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Review and Overview
Published Online: 29 January 2025

Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis

Konstantinos N. Fountoulakis, M.D. https://orcid.org/0000-0001-5503-0811 fountoul@auth.gr, Athanasios Saitis, M.D., and Alan F. Schatzberg, M.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
In Advance
https://doi.org/10.1176/appi.ajp.20240515
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Abstract

Objective:

Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review and meta-analysis of the available data on its efficacy against depression and suicidality as well as its side effects.

Methods:

MEDLINE was searched with the keyword “esketamine” on March 24, 2024, using the PRISMA method. Data processing and statistical analysis were performed with R, version 4.3.3, and the meta-analysis was performed with the METAFOR package.

Results:

Of 1,115 articles initially identified, 87 were included for analysis and discussion. At weeks 2–4, randomized controlled trials were mostly negative or failed; however, the meta-analysis returned a weak but significant positive effect for depression (effect size range, 0.15–0.23 at weeks 2–4), similar to augmentation strategies with atypical antipsychotics for treatment-resistant depression. The effect size concerning suicidality was not significant at any time point. The sensitivity analysis produced the same results.

Conclusions:

The study findings suggest that esketamine’s efficacy as an add-on to antidepressants is modest in treatment-resistant depression (similar to augmentation strategies with atypical antipsychotics) and is absent against suicidality itself. These findings need to be considered in light of esketamine’s abuse potential and the fact that long-term effects are still not fully known. Some alarming signs concerning deaths and emerging suicidality during the testing phase are discussed, along with other regulatory issues.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
In Advance

History

Received: 10 June 2024
Revision received: 18 August 2024
Revision received: 20 September 2024
Accepted: 30 September 2024
Published online: 29 January 2025

Keywords

  1. Treatment-Resistant Depression
  2. Depressive Disorders
  3. Suicidality
  4. Ketamine/Esketamine
  5. Meta-Analysis

Authors

Details

Notes

Send correspondence to Dr. Fountoulakis (fountoul@auth.gr).

Competing Interests

Dr. Saitis has received support to participate in congresses from Innovis Pharma and Ricordatti. Dr. Schatzberg has served as a consultant for Alto Neurosciences, ANeurotech, Delpor, Douglas Pharmaceuticals, Galen, HMNC, Johnson & Johnson, Magnus, Mindful Health Solutions, NeuraWell, Owl Insights, Sage, Skyland Trail, Soneira, and Tris; and he has equity in Alto Neurosciences, ANeurotech, Corcept, Madrigal, Magnus, Mindful Health Solutions, NeuraWell, Seattle Genetics, Soneira, and Titan. Dr. Fountoulakis reports no financial relationships with commercial interests.

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