KETAMINE IN THE TREATMENT OF DEPRESSION - A REVIEW ARTICLE
Olga Szeidl, Joanna Mikołajczyk, Artur Hawajski, Weronika Mielnicka, Jan Nowak, Stella Mieruszyńska, Julia Sławińska, Maja Kołodziejska, Marcin Lewandowski, Anna Cupiał
International Journal of Innovative Technologies in Social Science June 15, 2026 DOI: 10.31435/ijitss.2(50).2026.5066 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review article Randomized Peer reviewed |
|---|---|
| Interventions | Ketamine Esketamine Ketamine-assisted psychotherapy |
| Dose | subanesthetic |
| Topics | Depression Ketamine Esketamine |
| Keywords | Depression economics Antidepressant Psychological intervention Review article Pharmacotherapy Modalities Psychotherapist Therapeutic window Adverse effect Systematic review Intensive care medicine Vortioxetine |
| Key findings | Subanesthetic intravenous or intranasal ketamine produces rapid antidepressant effects within hours and reduces suicidal ideation in treatment-resistant depression. |
Abstract
Background: Depression is a multifactorial disorder involving neurotransmitter dysregulation, HPA axis hyperactivity, neuroinflammation, and impaired neuroplasticity. While combination psychotherapy and pharmacotherapy remains first-line, ~30% of patients develop TRD. In the last few years ketamine has emerged as a rapid-acting therapeutic option for treatment-resistant cases.
Aim: To review the etiology, treatment options, and emerging interventions for major depressive disorder (MDD), with a particular focus on treatment-resistant depression (TRD) and the therapeutic potential of ketamine and ketamine-assisted psychotherapy (KAP).
Methods: A comprehensive literature review was conducted, analyzing 29 studies from the PubMed database (English-language, up to October 2025) that assess the etiology, treatment options of depression with emphasis on the therapeutic role of ketamine, especially in treatment-resistant depression (TRD).
Results: Subanesthetic intravenous or intranasal ketamine produces rapid antidepressant effects within hours, reduces suicidal ideation, and enhances synaptic connectivity through AMPA receptor, BDNF, and mTOR signaling. KAP leverages this neuroplastic window to consolidate cognitive and emotional restructuring. Intranasal esketamine has received FDA and EMA approval as adjunctive therapy for TRD. Ketamine is generally well-tolerated, though patient selection, monitoring, and adherence to safety protocols are essential.
Conclusions: Ketamine and KAP represent transformative interventions for TRD, offering rapid symptom relief and potential enhancement of psychotherapeutic outcomes. Further large-scale, randomized studies are required to optimize treatment protocols, understand long-term efficacy, and determine the additive benefits of psychotherapy.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |