Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis
Alessandro Rodolico, Pierfelice Cutrufelli, Antonio Di Francesco, A. Aguglia, Gaetano Catania, Carmen Concerto, A. Cuomo, Andrea Fagiolini, Giuseppe Lanza, Ludovico Mineo, A. Natale, L. Rapisarda, Antonino Petralia, M. Signorelli, Eugenio Aguglia
Frontiers in Psychiatry February 1, 2024 DOI: 10.3389/fpsyt.2024.1325399 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Overview of reviews Randomized Peer reviewed |
|---|---|
| Sample size | 3,316 |
| Population | Patients with unipolar or bipolar depression, including those with treatment-resistant and non-resistant depression, with and without suicidal ideation |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Citations | 28 |
| Key findings | Ketamine and esketamine appear effective and well-tolerated for treating major depressive episodes, but the evidence is of low certainty due to poor study quality. |
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).