Therapeutic Protocols Using Ketamine and Esketamine for Depressive Disorders: A Systematic Review.
Julia M.k. Freind, Fernando R. Beserra, Bruno S Menezes, Daniel C Mograbi
Journal of Psychoactive Drugs 2024 DOI: 10.1080/02791072.2023.2248989 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Citations | 9 |
| Key findings | Treatment protocols for depression with ketamine or esketamine predominantly follow a medical approach, with limited incorporation of psychosocial elements or psychedelic-assisted therapy modalities. |
Abstract
Depression is one of the most prevalent mental health disorders globally, causing severe emotional suffering, reducing life expectancy and increasing the risk of suicide. Recently, the use of dissociative psychedelic substances such as ketamine and esketamine for depressive disorders has expanded treatment options. We sought to analyze, through a systematic review, the existing protocols for the treatment of depression with ketamine and esketamine. The search adopted PRISMA criteria and was performed using PubMed and Web of Science databases. Procedures in each study were compared, focusing on the sample recruited, therapeutic approaches, including the clinical team and professionals engaged in treatment, medical procedures, description of the setting (including music) and factors such as specific medication (ketamine or esketamine), route of administration and dosage employed. Results indicated the predominance of a medical approach, with a limited number of studies on ketamine assisted psychotherapy (KAP) and other modalities of psychedelic assisted therapy. Additionally, there is limited information on psychosocial elements such as preparation, psychological support during session and integration of experience. Altogether these findings suggest that treatment of depression with ketamine or esketamine diverges in relation to the practices employed with psychedelic substances. This is discussed considering future research directions in the field.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |
Citations in the library
Cited by 6
- Stimulant and hallucinogenic novel psychoactive substances; an update Expert Review of Clinical Pharmacology November 2, 2023
- Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review. Clinical Psychology Review February 2, 2026
- Barriers and Facilitators for Psychedelic Research and Regulation in Brazil: Insights From Diverse Stakeholders Clinical Therapeutics June 1, 2026
- A protocol for a scoping review of psychedelic interventions to alleviate psychological suffering in populations coping with end-of-life issues October 27, 2023
- Novel pharmacotherapies for opioid use disorder and opioid withdrawal Frontiers in Psychiatry September 3, 2026
and 1 more in the library
Cites 56
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 51 more in the library