Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb 1:15:1325399.
doi: 10.3389/fpsyt.2024.1325399. eCollection 2024.

Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis

Alessandro Rodolico #  1 , Pierfelice Cutrufelli #  1 , Antonio Di Francesco #  1 , Andrea Aguglia  2   3 , Gaetano Catania  1   4 , Carmen Concerto  1 , Alessandro Cuomo  5 , Andrea Fagiolini  5 , Giuseppe Lanza  6   7 , Ludovico Mineo  1 , Antimo Natale  1   8 , Laura Rapisarda  9 , Antonino Petralia  1 , Maria Salvina Signorelli  1 , Eugenio Aguglia  1
Affiliations

Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis

Alessandro Rodolico et al. Front Psychiatry. .

Abstract

Background: Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile.

Methods: Following PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted.

Results: Our analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence.

Limitations: This study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression.

Conclusion: While ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression.

Systematic review registration: [https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).

Keywords: Overview of Reviews; bipolar depression; esketamine; ketamine; suicidal ideation; treatment resistance; unipolar depression.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

References

    1. World Health Organization . Depression and other common mental disorders: global health estimates. Geneva: World Health Organization; (2017).
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington D.C: American Psychiatric Association Publishing; (2022).
    1. GBD 2019 Mental Disorders Collaborators . Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet Psychiatry. (2022) 9:137–50. doi: 10.1016/S2215-0366(21)00395-3 - DOI - PMC - PubMed
    1. Lopizzo N, Chiavetto LB, Cattane N, Plazzotta G, Tarazi FI, Pariante CM, et al. . Gene-environment interaction in major depression: focus on experience-dependent biological systems. Front Psych. (2015) 6:68. doi: 10.3389/fpsyt.2015.00068 - DOI - PMC - PubMed
    1. Dean J, Keshavan M. The neurobiology of depression: an integrated view. Asian J Psychiatr. (2017) 27:101–11. doi: 10.1016/j.ajp.2017.01.025, PMID: - DOI - PubMed

Publication types

LinkOut - more resources