Intravenous Ketamine infusions effective for reducing Acute Suicidal and Depressive Symptoms: JAMA

For the purposes of creating a precise overview of ketamine’s effect on patients, a meta-analysis was performed on prominent medical databases such as PubMed, PsycInfo, Cochrane Library, and Embase, with an inception-to-November 7, 2025 search strategy. Specifically, RCTs with inclusion criteria such as a diagnosis of MDE, the use of intravenous ketamine in relation to other treatments (active or placebo control conditions like saline and midazolam), and suicidal and depressive symptomatology as primary efficacy outcomes were considered. In order to integrate data obtained from clinical scales in this manner, the investigators computed SMDs using Hedges g formulae via the random effects model, which allows for heterogeneity among clinical studies. The secondary outcomes included clinical response/remission rates, in addition to stringent safety parameters, involving transient adverse events and serious adverse events.

Key findings:

• The meta-analysis included studies on 26 high-quality RCTs with a total number of 1,166 patients having an MDE, with 626 patients receiving IV ketamine and 540 being control patients.
• Within 24 hours following a single dose of ketamine, patients showed significantly decreased levels of suicidality as opposed to controls (SMD, −0.69 [95% CI, −0.98 to −0.40]), and also showed decreased levels of suicidality within a month after the infusion (SMD, −0.70 [95% CI, −1.17 to −0.24]).
• Repeated dosing resulted in similar outcomes at the end of the dosing period (SMD, −0.72 [95% CI, −1.00 to −0.43]).
• In case of a single infusion, the depression symptoms reduced remarkably within 4 hours (SMD, −1.74 [95% CI, −2.43 to −1.06]), within 24 hours (SMD, −1.15 [95% CI, −1.58 to −0.72]), within 3 days (SMD, −0.97 [95% CI, −1.73 to −0.20]), and within a week (SMD, −0.89 [95% CI, −1.65 to −0.13]), while with repeated infusions, the SMD was found to be −0.81 (95% CI, −1.16 to −0.46) at the end of treatment.
• Reported serious adverse events, including hospitalizations and deaths, were determined to be entirely unrelated to the ketamine intervention, and common side effects, such as transient headaches, resolved rapidly without medical intervention.

The conclusions drawn from this systematic review and meta-analysis clearly indicate that both single and multiple infusions of ketamine intravenously are very effective in alleviating symptoms of suicidality and depression in patients with an MDE during the acute phase, but their long-term efficacy remains unclear. For the psychiatry field, these strong results confirm the effectiveness of the off-label use of ketamine as an effective intervention that will quickly help patients in the acute phase of depression or suicidality. However, since the effects of ketamine decay quickly, it must be used as a bridge therapy and not as a long-term therapy.

Reference:

Shim SR, Jeong HS, Bommersbach TJ, et al. Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis. JAMA Psychiatry. Published online May 06, 2026. doi:10.1001/jamapsychiatry.2026.0612