Comparative efficacy and safety of intravenous racemic ketamine, repetitive transcranial magnetic stimulation and electroconvulsive therapy for Stage 2 or higher treatment-resistant depression: A systematic review and network meta-analysis.
Itsuki Terao, Takahiro Tsuge, Tomoo Sato, Kaori Endo, Kazumasa Kotake, Masahiro Banno, Yuki Kataoka
Psychiatry and Clinical Neurosciences Reports September 1, 2025 DOI: 10.1002/pcn5.70136 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and network meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 2,109 |
| Population | Adults with treatment-resistant depression |
| Interventions | Electroconvulsive therapy Intravenous racemic ketamine Repetitive transcranial magnetic stimulation |
| Topics | Depression Ketamine Esketamine |
| Keywords | Network meta‐analysis Transcranial magnetic stimulation Treatment resistance Network meta-analysis Ketamine therapy |
| Citations | 2 |
| Key findings | Intravenous ketamine and rTMS did not show inferiority to ECT in antidepressant efficacy or safety, and ketamine had higher acceptability, but the evidence was rated as very low confidence. |
Abstract
Although electroconvulsive therapy (ECT) is the standard treatment for Stage 2 or higher treatment-resistant depression, it has several drawbacks. Repetitive transcranial magnetic stimulation (rTMS) and intravenous racemic ketamine (IV ketamine) have emerged as potential alternatives, but their comparative effectiveness and safety remain unclear due to limited evidence. We systematically searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and trial registries for randomized controlled trials (RCTs) up to 18 December 2023. Random-effects network meta-analyses were performed to compare the antidepressant efficacy, tolerability, and acceptability of ECT, IV ketamine, and rTMS. Thirty-five RCTs (n = 2109) were included. Most of the included studies had small sample sizes. There were no significant differences in response rate, remission rate, or tolerability of IV ketamine, rTMS, and ECT, while IV ketamine had significantly higher acceptability compared to rTMS and ECT. The confidence in the evidence for efficacy, tolerability, and acceptability was very low. IV ketamine and rTMS did not demonstrate apparent inferiority to ECT in terms of antidepressant efficacy and safety. Considering the various drawbacks of ECT, both treatments may have the potential to serve as viable alternatives. However, the confidence of the evidence in this study is rated as very low, possibly due to small-study bias, highlighting the need for further large-scale studies to strengthen the findings.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.
Citations in the library
Cited by 2
- Ketamine Combined With Psychotherapy as a Treatment for Resistant Depression in a Public European Hospital. Brain and Behavior 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
Cites 11
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal of Medicine May 24, 2023
- Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial. Journal of Affective Disorders 2019
- Long-term safety of ketamine and esketamine in treatment of depression Expert Opinion on Drug Safety April 13, 2022
- Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT) The International Journal of Neuropsychopharmacology December 4, 2021
and 6 more in the library