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Ketamine for anxiety

Studies whose primary subject is both Ketamine and Anxiety, with an evidence synthesis read across the most-cited and most recent of them.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Ketamine, racemic ketamine, arketamine, R-ketamine, Anxiety, generalized anxiety disorder, then ranked by relevance.

The direct evidence on ketamine for anxiety is thin but mostly encouraging: a small double-blind, midazolam-controlled dose-escalation study in treatment-resistant generalized and social anxiety disorder found anxiety improvements within an hour that lasted up to a week, with a dose-response pattern. In depressed populations, post hoc analyses suggest anxious depression responds at least as well as, or better than, non-anxious depression to a single infusion, and a very large retrospective series of low-dose buccal ketamine reported large drops in anxiety scores. However, a 180-patient placebo-controlled trial of perioperative esketamine found no reduction in postoperative anxiety, so benefits may be context- and population-specific, and samples in the anxiety-specific trials are very small.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Study Design Sample size Direction Finding
Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study 2020 double-blind, psychoactive-controlled ascending dose study 12 Supports Anxiety ratings improved within an hour of ketamine dosing and persisted up to one week, with a dose-response profile for anxiolytic effects, while midazolam had only minor brief effects.
Effect of Baseline Anxious Depression on Initial and Sustained Antidepressant Response to Ketamine 2014 post hoc analysis of a single-arm open-label trial 26 Supports Patients with anxious depression had significantly fewer depressive symptoms than those with nonanxious depression across multiple follow-up days after a single ketamine infusion.
A single infusion of ketamine improves depression scores in patients with anxious bipolar depression 2014 post-hoc analysis of a clinical trial 36 Supports Both anxious and non-anxious patients with bipolar depression showed significant antidepressant responses to a single ketamine infusion, with no significant drug-by-anxiety interaction.
784. A Retrospective Report of Efficacy and Tolerability of Low Daily Dose Ketamine for Depression and Anxiety in a Large Population Sample 2026 retrospective observational study 59759 Supports Four weeks of low daily-dose buccal ketamine was associated with a fall in GAD-7 anxiety scores from 15.5 to 7.7, with a 63.4% response rate and 31.7% remission rate, alongside about 31% dropout.
Esketamine for Postoperative Anxiety After Major Abdominal Tumor Surgery: A Randomized Clinical Trial 2026 randomized controlled trial 180 No effect Esketamine did not reduce postoperative anxiety: response rates on postoperative day 3 were 39.5% versus 42.5% with placebo, and anxiety scores were similar at days 3 and 30.
Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial. 2026 randomized controlled trial 77 Supports Perioperative sub-anesthetic esketamine significantly reduced the incidence of postoperative anxiety on days 1 and 3 compared with placebo.
Perioperative esketamine exposure and postoperative depression and anxiety in elderly patients undergoing joint replacement surgery: a retrospective cohort study 2026 retrospective cohort study 60 Supports Combined perioperative esketamine exposure was associated with significantly lower anxiety and depression scores at postoperative days 3 and 7.
Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder 2010 open-label trial 33 Supports A single ketamine infusion significantly improved depression, anxiety, and hopelessness at all post-infusion time points, alongside rapid reductions in suicidal ideation.
Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial 2015 randomized controlled trial 24 Mixed Ketamine did not differ from midazolam on the primary suicidal ideation outcome at 24 hours but showed a significant difference at 48 hours, and the treatment effect was no longer significant by the end of the 7-day assessment.
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence 2007 randomized controlled trial 59 No effect Repeated versus single ketamine-assisted psychotherapy sessions did not differ on anxiety, depression, or craving, though the multiple-session group had higher one-year abstinence.
Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study 2026 case study 1 Supports Greater therapeutic gains followed ketamine-assisted psychotherapy sessions with higher mystical-experience scores, and the patient attributed improvement to the psychological and spiritual impact of the sessions.
Ketamine effects on EEG and their links to therapy differ across treatment-resistant major depression, post-traumatic stress disorder, and obsessive-compulsive disorder 2026 experimental, within-subjects, counterbalanced, placebo-controlled 42 Mixed Ketamine's EEG effects and their correlation with symptom-scale change varied by frequency band, electrode, and diagnosis, with dose-dependent alpha changes in PTSD but not MDD.
Esketamine alleviates trigeminal neuralgia and anxiety-like behaviors in mice by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis. 2026 animal study Supports Esketamine dose-dependently alleviated anxiety-like and despair-like behaviors and pain in mice, effects reversed by a necroptosis activator.
Ketamine Metabolites Promote Anxiolysis and Hydrocortisone Stress Buffering in Zebrafish. 2026 experimental study Mixed The hydroxynorketamine isomer RANK produced anxiolytic-like effects at baseline and under stress, whereas SHANK increased anxiety-like behavior at baseline but both isomers attenuated hydrocortisone-induced hyperarousal.
A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders 2017 review and consensus statement Supports Ketamine can produce rapid and robust antidepressant effects in treatment-resistant mood and anxiety disorders, but the authors emphasize small samples, limited long-term efficacy and safety data, and off-label risk.
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L’humeur Et De L’anxiété (Canmat) Concernant L’utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur 2020 systematic review Supports Single-dose intravenous racemic ketamine has Level 1 evidence for efficacy in treatment-resistant depression and is recommended as a third-line treatment, with weaker evidence for repeated or non-IV use.
Oral ketamine for the treatment of pain and treatment-resistant depression 2016 systematic review Unclear The methodological strength of studies on ketamine's antidepressant effects was low regardless of administration route, and longer-term consequences of oral ketamine remain understudied.
Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions 2013 review Supports A single subanesthetic intravenous dose of ketamine exerts rapid antidepressant effects and reduces suicidal ideation, but optimal dose, route, maintenance strategy, and response biomarkers remain unknown.
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS 2016 review Supports A single subanesthetic ketamine dose produces rapid antidepressant effects in treatment-resistant depression, likely via a glutamate surge leading to synaptogenesis in the prefrontal cortex.
Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors 2018 review Supports Preclinical and clinical evidence supports rapid antidepressant and anti-suicidal effects of ketamine, with action linked to mTOR signaling.
Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder 2018 narrative review Supports Multiple baseline predictors of ketamine response were identified, with high BMI and family history of alcohol use disorder the most replicated, though a complete response phenotype remains incomplete.
Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to anN-Methyl-D-Aspartate Antagonist 2009 open-label trial 23 Supports MADRS scores improved significantly after ketamine, but BDNF levels did not change and were not associated with antidepressant response.
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression 2020 preclinical study Mixed Psilocybin and LSD produced persistent antidepressant-like effects in a rat model, whereas ketamine produced only a transient effect.
Psychedelic Therapies in the Management of Post-Traumatic Stress Disorder 2026 review Supports Ketamine offers rapid symptom alleviation in PTSD, notably for treatment-resistant cases with high self-harm and suicide risk, while MDMA-assisted therapy showed high efficacy.
Is the reduction in suicidal ideation and deliberate self-harm during intranasal esketamine treatment independent of antidepressant response? A secondary, longitudinal analysis of a real-world TRD cohort with and without comorbid borderline personality disorder 2026 secondary analysis of a longitudinal cohort Supports The within-person reduction in suicidal ideation over six months remained significant after adjusting for time-varying depressive severity, suggesting an anti-suicidal effect partly independent of mood improvement.

Points of agreement

  • Multiple lines of evidence, including a small controlled trial in anxiety disorders, report rapid anxiolytic effects of ketamine within hours that can persist for days to about a week.
  • Anxious depression does not appear to be a poor-response subtype for ketamine; post hoc analyses in unipolar and bipolar depression found anxious patients responded at least as well as non-anxious patients.
  • Reviews and consensus statements consistently describe rapid antidepressant and anti-suicidal effects while flagging small samples and limited long-term safety and efficacy data.
  • Several perioperative trials and cohort studies report reduced postoperative anxiety or depression scores with esketamine.

Conflicts

  • A large placebo-controlled trial in surgical patients found no effect of esketamine on postoperative anxiety, while smaller perioperative trials and a retrospective cohort reported reductions.
  • The anxiety-disorder trial found anxiolytic effects of ketamine beyond a midazolam control, whereas the suicidal-ideation trial found no 24-hour difference from midazolam on its primary outcome.
  • Rodent work suggests ketamine's antidepressant-like effect is transient compared with classic psychedelics, contrasting with clinical reports of effects lasting up to a week or longer.

Gaps

  • Very few studies enroll patients whose primary diagnosis is an anxiety disorder; most anxiety findings come from depressed or surgical populations.
  • Anxiety-specific samples are very small (e.g., 12 patients), and the largest anxiety dataset is retrospective and uncontrolled.
  • Durability beyond about one week, and effects of maintenance dosing, are largely unstudied for anxiety.
  • Optimal dose, route, and dosing schedule for anxiety are unresolved, and blinding is difficult given ketamine's dissociative effects.
  • Long-term safety, tolerability, and abuse liability in anxiety populations are not well characterized.
Browse these studies in the library

Common questions

What does the research agree on about ketamine for anxiety?
  • Multiple lines of evidence, including a small controlled trial in anxiety disorders, report rapid anxiolytic effects of ketamine within hours that can persist for days to about a week.
  • Anxious depression does not appear to be a poor-response subtype for ketamine; post hoc analyses in unipolar and bipolar depression found anxious patients responded at least as well as non-anxious patients.
  • Reviews and consensus statements consistently describe rapid antidepressant and anti-suicidal effects while flagging small samples and limited long-term safety and efficacy data.
  • Several perioperative trials and cohort studies report reduced postoperative anxiety or depression scores with esketamine.
Where do studies on ketamine for anxiety conflict?
  • A large placebo-controlled trial in surgical patients found no effect of esketamine on postoperative anxiety, while smaller perioperative trials and a retrospective cohort reported reductions.
  • The anxiety-disorder trial found anxiolytic effects of ketamine beyond a midazolam control, whereas the suicidal-ideation trial found no 24-hour difference from midazolam on its primary outcome.
  • Rodent work suggests ketamine's antidepressant-like effect is transient compared with classic psychedelics, contrasting with clinical reports of effects lasting up to a week or longer.
What is still unknown about ketamine for anxiety?
  • Very few studies enroll patients whose primary diagnosis is an anxiety disorder; most anxiety findings come from depressed or surgical populations.
  • Anxiety-specific samples are very small (e.g., 12 patients), and the largest anxiety dataset is retrospective and uncontrolled.
  • Durability beyond about one week, and effects of maintenance dosing, are largely unstudied for anxiety.
  • Optimal dose, route, and dosing schedule for anxiety are unresolved, and blinding is difficult given ketamine's dissociative effects.
  • Long-term safety, tolerability, and abuse liability in anxiety populations are not well characterized.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Ketamine for anxiety, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Ketamine for anxiety or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

The full method, including what a person does and does not review, is on the methods page.

Ask your own question in the Research Synthesis Tool

198 articles · 75 from the last two years · 85,841 participants across 113 studies reporting sample size

Common study designs

review 26 systematic review 13 experimental study 13 observational cohort 10 randomized controlled trial 24

Research volume by year

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196 studies whose primary subject is ketamine for anxiety since 2007

Studies about ketamine for anxiety per year, 2007 to 2026, peaking at 39 in 2026 Bar chart: one bar per year, taller where more studies were published that year. 0 20 40 2010 2015 2020 2025
2026 is partial
Show the numbers
Studies about ketamine for anxiety per year, 2007 to 2026, peaking at 39 in 2026
Year Studies
2007 2
2008 0
2009 1
2010 2
2011 0
2012 0
2013 1
2014 4
2015 4
2016 3
2017 7
2018 8
2019 2
2020 17
2021 15
2022 20
2023 18
2024 21
2025 32
2026 39

Research

Synthesize the evidence →

Insomnia and anxiety exhibit distinct short-term associations following ketamine in treatment-resistant depression

Translational Psychiatry October 6, 2026 Nadia S. Hejazi, Mina Kheirkhah, Robin Chholak et al.

Insomnia and anxiety frequently co-occur with treatment-resistant depression (TRD). This study examined short-term changes in depression, anxiety, and insomnia symptoms post-ketamine in TRD and their inter-relationships. Seventy-one patients with TRD were assessed at baseline and 24 h after intravenous ketamine (0.5 mg/kg). Depression, anxiety, and insomnia were measured using the...

DOI: 10.1038/s41398-026-04443-2 (opens in new tab) Full text (opens in new tab)

Esketamine for Postoperative Anxiety After Major Abdominal Tumor Surgery: A Randomized Clinical Trial

Drug Design, Development and Therapy September 1, 2026 Xiaoying Cui, Wutao Chen, Jinyu Wang et al.

Purpose: Postoperative anxiety is common in surgical patients and may impair recovery, especially in the patients with preoperative anxiety. However, effective strategies for treating postoperative anxiety remain limited. We hypothesized that esketamine could reduce postoperative anxiety in patients with preoperative anxiety undergoing major abdominal tumor surgery. Patients and Methods: 180...

DOI: 10.2147/dddt.s632479 (opens in new tab)

784. A Retrospective Report of Efficacy and Tolerability of Low Daily Dose Ketamine for Depression and Anxiety in a Large Population Sample

The International Journal of Neuropsychopharmacology September 1, 2026 A Nunes, J E Cunningham, B Leden et al.

Abstract Background Use of intravenous ketamine or intranasal esketamine for depression is frequently limited due to resource requirements and cost. Alternative treatment models have used oral, sublingual or intranasal racemic ketamine, but optimal doses and frequency of administration remain unclear. Dosing modelled from the standard 0.5-1.0mg/kg twice weekly IV ketamine result in transient...

DOI: 10.1093/ijnp/pyag040.129 (opens in new tab) Full text (opens in new tab)

Perioperative esketamine exposure and postoperative depression and anxiety in elderly patients undergoing joint replacement surgery: a retrospective cohort study

BMC Anesthesiology August 26, 2026 Mao Li, Wen Wen, Xiang Wen

Postoperative depression and anxiety are common in elderly patients undergoing joint replacement surgery and may affect recovery. Esketamine has rapid antidepressant effects, but evidence for combined perioperative use remains limited, particularly in elderly patients undergoing joint replacement surgery. This study evaluated the association between combined perioperative esketamine exposure...

DOI: 10.1186/s12871-026-04199-8 (opens in new tab)

Esketamine alleviates trigeminal neuralgia and anxiety-like behaviors in mice by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.

Brain Research Bulletin August 1, 2026 Rui Dong, Jiaxin Liu, Yumei Shen et al.

Trigeminal neuralgia (TN) is a debilitating orofacial pain condition frequently complicated by anxiety and depression, forming a self-reinforcing pain-affect cycle with limited therapeutic options. A TN mouse model with anxiety-like behavior was established using partial infraorbital nerve transection (pIONT). Esketamine (ES) (5 or 10 mg/kg) was administered intraperitoneally from postoperative...

DOI: 10.1016/j.brainresbull.2026.111987 (opens in new tab) Full text (opens in new tab) Esketamine Hippocampus Pain-affect comorbidity Ripk1/ripk3/mlkl +1

Effect of Esketamine Pretreatment on Necroptosis in Mice with Trigeminal Neuralgia and Anxiety-Like Behavior via the RIP1/RIP3/MLKL Pathway.

Cellular and molecular neurobiology July 28, 2026 Rui Dong, Yuan Tian, Chendi Zhao et al.

To explore the effect of esketamine (ES) pretreatment on necroptosis in mice with trigeminal neuralgia accompanied by anxiety-like behavior and its correlation with the RIP1/RIP3/MLKL signaling pathway. Thirty male C57BL/6J mice were randomized into five groups (n=6): Control, Sham, model group (PIONT), PIONT+NS, and PIONT+ES. Trigeminal neuralgia model was established by left infraorbital...

DOI: 10.1007/s10571-026-01782-y (opens in new tab) Full text (opens in new tab) Anxiety-like behavior Esketamine pretreatment Necroptosis Rip1/rip3/mlkl pathway +1

Psychedelic Therapies in the Management of Post-Traumatic Stress Disorder

Journal of Education, Health and Sport July 16, 2026 Jakub Bajer, Aleksandra Włodarczyk, Hubert Kulawinek et al.

Background. Post-Traumatic Stress Disorder (PTSD) is an important public health challenge typically treated with trauma-focused psychotherapy and Selective Serotonin Reuptake Inhibitors (SSRIs). However, high rates of residual symptoms associated with these standard treatments have led to a renewed interest in psychedelic-assisted therapies. Aim. This review attempts to examine emerging...

DOI: 10.12775/jehs.2026.94.73071 (opens in new tab) Traumatic stress Ketamine Psilocybin Anxiety disorder +5

Is the reduction in suicidal ideation and deliberate self-harm during intranasal esketamine treatment independent of antidepressant response? A secondary, longitudinal analysis of a real-world TRD cohort with and without comorbid borderline personality disorder

Open Mind July 13, 2026 Vassilis Martiadis, Fabiola Raffone preprint

In acute trials of intravenous and intranasal ketamine/esketamine, the rapid anti-suicidal effect appears to be at least partly independent of the overall antidepressant response. That question has, to our knowledge, never been examined in a real-world esketamine cohort followed for six months, nor in a sample enriched for comorbid borderline personality disorder (BPD), a population excluded...

DOI: 10.17605/osf.io/xk28a (opens in new tab) Major depressive disorder Anxiety Suicidal ideation Impulsivity +11

Ketamine Metabolites Promote Anxiolysis and Hydrocortisone Stress Buffering in Zebrafish.

Behavioural Brain Research July 9, 2026 Jeffrey R Kelly, Lindsey S Brasfield, Aryssa H Kelsey et al.

Anxiety and stress-related disorders affect over 280 million individuals worldwide and remain inadequately treated by current pharmacotherapies, which are often limited in efficacy and tolerability. Ketamine produces rapid therapeutic effects in mood and anxiety disorders, but its clinical use is constrained by dissociative side effects and abuse liability. Ketamine metabolites, particularly (2...

DOI: 10.1016/j.bbr.2026.116230 (opens in new tab) Full text (opens in new tab) Anxiety Hydroxynorketamine Stress Zebrafish

Ketamine effects on EEG and their links to therapy differ across treatment-resistant major depression, post-traumatic stress disorder, and obsessive-compulsive disorder

The International Journal of Neuropsychopharmacology July 6, 2026 Shabah M. Shadli, Neda Nasrollahi, Calvin K. Young et al.

BACKGROUND: Neurotic disorders - major depressive disorder (MDD), panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and specific phobia - have differing pharmaceutical profiles. But all, even when resistant to conventional treatment (TR), respond quickly to low dose (0.5-1.0 mg/kg I.M.) ketamine....

DOI: 10.1093/ijnp/pyag037 (opens in new tab) Full text (opens in new tab) Panic disorder Ketamine Anxiety disorder Major depressive disorder +11

Clinical trials

All ketamine for anxiety trials →