Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study.
Kathryn R. Cullen, Palistha Amatya, Mark G Roback, Christina Sophia Albott, Melinda Westlund Schreiner, Yanan Ren, Lynn E Eberly, Patricia Carstedt, Ali Samikoglu, Meredith Gunlicks-Stoessel, Kristina Reigstad, Nathan Horek, Susannah J. Tye, Kelvin O Lim, Bonnie Klimes-Dougan
Journal of Child and Adolescent Psychopharmacology September 2018 DOI: 10.1089/cap.2018.0030 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Open-label clinical trial Peer reviewed |
|---|---|
| Sample size | 13 |
| Population | Adolescents aged 12-18 years with treatment-resistant depression (failure to respond to two previous antidepressant trials) |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Six infusions over 2 weeks, with 6-week follow-up |
| Measures | Children's Depression Rating Scale-Revised (CDRS-R), Clinician-Administered Dissociative States Scale (CADSS) |
| Topics | Depression Ketamine Esketamine |
| Keywords | Adolescent Treatment-resistant |
| Key findings | Intravenous ketamine produced an average 42.5% decrease in CDRS-R scores, with 5 of 13 adolescents (38%) meeting criteria for clinical response; 3 responders sustained remission at 6-week follow-up while 2 relapsed within 2 weeks. Higher dose predicted treatment response. The authors state these results demonstrate ketamine's potential for treating adolescents with TRD, but caution that the open-label design, small sample, and unknown long-term safety require further research before broader clinical use. |
Abstract
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.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |
Citations in the library
Cited by 35
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial. American Journal of Psychiatry March 3, 2021
- The effectiveness, safety and tolerability of ketamine for depression in adolescents and older adults: A systematic review. Journal of Psychiatric Research March 1, 2021
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial FOCUS: The Journal of Lifelong Learning in Psychiatry April 1, 2022
and 30 more in the library
Cites 7
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression The Journal of Clinical Psychiatry September 2, 2014
- Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant. Neuroscience Bulletin December 2016
and 2 more in the library