim, K. O., & Klimes-Dougan, B. (2018). Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study. Journal of Child and Adolescent Psychopharmacology, 28(7), 437-444. https://doi.org/10.1089/cap.2018.0030
References (5)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Fond, G., Loundou, A., Macgregor, A. et al. · Psychopharmacology (2014)
Short, B., Fong, J., Galvez, V. et al. · Lancet Psychiatry (2017)
Murrough, J. W., Wan, L., Levitch, C. F. et al. · Journal of Clinical Psychiatry (2015)
Zhu, W., Ding, Z., Zhang, Y. et al. · Neuroscience Bulletin (2016)
Cited By (3)
Papers in Blossom that reference this study
Zhou, Y., Lan, X-F., Wang, C. et al. · Child and Adolescent Psychiatry (2024)
Lan, X-F., Wang, C-Y., Zhang, F. et al. · Child and Adolescent Psychiatry (2023)
Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)
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