Single Ketamine Infusion Rapidly Eases Severe Depression, Study Finds

A single intravenous infusion of ketamine can significantly reduce severe depression symptoms within hours and dramatically lower suicidal thoughts for up to a month, according to a comprehensive new meta-analysis published in JAMA Psychiatry. The findings offer a potential lifeline for the millions of patients with treatment-resistant depression who do not respond to conventional antidepressants.

The Study at a Glance

Researchers led by Dr. Taeho Greg Rhee of the University of Connecticut School of Medicine analyzed 26 randomized controlled trials involving more than 1,100 patients. Of the participants, 626 received ketamine infusions while 540 served as controls receiving saline or midazolam. The results, published May 6, showed that a single infusion produced measurable improvements in depressive symptoms within just four hours — a stark contrast to traditional antidepressants, which can take weeks to take effect.

According to MedPage Today, patients who received ketamine showed significant reductions in depressive symptoms at four hours, 24 hours, three days, and one week after a single infusion. Suicidal thoughts dropped dramatically within 24 hours, with effects persisting for up to a month.

A Rapid Alternative for Treatment-Resistant Patients

Major depressive disorder affects approximately 280 million people globally. At least one-third of adults with depression do not respond to two or more conventional antidepressant therapies, a condition known as treatment-resistant depression. These patients face a heightened risk of suicidal thoughts, suicide attempts, and death.

“When all existing treatment options fail, patients with severe depression could consider ketamine infusions,” Rhee told Fox News. “This is still a safer option when compared to electroconvulsive therapy (ECT).”

Dr. Lama Bazzi, a psychiatrist in New York City who was not involved in the study, described ketamine’s potential in stark terms: “For a small subset of patients in a major depressive episode or struggling with suicidal thoughts, intravenous ketamine can be genuinely lifesaving. The relief they experience is almost immediate, offering them distance from the intensity of their emotions.”

How Ketamine Works

Unlike traditional antidepressants — which stabilize mood by slowly elevating serotonin levels — ketamine works rapidly by blocking glutamate, a neurotransmitter that can negatively impact emotions when present at high levels in the brain. Originally developed as a fast-acting surgical anesthetic in the 1960s, ketamine has increasingly been used off-label for treatment-resistant depression in recent years.

However, the drug’s history as a recreational substance known as “Special K” has contributed to its controversial reputation. Experts emphasize that ketamine should only be administered in closely monitored clinical settings.

Limitations and Cautions

Despite the promising results, researchers and independent experts urge caution. The effects of a single infusion are short-lived — nearly all patients relapsed within two weeks, indicating that repeated sessions would be necessary for sustained benefit.

Martin Plöderl, PhD, of the Christian Doppler Clinic in Austria, who was not involved in the study, called the effects “clinically meaningful and larger than conventional antidepressants” but noted that most studies were small and “some have implausibly large effects. This is a red flag,” he told MedPage Today.

Declan McLoughlin, PhD, of Trinity College Dublin, raised concerns about unblinding bias, noting that in his team’s recent trial, “the vast majority of patients and raters correctly guessed the allocated treatment,” which can skew results through expectancy bias.

Common side effects — including headache, numbness, dissociation, nausea, dizziness, and visual disturbances — were temporary and resolved within hours. Rarer serious events included hospitalization and suicide attempts, but most were assessed as unrelated to ketamine.

FDA Status and Access

Intravenous ketamine is not yet FDA-approved for treating depression and is used off-label. However, a related product — esketamine (Spravato) — is FDA-approved as a nasal spray for treatment-resistant depression and major depressive disorder with suicidal ideation. Rhee noted that while IV ketamine lacks formal FDA approval, “it may still be used with off-label indications for those with severe depression and/or with a high risk of suicidal behaviors.”

What’s Next

Rhee and colleagues plan to conduct population-level epidemiologic studies to further examine the effectiveness and safety profiles of ketamine treatment. Meanwhile, a separate study from Stanford University, published May 19 in the American Journal of Psychiatry, found that combining low-dose buprenorphine with ketamine infusion extended anti-suicidal effects to four weeks — achieving a 76% reduction in suicidal ideation compared to 43% with placebo, as reported by ScienMag.

As research accelerates, ketamine and its derivatives may increasingly become part of the psychiatric toolkit — but experts agree that rigorous safety monitoring and further long-term studies remain essential.

Anyone experiencing suicidal thoughts or severe depression should consult a healthcare provider or call the Suicide and Crisis Lifeline at 988.