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Esketamine for anxiety

Studies whose primary subject is both Esketamine 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 Esketamine, S-ketamine, spravato, esketamine nasal spray, Anxiety, generalized anxiety disorder, then ranked by relevance.

The research suggests esketamine (and related ketamine) can reduce anxiety symptoms, but the evidence is strongest for anxiety occurring alongside depression or in the perioperative setting rather than for primary anxiety disorders. In treatment-resistant depression, several studies report reduced anxiety scores, and a systematic review concludes esketamine is associated with reduced anxiety in both anxiety disorders and treatment-resistant depression, though it calls the evidence preliminary. The main caveats are that most data come from small, short-term, often observational or post-hoc studies, and one well-powered randomized trial in surgical patients found no reduction in postoperative anxiety, so results are not fully consistent.

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
Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant 2020 randomized controlled trial Supports A significantly higher proportion of patients receiving esketamine plus an antidepressant reached meaningful improvement thresholds on depression scales by Day 28 compared with placebo plus antidepressant.
Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression 2023 observational cohort 70 Supports Esketamine reduced depressive symptoms at one and three months with no difference in response or remission between bipolar and unipolar groups, and showed a greater anxiolytic effect in bipolar than unipolar patients.
Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING) 2023 retrospective observational 149 Supports Machine learning classifiers predicted esketamine response with about 66-69% accuracy, and features such as anxious distress positively predicted response and remission.
Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study 2023 observational retrospective 26 Supports Esketamine reduced depression scores over three months and was well tolerated, with no reported abuse or misuse.
Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group 2023 post-hoc analysis of observational study 30 Supports Esketamine was associated with a 53.3% response rate and 33.3% remission rate at three months, with dizziness, dissociation, and sedation as common adverse effects.
Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response 2021 pooled post hoc analysis of randomized trials Supports Patients not responding within the first week of treatment still showed higher odds of response at day 28 with esketamine plus antidepressant than with antidepressant plus placebo.
Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review. 2025 systematic review Supports Initial evidence suggests ketamine is safe and may be effective for mood disorders, anxiety, and suicidality in youth, with improvements maintained for weeks to months.
Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray 2023 post hoc analysis of pooled randomized trials 518 Supports Esketamine plus a new oral antidepressant increased odds of response and remission versus antidepressant plus placebo, and response was more likely in patients without significant anxiety at baseline.
Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant 2023 randomized controlled trial 223 Supports At day 28, fewer patients on esketamine plus antidepressant reported impairment on the anxiety/depression dimension of a quality-of-life measure compared with placebo plus antidepressant.
The effect of esketamine on postoperative anxiety and depression in patients with thyroid cancer: A randomized, double-blind, placebo-controlled, parallel-group trial. 2025 randomized controlled trial 80 Supports A single intravenous dose of esketamine (0.5 mg/kg) during anesthesia induction significantly reduced postoperative anxiety and depression scores compared with placebo.
Preoperative Anxiety's Impact on the Median Effective Dose of Esketamine for Alleviating Propofol Injection Pain in Patients Undergoing Painless abortion: A Randomized, Double-Blind, Controlled Trial. 2024 randomized controlled trial 150 Supports Preoperative anxiety increased the esketamine dose needed to alleviate propofol injection pain, with anxious patients requiring 0.133 mg/kg versus 0.114 mg/kg for non-anxious patients.
Effect of esketamine on postoperative depression and anxiety in patients undergoing cardiac valve surgery: a randomised, placebo-controlled, double-blinded clinical trial. 2025 randomized controlled trial 142 Supports A single dose of esketamine (0.3 mg/kg) at anesthesia induction significantly reduced rates of depression and anxiety at postoperative day 7 compared with placebo.
Ketamine-induced altered states of consciousness: a systematic review of implications for therapeutic outcomes in psychiatric practices. 2024 systematic review 29 Mixed About half of the reviewed studies found a positive association between ketamine's psychoactive effects and therapeutic outcomes, while the rest found no or negative associations, leaving the relationship indeterminate.
Effects of Esketamine on Postoperative Delirium and Postoperative Cognitive Function in Elderly Gastrointestinal Tumor Patients with Preoperative Anxiety 2025 randomized controlled trial Supports Low-dose intravenous esketamine (0.25 mg/kg) during anesthesia induction decreased postoperative delirium incidence and improved early postoperative cognitive function.
Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study 2026 qualitative exploratory study 36 Supports Patients described four experiential domains of esketamine-induced dissociation, with psychic distance from suffering being most common, and most framed dissociation as neutral or subjectively meaningful rather than distressing.
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 with placebo, with similar response rates and anxiety scores at days 3 and 30, though depressive symptom scores were lower at day 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 Perioperative esketamine exposure was associated with lower postoperative depression and anxiety scores at days 3 and 7, with no difference in pain scores or adverse events.
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 pain and anxiety-like behaviors in a mouse model, apparently via inhibition of hippocampal necroptosis.
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 longitudinal cohort Supports The reduction in suicidal ideation over six months remained statistically significant after adjusting for depressive severity, suggesting an anti-suicidal effect partly independent of mood improvement.
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 postoperative depression, anxiety, and sleep disturbances compared with placebo, without significantly affecting immune function or analgesia.
N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. 2026 animal study Mixed DMT was as effective as S-ketamine in producing rapid antidepressant effects, but only DMT reversed stress-induced anxiety-like behaviors in the open field and elevated plus-maze tests.
Effects of Esketamine on EEG temporal dynamics in patients with depression 2026 observational study 5 Supports Subjective 'highness' increased up to 75 minutes after esketamine and 'happiness' improved up to 35 minutes, paralleled by a reduction in alpha power.
Intranasal esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A multicenter real-world longitudinal study. 2026 observational cohort 90 Supports Across the whole sample, anxiety and impulsivity decreased during six months of intranasal esketamine treatment, with no difference in remission by borderline personality disorder status.
Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review. 2026 systematic review Supports The authors conclude that esketamine/ketamine is associated with reduced anxiety in both anxiety disorders and treatment-resistant depression, with effects sustained especially with repeated or maintenance dosing, though anxiety may re-emerge after maintenance ends and the evidence is preliminary.
S-ketamine mitigates paclitaxel-induced pain-related anxiety-like behavior through downregulation of mGluR5 and activation of the BDNF/TrkB signaling pathway 2026 preclinical experimental study Supports S-ketamine alleviated paclitaxel-induced pain and anxiety-like behaviors in mice, associated with downregulation of mGluR5 and activation of BDNF/TrkB signaling.

Points of agreement

  • Multiple studies in treatment-resistant depression report reductions in anxiety symptoms alongside antidepressant effects.
  • Several perioperative randomized trials found reduced postoperative anxiety after a single esketamine dose.
  • A systematic review concludes esketamine/ketamine is associated with reduced anxiety in both anxiety disorders and treatment-resistant depression.
  • Animal studies consistently show anxiolytic-like effects of esketamine or S-ketamine.

Conflicts

  • One randomized trial in major abdominal tumor surgery found no reduction in postoperative anxiety with esketamine, while other perioperative trials reported significant anxiety reductions.
  • In one animal study, S-ketamine did not reverse stress-induced anxiety-like behavior whereas DMT did, contrasting with other preclinical findings of anxiolytic effects.
  • A systematic review of ketamine's psychoactive effects found the relationship to therapeutic outcomes indeterminate, with about half of studies showing no association.

Gaps

  • Most evidence comes from small, short-term, observational, or post-hoc studies rather than large dedicated anxiety trials.
  • Few studies focus on primary DSM-5 anxiety disorders; most assess anxiety as a secondary symptom in depression or surgical settings.
  • Durability of anxiolytic effects beyond a few months and after maintenance treatment ends is unclear.
  • Optimal dose, route, and dosing schedule for anxiety are not established.
  • Populations studied are narrow (mostly adults with treatment-resistant depression or surgical patients), with limited data in youth and the elderly.
  • Blinding integrity and placebo effects are rarely addressed.
Browse these studies in the library

Common questions

What does the research agree on about esketamine for anxiety?
  • Multiple studies in treatment-resistant depression report reductions in anxiety symptoms alongside antidepressant effects.
  • Several perioperative randomized trials found reduced postoperative anxiety after a single esketamine dose.
  • A systematic review concludes esketamine/ketamine is associated with reduced anxiety in both anxiety disorders and treatment-resistant depression.
  • Animal studies consistently show anxiolytic-like effects of esketamine or S-ketamine.
Where do studies on esketamine for anxiety conflict?
  • One randomized trial in major abdominal tumor surgery found no reduction in postoperative anxiety with esketamine, while other perioperative trials reported significant anxiety reductions.
  • In one animal study, S-ketamine did not reverse stress-induced anxiety-like behavior whereas DMT did, contrasting with other preclinical findings of anxiolytic effects.
  • A systematic review of ketamine's psychoactive effects found the relationship to therapeutic outcomes indeterminate, with about half of studies showing no association.
What is still unknown about esketamine for anxiety?
  • Most evidence comes from small, short-term, observational, or post-hoc studies rather than large dedicated anxiety trials.
  • Few studies focus on primary DSM-5 anxiety disorders; most assess anxiety as a secondary symptom in depression or surgical settings.
  • Durability of anxiolytic effects beyond a few months and after maintenance treatment ends is unclear.
  • Optimal dose, route, and dosing schedule for anxiety are not established.
  • Populations studied are narrow (mostly adults with treatment-resistant depression or surgical patients), with limited data in youth and the elderly.
  • Blinding integrity and placebo effects are rarely addressed.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Esketamine 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 Esketamine 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

38 articles · 25 from the last two years · 3,566 participants across 23 studies reporting sample size

Common study designs

animal study 3 systematic review 4 observational cohort 2 randomized controlled trial 10 secondary analysis of a longitudinal cohort 1

Research volume by year

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38 studies whose primary subject is esketamine for anxiety since 2020

Studies about esketamine for anxiety per year, 2020 to 2026, peaking at 16 in 2026 Bar chart: one bar per year, taller where more studies were published that year. 0 10 20 2020 2025
2026 is partial
Show the numbers
Studies about esketamine for anxiety per year, 2020 to 2026, peaking at 16 in 2026
Year Studies
2020 2
2021 2
2022 1
2023 7
2024 2
2025 8
2026 16

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)

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

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

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

N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine.

Neuropharmacology July 1, 2026 Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al. 1 citation

N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...

DOI: 10.1016/j.neuropharm.2026.110947 (opens in new tab) Full text (opens in new tab) Anxiety Depression Animal models Mouse +2

Effects of Esketamine on EEG temporal dynamics in patients with depression

UNC Libraries June 21, 2026 Verina Guirguis

Esketamine is an effective rapid-acting pharmacological intervention for treatment-resistant depression. However, the temporal dynamics of underlying brain networks associated with the improvement of depressive symptoms remain elusive. This observational study seeks to delineate alteration in network activity within 90 minutes of nasal Esketamine administration, with a focus on exploring its...

DOI: 10.17615/b350-9s23 (opens in new tab) Major depressive disorder Anxiety Treatment-resistant depression Depression economics +9

Intranasal esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A multicenter real-world longitudinal study.

Psychiatry Research June 16, 2026 Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi et al.

Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without...

DOI: 10.1016/j.psychres.2026.117288 (opens in new tab) Full text (opens in new tab) Anxiety Esketamine Treatment-resistant depression Borderline personality disorder +2

Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review.

Journal of psychopharmacology (Oxford, England) June 2026 Vasilios G Masdrakis, Zoe Tebbs, Vasilios Natsis et al.

Ketamine and esketamine ("es/ketamine") treatment protocols have been investigated in patients' samples with treatment-refractory anxiety disorders. We systematically reviewed publications in which es/ketamine was used to treat anxiety symptoms in the context of either Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) anxiety disorders or treatment-resistant...

DOI: 10.1177/02698811251389583 (opens in new tab) Full text (opens in new tab) Esketamine Anxiety disorders Anxious depression Treatment-refractory anxiety

S-ketamine mitigates paclitaxel-induced pain-related anxiety-like behavior through downregulation of mGluR5 and activation of the BDNF/TrkB signaling pathway

Frontiers in Neurology April 23, 2026 Jing Cao, ZiYuan Wang, GeGe Lv et al.

Background Paclitaxel (PTX), a broad-spectrum anti-tumor drug, is extensively employed as a first-line chemotherapy for solid tumors, including lung and breast cancers. However, it induces chemotherapy-related pain and anxiety in over 53% of patients. S-ketamine, the S-enantiomer of ketamine, exerts rapid antidepressant effects. In this study, we established a PTX model to examine the effects...

DOI: 10.3389/fneur.2026.1801549 (opens in new tab)

Clinical trials

All esketamine for anxiety trials →