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The Impact of Ketamine-Based Versus Non-Ketamine-Based ECT Anesthesia Regimens on the Severity of Patients’ Depression and Occurrence of Adverse Events: A Systematic Review with Meta-Analysis

Dakota Sicignano, Rohan Kantesaria, Matthew Mastropietro, Ava Sedensky, Roslyn Kohlbrecher, Adrían V. Hernández, C. Michael White

Annals of Pharmacotherapy March 1, 2025 DOI: 10.1177/10600280241260754 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and meta-analysis Randomized Peer reviewed
Sample size 1,181
Population Patients with treatment-resistant depression undergoing electroconvulsive therapy
Interventions Ketamine Electroconvulsive therapy (ECT)
Measures Hamilton Depression Rating Scale (HAM-D), Montgomery-Asburg Depression Rating Scale (MADRS)
Topics Depression Esketamine Ketamine
Key findings Ketamine anesthesia during ECT was associated with greater clinical remission (OR 1.78, 95% CI 1.08-2.93) and lower HAM-D scores after the third through sixth and eighth ECT sessions compared with nonketamine anesthesia, but also with significantly more fear with hallucinations (OR 1.99, 95% CI 1.11-3.58). The authors conclude ketamine is a promising adjunct that may enhance antidepressant effects in exchange for more adverse events, with the benefit-harm balance unclear.

Abstract

Objective: To compare efficacy and safety outcomes for ketamine anesthesia + electroconvulsive therapy (ECT) versus nonketamine anesthesia + ECT in treatment-resistant depression (TRD) patients. Data Sources: PubMed and Embase were searched from the earliest date through November 27, 2023. Study Selection and Data Extraction: Relevant randomized controlled trials (RCTs) of ketamine + ECT versus nonketamine anesthesia + ECT that reported data on remission (odds ratio [OR]), defined as a Hamilton Depression Rating Scale (HAM-D) and Montgomery-Asburg Depression Rating Scale (MADRS) score <8-10) and mean differences (MDs) in HAM-D scores after several ECT sessions were compared using inverse variance methods. The risk of bias (RoB) was assessed using the Cochrane RoB tool. Data Synthesis: Seventeen RCTs (RoB: Low N = 12, Moderate N = 2, High N = 3) with 1181 total patients met inclusion criteria. Patients receiving ECT experienced greater clinical remission (OR: 1.78, [95% confidence interval (CI): 1.08-2.93], I 2 = 11%, N = 9) and lower HAM-D scores after the third through sixth ECT sessions as well as the eighth ECT session when ketamine versus nonketamine anesthesia was used. Ketamine use with ECT significantly increased fear with hallucinations (OR: 1.99, [95% CI: 1.11-3.58], I 2 = 0%, N = 7) than with nonketamine anesthesia. Relevance to Patient Care and Clinical Practice: Selecting ketamine-based anesthesia could more quickly and profoundly enhance the beneficial effects of ECT for patients with severe TRD, but the balance of benefits to harm is unclear as there may be additional adverse events.

Conclusion: Ketamine is a promising anesthesia adjunct to ECT that may enhance antidepressant effects in exchange for more adverse events.