Ketamine Infusion Shows Rapid Reduction in Suicidal and Depressive Symptoms, New Analysis Finds

A new analysis of multiple studies suggests that ketamine infusions can quickly reduce suicidal thoughts and depression symptoms in people experiencing a major depressive episode. The findings come from a systematic review and meta-analysis published in JAMA Psychiatry.

Researchers looked at 26 randomized trials that included more than 1,100 patients. They found that patients who received a single ketamine infusion showed a significant drop in suicidal symptoms compared with a control group at two key time points: 24 hours after treatment and again at one month. Those who received repeated ketamine infusions also had a similar reduction in suicidal symptoms by the end of their treatment.

For depressive symptoms, the results were also notable. Patients who got a single ketamine infusion had significant reductions in depression at several time points, including 4 hours, 24 hours, 3 days, and 1 week after treatment. Those who received repeated infusions also showed significant improvement by the end of treatment.

The study was led by Taeho Greg Rhee, PhD, of the University of Connecticut School of Medicine in Farmington, and his team. They highlighted what these findings could mean for real-world care. “Given that the rapid antisuicidal effects occurred within the first 4 hours after a single infusion and remained effective at 24 hours, intravenous ketamine may potentially be used in emergency treatment for those at high risk of suicidal behaviors,” they wrote.

They also noted that patients with treatment-resistant depression are likely to need repeated infusions rather than just one. That is because the effects of a single ketamine infusion are often short-lived. According to the researchers, nearly all patients saw their depressive symptoms return within two weeks after a single dose.

However, the authors pointed out that long-term safety data on ketamine are scarce. Ketamine is not approved by the U.S. Food and Drug Administration (FDA) for depression, but it is often used off-label. The researchers said more studies are needed to look at potential risks, including cognitive impairment and the drug’s potential for abuse. A related product, esketamine nasal spray (brand name Spravato), is FDA-approved for treatment-resistant depression and for major depressive disorder with suicidal thoughts. It is used together with an oral antidepressant.

Martin Plöderl, PhD, of the Christian Doppler Clinic at Paracelsus Medical University in Salzburg, Austria, was not involved in the study. He called the effects “clinically meaningful and larger than conventional antidepressants.” But he also raised concerns. He told MedPage Today that most of the studies included in the analysis were small, and “some have implausibly large effects. This is a red flag.”

Blinding was also a concern in some of the trials. Blinding means that patients and researchers do not know who is getting the real treatment versus a placebo. Declan McLoughlin, PhD, of Trinity College Dublin, noted that in his team’s recent trial, “the vast majority of patients and raters correctly guessed the allocated treatment.” He explained that “unblinding contributes to expectancy bias and thereby skews the true treatment effect.” Despite the excitement around ketamine, he pointed out that large community-based studies reflecting real-world practice “have not been so promising.”

For this meta-analysis, Rhee and his team searched four major research databases—PubMed, PsycInfo, Cochrane Library, and Embase—from their start dates through November 7, 2025. They included only randomized trials where participants had a diagnosis of a major depressive episode. The intervention group received intravenous ketamine, and the control group received either saline or midazolam. The studies had to report on suicidal and depressive symptoms as outcomes.

Across the 26 trials, 626 patients received ketamine and 540 served as controls. About 69% of the trials used a single ketamine infusion, while the rest used repeated infusions. Most of the trials—80.8%—included patients with major depressive disorder. About 11.5% included patients with bipolar depression, and 7.7% included patients with both unipolar and bipolar depression.

Ketamine also showed better response rates for depressive symptoms at 4 hours, 24 hours, 3 days, and 1 week after a single infusion. However, response rates were not significantly better after repeated infusions. Ketamine did not show a significant difference in remission rates.

Ten studies reported serious adverse events, including hospitalizations, suicide attempts, non-suicide-related deaths, suicide, or other medical conditions. The researchers said most of these events were not related to the treatments. The most common side effects in the ketamine groups included headache, cardiorespiratory issues, numbness, tingling, dissociation, nausea, dizziness, and visual disturbances. These symptoms usually resolved within a few hours after the infusion.

Source: MedPage Today