Intravenous Ketamine or Esketamine in Adolescents With Major Depressive Disorder: A Systematic Review
5 affiliations
- 1Department of Psychiatry, The Brain Hospital of Guangxi Zhuang Autonomous Region, 545005 Liuzhou, Guangxi, China
- 2School of Clinical Medicine, School of Graduate Studies, Youjiang Medical University for Nationalities, 533000 Baise, Guangxi, China
- 3Department of Psychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, 510370 Guangzhou, Guangdong, China
- 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, 510260 Guangzhou, Guangdong, China
- 5Department of Medical Administration, Liuzhou Health Commission, 545001 Liuzhou, Guangxi, China
Abstract
Background:: The therapeutic efficacy and safety of intravenous ketamine or esketamine in adolescents with major depressive disorder (MDD) remain insufficiently defined. This systematic review of randomized controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of intravenous ketamine or esketamine in this population.
Methods:: A comprehensive search of four international databases (PubMed, EMBASE, PsycINFO, and the Cochrane Library) was conducted to identify RCTs comparing intravenous ketamine or esketamine with intravenous midazolam in adolescents with MDD.
Results:: Three RCTs involving a total of 134 adolescents with MDD were included. Two trials assessed the antidepressant effects of intravenous ketamine compared with intravenous midazolam, with inconsistent findings. No significant advantage of intravenous ketamine over intravenous midazolam was observed in reducing anxiety symptoms (1 RCT). One trial compared intravenous esketamine with intravenous midazolam and evaluated antidepressant, anti-suicidal, and neurocognitive outcomes, demonstrating the superiority of intravenous esketamine. Both intravenous ketamine and intravenous esketamine were associated with significantly higher rates of dissociative symptoms (1 RCT each), and intravenous esketamine was also linked to a higher incidence of psychopathological symptoms (1 RCT). Systematic reporting of adverse events was provided in only one of the three included RCTs.
Conclusions:: Given the limited number of studies, small sample sizes, and methodological heterogeneity of the available RCTs, the current evidence base remains preliminary and insufficient to support definitive conclusions regarding the efficacy and safety of intravenous ketamine/esketamine in adolescents with MDD. These findings highlight the need for further adequately powered RCTs to establish robust and clinically meaningful evidence.
Related
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders
- Intravenous Ketamine for Depressed and Suicidal Adolescents in the Emergency Department: A Randomized Double-Blind Trial.
- Association of Milk and Dairy Intake with Anxiety and Depressive Symptoms in Children and Adolescents: A Systematic Review and Meta-Analysis
- Effects of insomnia-focused psychological and behavioral interventions on depressive symptoms in children and adolescents: a systematic review and meta-analysis
- Effect of Adding Esketamine to Patient-Controlled Intravenous Analgesia on Rebound Pain After Interscalene Brachial Plexus Block: A Randomized Controlled Trial
BibTeX
@article{qin2026intravenous,
title = {{Intravenous Ketamine or Esketamine in Adolescents With Major Depressive Disorder: A Systematic Review}},
author = {Zhen-Juan Qin and Xiao-Ming Li and Jia-Bao Li and Zhi Li and Xin Wei and Hui-Lin Hu and Yu-Jiao Chen and Su-Rong Xu and Zhi-Yuan Xie and Xin-Hu Yang and Wen-Juan Dai and Yu-Hua Wei},
journal = {Alpha Psychiatry},
year = {2026},
month = aug,
doi = {10.31083/ap48866},
url = {https://doi.org/10.31083/ap48866},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intravenous Ketamine or Esketamine in Adolescents With Major Depressive Disorder: A Systematic Review
AU - Zhen-Juan Qin
AU - Xiao-Ming Li
AU - Jia-Bao Li
AU - Zhi Li
AU - Xin Wei
AU - Hui-Lin Hu
AU - Yu-Jiao Chen
AU - Su-Rong Xu
AU - Zhi-Yuan Xie
AU - Xin-Hu Yang
AU - Wen-Juan Dai
AU - Yu-Hua Wei
PY - 2026
DA - 2026/08/27
JO - Alpha Psychiatry
DO - 10.31083/ap48866
UR - https://doi.org/10.31083/ap48866
AB - Background:: The therapeutic efficacy and safety of intravenous ketamine or esketamine in adolescents with major depressive disorder (MDD) remain insufficiently defined. This systematic review of randomized controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of intravenous ketamine or esketamine in this population. Methods:: A comprehensive search of four international databases (PubMed, EMBASE, PsycINFO, and the Cochrane Library) was conducted to identify RCTs comparing intravenous ketamine or esketamine with intravenous midazolam in adolescents with MDD. Results:: Three RCTs involving a total of 134 adolescents with MDD were included. Two trials assessed the antidepressant effects of intravenous ketamine compared with intravenous midazolam, with inconsistent findings. No significant advantage of intravenous ketamine over intravenous midazolam was observed in reducing anxiety symptoms (1 RCT). One trial compared intravenous esketamine with intravenous midazolam and evaluated antidepressant, anti-suicidal, and neurocognitive outcomes, demonstrating the superiority of intravenous esketamine. Both intravenous ketamine and intravenous esketamine were associated with significantly higher rates of dissociative symptoms (1 RCT each), and intravenous esketamine was also linked to a higher incidence of psychopathological symptoms (1 RCT). Systematic reporting of adverse events was provided in only one of the three included RCTs. Conclusions:: Given the limited number of studies, small sample sizes, and methodological heterogeneity of the available RCTs, the current evidence base remains preliminary and insufficient to support definitive conclusions regarding the efficacy and safety of intravenous ketamine/esketamine in adolescents with MDD. These findings highlight the need for further adequately powered RCTs to establish robust and clinically meaningful evidence.
SN - 2757-8038
ER -