Meta-analysis · 2026
Pooled analysis of 26 trials: IV ketamine rapidly lowers depression and suicidal symptoms
- Original title
- Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis.
- Authors
- Shim SR, Jeong HS, Bommersbach TJ, et al.
- Journal
- JAMA psychiatry, 2026
- Molecules
- Ketamine
- Conditions
- Depression, Suicidal ideation
- Participants
- 1166
- Evidence grade
- Moderate
- Source
- Read the original paper
The question
Does intravenous ketamine reduce suicidal thoughts and depressive symptoms in people going through a major depressive episode, and is it safe in the short term?
What they did
Researchers searched four large research databases from their beginning through November 7, 2025, with no language limits. They included only randomized controlled trials that compared intravenous ketamine with a control such as saline or midazolam in people diagnosed with a major depressive episode. Results from 26 trials, covering 1166 patients (626 given ketamine and 540 given a control), were pooled statistically.
What they found
After a single ketamine infusion, suicidal symptoms were lower than in control groups at 24 hours (standardized mean difference -0.69, 95% CI -0.98 to -0.40) and at 1 month (-0.70, 95% CI -1.17 to -0.24). Repeated infusions showed a similar reduction in suicidal symptoms by the end of treatment (-0.72, 95% CI -1.00 to -0.43). Depressive symptoms dropped at 4 hours (-1.74), 24 hours (-1.15), 3 days (-0.97) and 1 week (-0.89) after a single infusion, and at the end of treatment after repeated infusions (-0.81). Serious adverse events such as hospitalizations and deaths were judged unrelated to the treatments, and other side effects such as headache were short-lived and resolved during the trials.
The fine print
The pooled trials were mostly small, and the confidence ranges around several results were wide, meaning the true size of the benefit is uncertain. Ketamine produces noticeable effects that can make blinding difficult, so participants and raters may have guessed who received it. The authors state that longer-term outcomes are not well established, and this summary is based on the abstract only.
What it means
Across the randomized evidence to date, intravenous ketamine appears to reduce suicidal and depressive symptoms quickly in people in a major depressive episode, but how long those gains last remains unclear.
Evidence grade: Moderate. A meta-analysis of 26 randomized controlled trials with consistent results, but the individual trials were small, effect estimates had wide ranges, and keeping ketamine trials properly blinded is difficult.
This summary is based on the study’s published abstract.