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 hours
Confidence applies to this claim and context.
AttentionNot assessedNo current independent attention assessment
EvidenceNo mapped studiesNo reviewed experiment families currently mapped
ConfidenceNot assessedFor: 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.. No current reviewed confidence assessment for this claim.
The GapAttention not measured
Attention describes reviewed public attention, evidence shows study types, and confidence applies only to the stated claim. There is no overall score.
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Why we checked it
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.
Here's where it actually stands
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.
What we know
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.
What we don't know
For adults with treatment-resistant depression, is IV ketamine as effective as FDA-approved esketamine nasal spray?
Claims
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. · headlineAdults with treatment-resistant major depression (73 randomized, two sites) · Outcome: MADRS change and response at 24 hoursConfidence: Not assessed · source checked
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 ↗
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.Adult outpatients with treatment-resistant depression (29 sites, Europe) · Outcome: MADRS change at day 21Confidence: Not assessed · source checkedSource: Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials. · PMID 42340723 · JAMA Netw Open · Abstract, Results: primary end point not met, LS mean difference -1.82 (95% CI -6.21 to 2.57), P=.41; nominal differences at day 4 and day 7 · Verify ↗
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%).Adults admitted voluntarily with current suicidal ideation (7 French hospitals) · Outcome: Full remission of suicidal ideasConfidence: Not assessed · source checkedSource: Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. · PMID 35110300 · BMJ · Abstract, Results, quoted as printed: "46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm"; OR 3.7 (1.9-7.3); week 6 69.5% vs 56.3%, OR 0.8 (0.3-2.5) · Verify ↗Source: Effects of Ketamine in the Acute Phase of Suicidal Ideation · NCT NCT02299440 · Centre Hospitalier Universitaire de Nīmes · Abstract, Results, quoted as printed: "46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm"; OR 3.7 (1.9-7.3); week 6 69.5% vs 56.3%, OR 0.8 (0.3-2.5) · Verify ↗
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%).Hospitalized adults with unipolar depression (Sweden) · Outcome: Remission (MADRS); adverse events; relapseConfidence: Not assessed · source checkedSource: Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT). · PMID 35020871 · Int J Neuropsychopharmacol · Abstract, Results: 186 inpatients; remission 63% vs 46% (P=.026; difference 95% CI 2%-30%); relapse 70% vs 63% (P=.52) · Verify ↗
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.Inpatients or outpatients referred for ECT with nonpsychotic treatment-resistant depression · Outcome: Response (QIDS-SR-16) at end of 3-week phaseConfidence: Not assessed · source checkedSource: Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. · PMID 37224232 · N Engl J Med · Abstract, Results: response 55.4% vs 41.2%; difference 14.2 points (95% CI 3.9-24.2); memory recall T-score -0.9 vs -9.7 · Verify ↗Source: ELEKT-D: Electroconvulsive Therapy (ECT) vs. Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) · NCT NCT03113968 · Bo Hu · Abstract, Results: response 55.4% vs 41.2%; difference 14.2 points (95% CI 3.9-24.2); memory recall T-score -0.9 vs -9.7 · Verify ↗
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.Adults with treatment-resistant major depression (18, NIMH unit) · Outcome: HDRS change; responseConfidence: Not assessed · source checkedSource: A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. · PMID 16894061 · Arch Gen Psychiatry · Abstract, Results: effect size d=1.46 at 24 h; 71% response, 29% remission day 1; 35% maintained response at 1 week · Verify ↗
Mapped studies / experiment families
One experiment counts once, even with several registrations or publications. Counts above describe the headline claim.
Mar 23, 2026Label safety update, S-057: sclerosing cholangitis; ureteral stenosis and obstruction.U.S. FDA (Drugs@FDA) ↗
Only papers and registered trials an editor reviewed for this page. Being listed is not a finding; the claims above say what they show.
Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials.PMID 42340723 · DOI 10.1001/jamanetworkopen.2026.19121Study · Published · Jun 1, 2026 · JAMA Netw OpenOpen source ↗
Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.PMID 37224232 · DOI 10.1056/NEJMoa2302399Study · Published · Jun 22, 2023 · N Engl J MedOpen source ↗
Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT).PMID 35020871 · DOI 10.1093/ijnp/pyab088Study · Published · May 27, 2022 · Int J NeuropsychopharmacolOpen source ↗
Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial.PMID 35110300 · DOI 10.1136/bmj-2021-067194Study · Published · Feb 2, 2022 · BMJOpen source ↗
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.PMID 23982301 · DOI 10.1176/appi.ajp.2013.13030392Study · Published · Am J PsychiatryOpen source ↗
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.PMID 16894061 · DOI 10.1001/archpsyc.63.8.856Study · Published · Arch Gen PsychiatryOpen source ↗
ELEKT-D: Electroconvulsive Therapy (ECT) vs. Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D)NCT NCT03113968Trial · Completed · Sep 28, 2023 · Bo HuOpen registry record ↗
Effects of Ketamine in the Acute Phase of Suicidal IdeationNCT NCT02299440Trial · Completed · Centre Hospitalier Universitaire de NīmesOpen registry record ↗
What would change our mind
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.
Effects of Ketamine in the Acute Phase of Suicidal IdeationCentre Hospitalier Universitaire de Nīmes · checked Oct 11, 2026 · NCT NCT02299440; status:COMPLETED
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.Am J Psychiatry · checked Oct 11, 2026 · PMID 23982301; DOI 10.1176/appi.ajp.2013.13030392
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.Arch Gen Psychiatry · checked Oct 11, 2026 · PMID 16894061; DOI 10.1001/archpsyc.63.8.856
Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial.BMJ · checked Oct 11, 2026 · PMID 35110300; DOI 10.1136/bmj-2021-067194
Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.N Engl J Med · checked Oct 11, 2026 · PMID 37224232; DOI 10.1056/NEJMoa2302399
Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials.JAMA Netw Open · checked Oct 11, 2026 · PMID 42340723; DOI 10.1001/jamanetworkopen.2026.19121
Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT).Int J Neuropsychopharmacol · checked Oct 11, 2026 · PMID 35020871; DOI 10.1093/ijnp/pyab088
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.
Is repeated ketamine safe over months, especially for the bladder and for misuse?The randomized trials above lasted days to weeks. FDA lists bladder symptoms and misuse among concerns for psychiatric use, and the Ketalar label now warns of liver, bile-duct and urinary-tract injury with repeated or long-term use, based on reports rather than controlled studies, but there are no long-term controlled data for repeated low-dose use.What would answer it: Long-term (12 months or more) controlled or registry data reporting urinary, cognitive and misuse outcomes with repeated treatment.