KETAMINE IN THE TREATMENT OF DEPRESSION - A REVIEW ARTICLE

Olga Szeidl; Jagoda Mikołajczyk; Artur Hawajski; Weronika Mielnicka; Jan Nowak; Stella Mieruszyńska; Julia Sławińska; Maja Kołodziejska; Marcin Lewandowski; Anna Cupiał

doi:10.31435/ijitss.2(50).2026.5066

Authors

Olga Szeidl National Medical Institute of the Ministry of the Interior and Administration, ul. Wołoska 137, 02-507 Warszawa, Poland https://orcid.org/0009-0006-0691-2571
Jagoda Mikołajczyk Warsaw Southern Hospital, Witolda Pileckiego 99, Warsaw, Poland https://orcid.org/0009-0009-1745-5339
Artur Hawajski National Medical Institute of the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland https://orcid.org/0009-0003-7592-2114
Weronika Mielnicka University Clinical Hospital in Bialystok, Maria Skłodowska-Curie 24A, 15-276 Białystok, Poland https://orcid.org/0009-0001-3837-3473
Jan Nowak Dr. Emil Warmiński Clinical Hospital of the Bydgoszcz University of Technology - Independent Public Health Care Facility, Szpitalna 19, 85-826 Bydgoszcz, Kuyavian-Pomeranian, Poland https://orcid.org/0009-0006-8145-8647
Stella Mieruszyńska Franciszek Raszeja Municipal Hospital, Adama Mickiewicza 2, 60-834 Poznań, Poland https://orcid.org/0009-0004-3483-5660
Julia Sławińska Medical University of Lublin, Al. Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0002-3178-7988
Maja Kołodziejska Provincial Polyclinical Hospital in Toruń, ul. Św. Józefa 53/59, 87-100 Toruń, Poland https://orcid.org/0009-0007-1950-3053
Marcin Lewandowski Provincial Polyclinical Hospital in Toruń, ul. Św. Józefa 53/59, 87-100 Toruń, Poland https://orcid.org/0009-0002-4894-2358
Anna Cupiał Greater Poland Cancer Center, ul. Garbary 15, 61-866 Poznań, Poland https://orcid.org/0009-0008-8145-2389

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5066

Keywords:

Ketamine, Eksketamine, Depression, Treatment-Resistant Depression, Neuroplasticity

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.

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