Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis.
Sung Ryul Shim, Hye Su Jeong, Tanner J. Bommersbach, Andrew A. Nierenberg, Carlos A. Zarate, Tyler S Kaster, Christoph U Correll, Roger S McIntyre, John H. Krystal, Taeho Greg Rhee
JAMA Psychiatry July 1, 2026 DOI: 10.1001/jamapsychiatry.2026.0612 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 1,166 |
| Population | Patients with a major depressive episode |
| Intervention | Intravenous ketamine |
| Topics | Esketamine Ketamine |
| Citations | 1 |
| Key findings | Single and repeated intravenous ketamine infusions are efficacious in reducing suicidal and depressive symptoms in patients with a major depressive episode during the acute phase. |
Abstract
While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms. To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs). PubMed, PsycInfo, Cochrane Library, and Embase were systematically searched from database inception through November 7, 2025, with no language limits. Randomized clinical trials (RCTs) with (1) diagnosis of an MDE; (2) intervention and comparator groups consisting of intravenous ketamine and controls (eg, saline or midazolam); and (3) suicidal and depressive symptoms as efficacy outcomes were included. Hedges g standardized mean differences (SMDs) were used to analyze improvement in suicidal and depressive symptoms using random-effects models. Multiple subgroup analyses were also conducted. The main outcomes included the following: (1) changes in suicidal and depressive symptoms; (2) response and remission rates of depressive symptoms; and (3) safety measures (eg, adverse events and serious adverse events). A total of 26 RCTs comprising 1166 patients with an MDE (n = 626 receiving ketamine and n = 540 as control patients) were included. For suicidal symptoms, patients receiving a single ketamine infusion, compared with control patients, had significantly lower symptoms at 24 hours (SMD, -0.69 [95% CI, -0.98 to -0.40]) and at 1 month (SMD, -0.70 [95% CI, -1.17 to -0.24]). Those with repeated ketamine infusions showed a similar reduction of suicidal symptoms at the end of the treatment (SMD, -0.72 [95% CI, -1.00 to -0.43]). For depressive symptoms, significant reductions were shown at 4 hours (SMD, -1.74 [95% CI, -2.43 to -1.06]), 24 hours (SMD, -1.15 [95% CI, -1.58 to -0.72]), 3 days (SMD, -0.97 [95% CI, -1.73 to -0.20]), and 1 week (SMD, -0.89 [95% CI, -1.65 to -0.13]) after a single ketamine infusion and at the end of the treatment after repeated infusions (SMD, -0.81 [95% CI, -1.16 to -0.46]). Reported serious adverse events (eg, hospitalizations and deaths) were unrelated to the interventions, and other adverse events (eg, headache) were transient and resolved during the trials. The findings of this systematic review and meta-analysis suggest that single and repeated intravenous ketamine infusions are efficacious in reducing suicidal and depressive symptoms in patients with an MDE in the acute phase, while longer-term outcomes are not well established.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 3
- Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy Journal of Affective Disorders August 10, 2026
- From psychache to neuroplasticity: A unified rescue-repair model of Ketamine's anti-suicidal action. Neuroscience & Biobehavioral Reviews June 7, 2026
- Symptom-level and network analyses of ketamine treatment in treatment-resistant depression: A pooled analysis of two randomized controlled trials. Progress in neuro-psychopharmacology & biological psychiatry September 26, 2026
Cites 39
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
and 34 more in the library