Skip to content

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 research suggests ketamine and esketamine can reduce anxiety symptoms, with effects appearing within hours and lasting up to about a week in some studies, though evidence quality is generally low and sample sizes are often small. A large retrospective study of low-dose buccal ketamine found anxiety scores dropped substantially over four weeks, but about a third of participants dropped out. Results are mixed: some controlled trials in surgical and treatment-resistant anxiety populations found no benefit over placebo, and durability beyond a few weeks is largely unstudied.

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
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 available data have significant limitations including small samples and lack of long-term efficacy and safety data.
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 Depression, anxiety, and hopelessness were significantly improved at all time points after a single ketamine infusion.
Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial 2015 randomized controlled trial 24 Mixed Ketamine did not significantly reduce suicidal ideation versus midazolam at 24 hours on the primary outcome, but a significant difference emerged at 48 hours and the treatment effect was no longer significant by day 7.
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression 2020 preclinical study Opposes In a rat depression model, ketamine produced only a transient antidepressant-like effect, whereas psilocybin and LSD produced persistent effects.
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS 2016 review Supports A single subanesthetic dose of ketamine produces rapid antidepressant effects in treatment-resistant depression, likely via a glutamate surge leading to synaptogenesis.
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence 2007 randomized controlled trial 59 No effect No differences between single and multiple ketamine-assisted psychotherapy sessions were found in depression, anxiety, craving for heroin, or understanding of the meaning of life.
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 ketamine's rapid antidepressant and anti-suicidal action, linked to the mTOR signaling pathway.
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 the improvement was not mediated by changes in BDNF levels.
Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder 2018 narrative review Supports Multiple pretreatment predictors of ketamine response were identified, with high BMI and positive family history of alcohol use disorder being the most replicated.
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 and later relapse after ketamine infusion compared to those with nonanxious depression.
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 adults with treatment-resistant depression and is recommended as a third-line treatment, though evidence for multiple infusions is limited to Level 3.
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 had significant antidepressant responses to ketamine, with no clear disadvantage for the anxious group.
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 Ketamine produced rapid and sustained anxiolytic effects with a dose-response profile, with improvements in anxiety ratings within an hour and persisting up to one week.
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 is low regardless of route, and oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability, but longer-term consequences remain understudied.
Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions 2013 review Supports A single intravenous subanesthetic dose of ketamine exerts rapid antidepressant effects and reduces suicidal ideation, but optimal dosing, administration modality, and biomarkers remain unknown.
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 reductions in anxiety scores (GAD-7 from 15.5 to 7.7), with a response rate of 63.4% and remission rate of 31.7%, though about 31% of participants dropped out by week 4.
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 compared to placebo: response rates on postoperative day 3 were 39.5% with esketamine versus 42.5% with placebo, and anxiety scores were similar at days 3 and 30.
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 lower postoperative anxiety scores at days 3 and 7, alongside transiently lower IL-6 and TNF-alpha and higher BDNF.
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 behaviors in a mouse model of trigeminal neuralgia by inhibiting hippocampal necroptosis via the RIPK1/RIPK3/MLKL pathway.
Psychedelic Therapies in the Management of Post-Traumatic Stress Disorder 2026 review Supports Ketamine offers rapid symptom alleviation in PTSD, making it notably beneficial for treatment-resistant cases with high risk of self-harm and suicide.
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 statistically significant after adjusting for time-varying depressive severity, indicating an anti-suicidal effect partly independent of mood improvement.
Ketamine Metabolites Promote Anxiolysis and Hydrocortisone Stress Buffering in Zebrafish. 2026 experimental study Mixed Hydroxynorketamine isomers produced stereospecific behavioral effects: RANK was anxiolytic under baseline and stress conditions, while SHANK was anxiogenic at baseline but both isomers attenuated hydrocortisone-induced hyperarousal.
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 improvement differ by band, electrode, and diagnosis, with TR-PTSD showing dose-dependent alpha changes and TR-MDD showing none.
Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study 2026 case study 1 Supports Mystical-type experiences during ketamine-assisted psychotherapy appeared to play a meaningful role in therapeutic change for a patient with generalized anxiety disorder and migraines.
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 reduced the incidence of anxiety on postoperative days 1 and 3 compared with placebo, but did not significantly affect early immune function or acute postoperative analgesia.

Points of agreement

  • Multiple studies report rapid anxiolytic or antidepressant effects of ketamine and esketamine, with onset within hours and persistence up to about a week in some designs.
  • Anxious depression does not appear to reduce ketamine's antidepressant response; two post hoc analyses found anxious patients responded as well as or better than non-anxious patients.
  • Reviews consistently note that evidence quality is limited by small samples, short follow-up, and lack of long-term safety and efficacy data.
  • Ketamine's effects on mood and anxiety appear to involve glutamatergic and neuroplasticity mechanisms rather than BDNF changes alone.

Conflicts

  • A large retrospective study of low-dose buccal ketamine reported substantial anxiety reductions, while a randomized controlled trial of esketamine in surgical patients found no reduction in postoperative anxiety versus placebo.
  • Some controlled trials show anxiolytic benefit (treatment-resistant anxiety disorders, acoustic neuroma surgery), while others show no benefit over active placebo or placebo (suicidal ideation at 24 hours, postoperative anxiety).
  • Preclinical evidence suggests ketamine's antidepressant-like effects are transient compared with classic psychedelics, contrasting with clinical reports of sustained benefit.

Gaps

  • Durability of anxiolytic effects beyond one week to one month is largely unstudied.
  • Optimal dose, route, and dosing frequency for anxiety specifically remain unclear.
  • Most controlled trials have very small samples (12-36 patients), limiting generalizability.
  • Blinding is difficult due to ketamine's dissociative effects, and few studies use active placebos.
  • Long-term safety, abuse liability, and effects of repeated maintenance dosing are understudied.
  • Populations studied are heterogeneous (treatment-resistant depression, surgical patients, anxiety disorders, PTSD), making it hard to isolate anxiety-specific effects.
Browse these studies in the library

Common questions

What does the research agree on about ketamine for anxiety?
  • Multiple studies report rapid anxiolytic or antidepressant effects of ketamine and esketamine, with onset within hours and persistence up to about a week in some designs.
  • Anxious depression does not appear to reduce ketamine's antidepressant response; two post hoc analyses found anxious patients responded as well as or better than non-anxious patients.
  • Reviews consistently note that evidence quality is limited by small samples, short follow-up, and lack of long-term safety and efficacy data.
  • Ketamine's effects on mood and anxiety appear to involve glutamatergic and neuroplasticity mechanisms rather than BDNF changes alone.
Where do studies on ketamine for anxiety conflict?
  • A large retrospective study of low-dose buccal ketamine reported substantial anxiety reductions, while a randomized controlled trial of esketamine in surgical patients found no reduction in postoperative anxiety versus placebo.
  • Some controlled trials show anxiolytic benefit (treatment-resistant anxiety disorders, acoustic neuroma surgery), while others show no benefit over active placebo or placebo (suicidal ideation at 24 hours, postoperative anxiety).
  • Preclinical evidence suggests ketamine's antidepressant-like effects are transient compared with classic psychedelics, contrasting with clinical reports of sustained benefit.
What is still unknown about ketamine for anxiety?
  • Durability of anxiolytic effects beyond one week to one month is largely unstudied.
  • Optimal dose, route, and dosing frequency for anxiety specifically remain unclear.
  • Most controlled trials have very small samples (12-36 patients), limiting generalizability.
  • Blinding is difficult due to ketamine's dissociative effects, and few studies use active placebos.
  • Long-term safety, abuse liability, and effects of repeated maintenance dosing are understudied.
  • Populations studied are heterogeneous (treatment-resistant depression, surgical patients, anxiety disorders, PTSD), making it hard to isolate anxiety-specific effects.
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

185 articles · 77 from the last two years · 85,412 participants across 102 studies reporting sample size

Common study designs

review 27 systematic review 13 experimental study 14 observational cohort 9 randomized controlled trial 21

Research volume by year

Compare topics →

183 studies whose primary subject is ketamine for anxiety since 2007

Studies about ketamine for anxiety per year, 2007 to 2026, peaking at 37 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 37 in 2026
Year Studies
2007 2
2008 0
2009 1
2010 1
2011 0
2012 0
2013 1
2014 4
2015 3
2016 3
2017 3
2018 5
2019 1
2020 17
2021 14
2022 20
2023 17
2024 21
2025 33
2026 37

Research

Synthesize the evidence →

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

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

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

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

Annals of medicine July 3, 2026 Zheping Chen, Yaozhu Wang, Peilin Cong et al.

Patients undergoing acoustic neuroma (AN) surgery often experience postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were...

DOI: 10.1080/07853890.2026.2692804 (opens in new tab) Full text (opens in new tab) Esketamine Anxiety Depression Negative emotion +1

Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study

Journal of Psychoactive Drugs July 3, 2026 Miguel Joaquim Soares Teles Couceiro, Victor José da Conceição Teixeira Amorim Rodrigues, Nuno Manuel Correia Torres

This case study explores the potential role of mystical-type experiences in ketamine-assisted psychotherapy (KAP). A patient with generalized anxiety disorder and migraines underwent four intramuscular KAP sessions (0.5-0.9 mg/kg). Outcomes were assessed using the Outcome Questionnaire-45 (OQ-45), the Hood Mysticism Scale (HMS), and interviews. Greater therapeutic gains followed sessions with...

DOI: 10.1080/02791072.2026.2696253 (opens in new tab) Mysticism Anxiety disorder Therapeutic relationship Outcome game theory +4

Clinical trials

All ketamine for anxiety trials →