Ketamine
Checked Oct 11, 2026 · 9 sources checked
Ketamine is an anesthetic. The FDA approved it as Ketalar in 1970, and its label covers anesthesia only. It is a Schedule III controlled drug. Ketamine is also studied for depression that has not improved with other treatments. In trials, a single infusion lowered depression scores within a day. In an early trial, though, only about a third of people still responded a week later. The FDA says ketamine is not approved for any psychiatric disorder. It lists risks including sedation, dissociation, higher blood pressure, slowed breathing, misuse and bladder problems. Since 2025 the Ketalar label also warns that repeated use, including supervised use for unapproved conditions, can injure the liver and bile ducts. In 2026 the FDA added warnings about bile-duct scarring and narrowing of the tubes that carry urine from the kidneys. A related drug, esketamine (Spravato), is FDA-approved for depression and has its own page.
Education only, not medical advice. Talk to a clinician about your own situation.
Ketamine draws steady, very high attention, though much of it is about anesthesia, misuse or news events rather than depression research. English Wikipedia's Ketamine article had 78,829 views in September 2026. PubMed added 49 records on ketamine and depression or suicidality in the 30 days to Oct 11 2026. Interest in at-home and telehealth ketamine prompted an FDA warning in 2023.
In adults with treatment-resistant depression, one ketamine infusion lowered depression scores more than an active placebo (midazolam) at 24 hours; 64% vs 28% responded.
For adults with treatment-resistant depression, is IV ketamine as effective as FDA-approved esketamine nasal spray?
If the equivalence trial NCT06713616 finds IV ketamine clearly less effective than esketamine, we would stop describing their short-term effects as similar.
If long-term data show frequent bladder injury or misuse with repeated clinic-based treatment, we would add that to the opening safety summary.
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In adults with treatment-resistant depression, one ketamine infusion lowered depression scores more than an active placebo (midazolam) at 24 hours; 64% vs 28% responded.
Adults with treatment-resistant major depression (73 randomized, two sites) · Outcome: MADRS change and response at 24 hoursConfidence applies to this claim and context.
Checked facts
- In adults with treatment-resistant depression, one ketamine infusion lowered depression scores more than an active placebo (midazolam) at 24 hours; 64% vs 28% responded. PMID 23982301 ↗
- An experimental oral prolonged-release ketamine tablet (KET01) did not beat placebo on the main depression measure at day 21 in 122 outpatients with treatment-resistant depression (difference 1.82 points, not significant), although earlier time points favored it. PMID 42340723 ↗
- In 156 hospitalized adults with suicidal ideation, more people on ketamine than on placebo had full remission of suicidal ideas at day 3 (63.0% vs 31.6%). The benefit was strongest in bipolar disorder, and by week 6 the difference was no longer significant (69.5% vs 56.3%). PMID 35110300 ↗
- In 186 hospitalized adults with unipolar depression, an open-label Swedish trial found that electroconvulsive therapy (ECT) led to remission more often than repeated ketamine infusions (63% vs 46%), so ketamine was inferior to ECT on this measure. Serious, lasting side effects such as memory loss were more common with ECT, while side effects led more people to drop out of ketamine treatment. Among people who remitted, most relapsed within 12 months in both groups (70% vs 63%). PMID 35020871 ↗
- In 403 adults referred for ECT (inpatients or outpatients) with treatment-resistant depression without psychosis, ketamine was noninferior to ECT over 3 weeks (response 55.4% vs 41.2%). ECT was linked to a temporary drop in memory recall; ketamine was linked to dissociation. The trial was open-label. PMID 37224232 ↗
- In a small early crossover trial (17 people treated with ketamine), ketamine improved depression scores within 110 minutes versus placebo; 71% responded the next day, but only about a third still met response criteria at one week. PMID 16894061 ↗
Attention describes reviewed public attention, evidence shows study types, and confidence applies only to the stated claim. There is no overall score.
Claims
Would change this claim: If the equivalence trial NCT06713616 finds IV ketamine clearly less effective than esketamine, we would stop describing their short-term effects as similar.
Source: Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. · PMID 23982301 · Am J Psychiatry · Abstract, Results: MADRS 7.95 points lower (95% CI 3.20-12.71); response 64% vs 28%; OR 2.18 · Verify ↗Mapped studies / experiment families
One experiment counts once, even with several registrations or publications. Counts above describe the headline claim.
No reviewed experiment families mapped yet.
Studies & active trials
Only papers and registered trials an editor reviewed for this page. Being listed is not a finding; the claims above say what they show.
What still isn't settled?
For adults with treatment-resistant depression, is IV ketamine as effective as FDA-approved esketamine nasal spray?
Ketamine and esketamine have mostly been tested in separate trials against different controls, so their results cannot be compared directly. A head-to-head equivalence trial is recruiting.
What would answer it: Primary results of the PCORI-funded esketamine vs ketamine equivalence trial (NCT06713616; 400 participants; est. primary completion 2030-12).
Shown in randomized trials: a single ketamine infusion can reduce depression scores within 24 hours in people with treatment-resistant depression, including against an active placebo. Two open-label trials compared it with electroconvulsive therapy (ECT) and disagreed: in patients referred for ECT it was not worse, but in hospitalized patients ECT led to remission more often. How long the benefit lasts, and long-term safety with repeated use, are not settled.