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Ketamine for major depression in adolescents: a systematic review and meta-analysis of efficacy and safety.

Iury P A Magalhães, Daniel N. Lopes, Isabel Amato, Marcos V.V. Ribeiro, Rodrigo A. Luz, Acioly L T Lacerda, Elson Asevedo, Camila B Martins, Sheila C. Caetano

International Review of Psychiatry 2025 DOI: 10.1080/09540261.2025.2581238 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and meta-analysis Randomized Peer reviewed
Sample size 272
Population Adolescents aged 12-18 years with mood disorders
Intervention Ketamine
Duration 24-hour post-administration assessment
Topics Depression Ketamine Esketamine
Keywords Adolescents Major depression Meta-analysis Suicidality
Key findings In adolescents with mood disorders, ketamine showed a small, non-significant short-term effect on depressive symptoms compared with placebo (SMD = -0.19) and no significant difference in clinical response or remission, but was associated with a significantly higher rate of suicidal ideation remission (RR = 1.49). The authors characterize the evidence as preliminary and call for larger randomized trials with extended follow-up.

Abstract

Major depressive disorder (MDD) significantly impairs adolescents' development, with increasing rates of treatment resistance and suicide risk. Ketamine has emerged as a promising, rapid-acting antidepressant in adults, but its efficacy and safety in adolescents remain unclear. This systematic review and meta-analysis aimed to evaluate short-term outcomes of ketamine administration in youth with mood disorders. Following PRISMA guidelines and PROSPERO registration (CRD42024568658), four studies were included, comprising 272 adolescents aged 12-18 years. Three studies (n = 189) contributed data to the meta-analysis. At 24 hours post-administration, ketamine showed a small, non-significant effect on depressive symptoms compared to placebo (SMD = -0.19; 95% CI: -0.41 to 0.04). Clinical response and remission were not significantly different between groups, but ketamine was associated with a significantly higher rate of suicidal ideation remission (RR = 1.49; 95% CI: 1.06 to 2.08). Adverse events were generally mild, transient, and consistent with known pharmacological effects. While findings support ketamine's potential role in acute presentations, current evidence is preliminary. Larger randomized controlled trials with extended follow-up are needed to clarify the clinical utility, optimal protocols, and long-term safety of this approach in adolescent populations.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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