Research
Ketamine Research Library
A curated library of landmark and recent peer-reviewed studies by condition, plus articles, videos, and podcasts from major universities and health agencies.
This library brings together peer-reviewed studies from journals including the New England Journal of Medicine (NEJM), JAMA Psychiatry, and the American Journal of Psychiatry. Last reviewed October 2026. This page is for education and is not medical advice.
Latest Research by Condition (Last 10 Years)
Recent randomized trials, meta-analyses, and reviews, including results that were mixed or negative, so you see the full picture.
Depression
New England Journal of Medicine (PubMed) · 2023
Ketamine versus ECT for nonpsychotic treatment-resistant major depression
403-person trial: ketamine was not less effective than ECT for short-term response.
Read sourceNew England Journal of Medicine (PubMed) · 2023
Esketamine nasal spray versus quetiapine for treatment-resistant depression
676-person trial of Spravato vs an established medication strategy.
Read sourcePubMed · 2026
Oral ketamine for major depressive and bipolar disorder: RCT and meta-analysis
Looks at whether tablets could widen access beyond infusion centers.
Read sourceJAMA Network (PubMed) · 2025
Serial ketamine infusions as adjunctive inpatient care (KARMA-Dep 2)
A balanced result: no significant difference vs active placebo in hospitalized patients.
Read sourceSuicidal Thoughts
PubMed · 2026
Ketamine infusions and rapid reduction of suicidal and depressive symptoms: meta-analysis
26 randomized trials, 1,166 patients; lower suicidal symptoms at 24 hours and 1 month.
Read sourcePubMed · 2026
Low-dose buprenorphine following ketamine for suicidal ideation
Stanford-led trial testing a way to extend ketamine's effect.
Read sourcePTSD
American Journal of Psychiatry (PubMed) · 2021
Repeated ketamine administration for chronic PTSD (randomized trial)
First RCT of repeated infusions for chronic PTSD; Mount Sinai and Yale researchers.
Read sourcePubMed Central · 2025
Effects of intravenous ketamine on PTSD: a systematic review
Seven studies, 323 participants; repeated schedules showed greater benefit.
Read sourceAnxiety, OCD & Substance Use
PubMed · 2024
Ketamine for psychiatric disorders: systematic review and meta-analysis
Supports potential use in PTSD, OCD and alcohol use disorder; evidence still limited.
Read sourcePubMed Central · 2021
Ketamine RCTs in refractory anxiety spectrum disorders: meta-analysis
Social anxiety, PTSD and OCD trials reviewed together.
Read sourceArticles from Universities & Health Agencies
Yale School of Medicine · 2026
Ketamine: How Yale Redefined Depression Treatment
The story of the discovery, from the researchers who made it.
Read sourceYale Medicine · 2024
Ketamine for Depression: How It Works
Plain-language explainer on who may be a candidate.
Read sourceNational Institute of Mental Health (NIH) · 2024
New Hope for Rapid-Acting Depression Treatment
NIMH update on a ketamine-related compound.
Read sourceNational Institute of Mental Health (NIH) · 2023
Cracking the Ketamine Code
How NIH research is explaining why ketamine works so fast.
Read sourceStanford Medicine · 2026
Drug combo is the first to prolong ketamine's antisuicide effects
Stanford trial news release.
Read sourceCleveland Clinic · 2020
Ketamine for Treatment-Resistant Depression: A Better Alternative to ECT?
Dr. Amit Anand, lead author of the 2023 NEJM trial.
Read sourceMassachusetts General Hospital · 2019
What to Know About Esketamine and Ketamine Treatment
Q&A on the difference between ketamine and Spravato.
Read sourceExpert Videos
Good Morning America (ABC News) · 2023
What You Need to Know About Ketamine Therapy
View original sourcePodcasts
Psychiatry & Psychotherapy Podcast · 2022
Ketamine Update with Brandon Kitay, MD (Ep. 137)
Former Yale esketamine trial researcher on how treatment works in practice.
View original episodeCleveland Clinic Consult QD · 2020
Ketamine for TRD: A Better Alternative to ECT?
Audio interview with Dr. Amit Anand. The publisher's current player is titled ‘Ketamine Research for Treatment-Resistant Depression (Early Work Through Current State).’
View original episodePsychiatry & Psychotherapy Podcast · 2018
Ketamine and Psychedelics with Dr. Michael Cummings (Ep. 30)
Balanced look at benefits and risks.
View original episodeLandmark Studies by Condition
Treatment-Resistant Depression
The strongest body of evidence. Randomized trials since 2000 show rapid antidepressant effects, often within 24 hours, including in people who have not responded to two or more medications. Recent head-to-head trials compare ketamine favorably with ECT, and esketamine with an established medication strategy.
Biological Psychiatry · 2000
Antidepressant effects of ketamine in depressed patients
Berman RM, Cappiello A, Anand A, et al.
Design: Randomized, double-blind, placebo-controlled crossover
Key finding: First controlled trial showing a single low-dose ketamine infusion significantly reduced depressive symptoms within 72 hours.
View on PubMedArchives of General Psychiatry · 2006
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression
Zarate CA Jr, Singh JB, Carlson PJ, et al.
Design: Randomized, placebo-controlled crossover (NIMH)
Key finding: Robust antidepressant response within 2 hours in treatment-resistant depression, lasting about one week for many participants.
View on PubMedAmerican Journal of Psychiatry · 2013
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial
Murrough JW, Iosifescu DV, Chang LC, et al.
Design: RCT with active placebo (midazolam), n=73
Key finding: Response at 24 hours was 64% with ketamine vs 28% with midazolam, addressing concerns about blinding.
View on PubMedNew England Journal of Medicine · 2023
Ketamine versus ECT for nonpsychotic treatment-resistant major depression
Anand A, Mathew SJ, Sanacora G, et al.
Design: Open-label randomized noninferiority trial (ELEKT-D), n=403
Key finding: Ketamine was noninferior to electroconvulsive therapy, with fewer memory-related side effects.
View on PubMedNew England Journal of Medicine · 2023
Esketamine nasal spray versus quetiapine for treatment-resistant depression
Reif A, Bitter I, Buyze J, et al.
Design: Randomized open-label, rater-blinded trial (ESCAPE-TRD), n=676
Key finding: Esketamine produced higher remission rates at week 8 than extended-release quetiapine.
View on PubMedAmerican Journal of Psychiatry · 2019
Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study
Popova V, Daly EJ, Trivedi M, et al.
Design: Phase 3 RCT (TRANSFORM-2)
Key finding: Pivotal trial supporting FDA approval of esketamine (Spravato) for treatment-resistant depression.
View on PubMedJAMA Psychiatry · 2019
Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial
Daly EJ, Trivedi MH, Janik A, et al.
Design: Randomized withdrawal trial (SUSTAIN-1)
Key finding: Continued esketamine reduced relapse risk by about 51% among patients in stable remission.
View on PubMedAmerican Journal of Psychiatry · 2021
Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation
McIntyre RS, Rosenblat JD, Nemeroff CB, et al.
Design: International expert consensus review
Key finding: Concludes ketamine and esketamine have rapid, clinically meaningful effects and outlines best practices for safe delivery.
View on PubMedSuicidal Thoughts
Ketamine is one of very few treatments shown to reduce suicidal thoughts within hours. It is not a substitute for emergency care. If you are in crisis, call or text 988.
American Journal of Psychiatry · 2018
The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis
Wilkinson ST, Ballard ED, Bloch MH, et al.
Design: Individual participant meta-analysis, 10 trials
Key finding: Ketamine rapidly reduced suicidal ideation within one day, with benefits lasting up to one week, partly independent of mood improvement.
View on PubMedAmerican Journal of Psychiatry · 2018
Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial
Grunebaum MF, Galfalvy HC, Choo TH, et al.
Design: RCT vs midazolam, n=80
Key finding: Significantly greater reduction in suicidal ideation at 24 hours with ketamine.
View on PubMedPTSD
Controlled trials show ketamine can reduce core PTSD symptoms, including intrusive memories and avoidance. Results are encouraging but studies remain smaller than those for depression.
JAMA Psychiatry · 2014
Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial
Feder A, Parides MK, Murrough JW, et al.
Design: Randomized midazolam-controlled crossover
Key finding: Single infusion produced rapid reduction in PTSD symptom severity at 24 hours.
View on PubMedAmerican Journal of Psychiatry · 2021
A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder
Feder A, Costi S, Rutter SB, et al.
Design: RCT, six infusions over two weeks
Key finding: 67% of ketamine participants responded vs 20% with midazolam; improvement lasted a median of about four weeks.
View on PubMedContemporary Clinical Trials · 2019
Repeated ketamine infusions for antidepressant-resistant PTSD: methods of a multicenter, randomized, placebo-controlled clinical trial
Abdallah CG, Roache JD, Averill LA, et al.
Design: Multicenter trial protocol (veterans and service members)
Key finding: Describes the design of a Department of Defense–funded trial testing dosing in military PTSD.
View on PubMedAnxiety Disorders
Smaller trials suggest ketamine may reduce symptoms of social anxiety and treatment-resistant generalized anxiety. Evidence is emerging and larger studies are ongoing.
Neuropsychopharmacology · 2018
Ketamine for social anxiety disorder: a randomized, placebo-controlled crossover trial
Taylor JH, Landeros-Weisenberger A, Coughlin C, et al.
Design: Randomized placebo-controlled crossover
Key finding: Ketamine significantly reduced social anxiety symptoms compared with placebo.
View on PubMedJournal of Psychopharmacology · 2017
Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders
Glue P, Medlicott NJ, Harland S, et al.
Design: Ascending-dose controlled study
Key finding: Dose-related reductions in anxiety within one hour, lasting up to a week in some patients.
View on PubMedOCD
Early research shows rapid reductions in obsessive symptoms after a single infusion. Durability of benefit and optimal dosing are still being studied.
Neuropsychopharmacology · 2013
Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept
Rodriguez CI, Kegeles LS, Levinson A, et al.
Design: Randomized placebo-controlled crossover
Key finding: 50% of participants met response criteria one week after ketamine vs 0% after placebo.
View on PubMedBipolar Depression
Studies in people with bipolar depression already on mood stabilizers show rapid antidepressant effects, with close monitoring for mood switching.
Archives of General Psychiatry · 2010
A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression
Diazgranados N, Ibrahim L, Brutsche NE, et al.
Design: Randomized placebo-controlled crossover
Key finding: Significant improvement within 40 minutes, lasting about three days, in patients maintained on lithium or valproate.
View on PubMedChronic Pain & CRPS
Ketamine has decades of use in anesthesia. Trials in complex regional pain syndrome (CRPS) and meta-analyses of chronic pain show meaningful short-term relief, with longer-term data still limited.
Pain · 2009
Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study
Schwartzman RJ, Alexander GM, Grothusen JR, et al.
Design: Double-blind placebo-controlled trial
Key finding: Ketamine infusions reduced pain in CRPS patients over a 12-week follow-up.
View on PubMedPain · 2009
Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1
Sigtermans MJ, van Hilten JJ, Bauer MCR, et al.
Design: Randomized double-blind placebo-controlled trial
Key finding: A 4.2-day infusion significantly reduced pain scores for up to 11 weeks.
View on PubMedAnesthesia & Analgesia · 2019
Ketamine infusions for chronic pain: a systematic review and meta-analysis of randomized controlled trials
Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP
Design: Meta-analysis of RCTs
Key finding: Ketamine infusions provided significant short-term pain relief, with stronger effects at higher doses.
View on PubMedAlcohol & Substance Use
Ketamine combined with therapy is being studied to support recovery. Early trials report improved abstinence, but this remains an investigational use.
American Journal of Psychiatry · 2022
Ketamine for reduction of alcohol use disorder: a randomised, placebo-controlled, phase 2 trial
Grabski M, McAndrew A, Lawn W, et al.
Design: Phase 2 RCT (KARE), n=96
Key finding: Ketamine plus psychological therapy increased days abstinent at six-month follow-up compared with placebo.
View on PubMedAmerican Journal of Psychiatry · 2020
A single ketamine infusion combined with motivational enhancement therapy for alcohol use disorder: a randomized midazolam-controlled pilot trial
Dakwar E, Levin F, Hart CL, et al.
Design: Randomized midazolam-controlled pilot
Key finding: Ketamine was associated with lower rates of heavy drinking and longer time to relapse.
View on PubMedSafety & Side Effects
At the low doses used for mental health, side effects are usually short-lived and resolve within hours: dissociation, raised blood pressure, nausea and dizziness. Treatment should take place in a monitored clinical setting.
Lancet Psychiatry · 2018
Side-effects associated with ketamine use in depression: a systematic review
Short B, Fong J, Galvez V, Shelker W, Loo CK
Design: Systematic review, 60 studies
Key finding: Acute side effects were common but transient; long-term safety of repeated dosing needs more study.
View on PubMedJAMA Psychiatry · 2017
A consensus statement on the use of ketamine in the treatment of mood disorders
Sanacora G, Frye MA, McDonald W, et al.
Design: American Psychiatric Association task force consensus
Key finding: Recommends patient screening, medical monitoring and clinician training for safe ketamine use.
View on PubMed