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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 17 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 evidence on esketamine for anxiety is mixed and mostly indirect. In treatment-resistant depression, esketamine appears to reduce anxiety symptoms alongside depression, with one systematic review concluding it lowers anxiety in both anxiety disorders and treatment-resistant depression, though the evidence is preliminary and anxiety may return after maintenance treatment stops. In surgical settings results diverge: several small trials report lower postoperative anxiety scores, but the largest and most rigorous of these found no reduction in postoperative anxiety at days 3 or 30. Most data come from small samples, short follow-up, and populations with comorbid depression or surgery rather than primary anxiety disorders.

Evidence by study

Direction is which way each study's own result points, not our rating of the study. All 25 matching studies were reviewed; the 17 that directly address the question are shown here.

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
Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review. 2026 systematic review 78 Supports Across 78 heterogeneous studies, es/ketamine was 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 soon after maintenance ends; no esketamine study was found for primary anxiety disorders.
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 nasal spray produced a greater anxiolytic effect on the Hamilton Anxiety scale in bipolar than in unipolar treatment-resistant depression, alongside reduced depressive symptoms.
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 retrospective observational study 30 Supports Esketamine nasal spray was associated with a 53.3% response rate and 33.33% remission rate at 3 months, with anxiety assessed by the Hamilton Anxiety Rating Scale; common adverse effects were dizziness, dissociation, sedation, and hypertension.
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 (HAM-A) and impulsivity decreased during six months of intranasal esketamine treatment, with no difference in six-month remission by borderline personality disorder status.
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 pooled analysis of two phase 3 RCTs 518 Mixed Esketamine plus a new oral antidepressant increased odds of response and remission versus antidepressant plus placebo, but within the esketamine group response and remission were 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 phase 3 randomized double-blind trial (secondary analysis) 223 Supports At day 28, fewer patients on esketamine plus antidepressant reported impairment on the anxiety/depression dimension of the EQ-5D-5L than those on placebo plus antidepressant (69.2% vs 78.0%), alongside greater gains in quality of life and functioning.
The effect of esketamine on postoperative anxiety and depression in patients with thyroid cancer: A randomized, double-blind, placebo-controlled, parallel-group trial. 2025 RCT 80 Supports A single intravenous dose of esketamine (0.5 mg/kg) at anesthesia induction significantly reduced postoperative anxiety and depression scores compared with saline.
Effect of esketamine on postoperative depression and anxiety in patients undergoing cardiac valve surgery: a randomised, placebo-controlled, double-blinded clinical trial. 2025 RCT 142 Supports A single 0.3 mg/kg dose of esketamine at anesthesia induction lowered rates of anxiety at postoperative day 7 (11.3% vs 35.2%) and depression compared with placebo, with reduced delirium and no difference in adverse events.
Esketamine for Postoperative Anxiety After Major Abdominal Tumor Surgery: A Randomized Clinical Trial 2026 RCT 180 No effect Esketamine did not reduce postoperative anxiety: response rates on day 3 were 39.5% with esketamine versus 42.5% with placebo, and Hamilton Anxiety scores were similar 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 60 Supports Combined perioperative esketamine exposure was associated with lower postoperative anxiety and depression scores at days 3 and 7, with no difference in pain scores or adverse events; the authors call for prospective RCTs to confirm.
Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial. 2026 RCT 77 Supports Perioperative sub-anesthetic esketamine reduced the incidence of anxiety on postoperative days 1 and 3 and of depression and sleep disturbance, without affecting early immune function or analgesia.
Effects of Esketamine on Postoperative Delirium and Postoperative Cognitive Function in Elderly Gastrointestinal Tumor Patients with Preoperative Anxiety 2025 RCT Supports Low-dose intravenous esketamine (0.25 mg/kg) during anesthesia induction decreased postoperative delirium incidence and improved early postoperative cognitive function in elderly patients with preoperative anxiety.
Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review. 2025 systematic review 16 Supports Across 16 studies (mostly case studies and observational), ketamine or esketamine was associated with immediate improvements in depression, anxiety, and suicidality that were maintained for weeks to months, and was generally well tolerated.
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 linked ketamine's psychoactive effects to better therapeutic outcomes while 13 of 29 found no linkage, and the single social anxiety disorder study found no relationship; the overall relationship remains indeterminate.
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 and pain in mice, apparently via inhibition of hippocampal RIPK1/RIPK3/MLKL-mediated necroptosis.
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 pain-related anxiety-like behaviors in mice, associated with mGluR5 downregulation and BDNF/TrkB activation in the prelimbic cortex.
N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. 2026 animal study Mixed DMT, but not S-ketamine, reversed stress-induced hypolocomotion and increased open-arm exploration in anxiety tests, while neither compound altered novelty-suppressed feeding behavior.

Points of agreement

  • In treatment-resistant depression, esketamine reduces anxiety symptoms alongside depressive symptoms across observational cohorts and trial secondary analyses.
  • The systematic review of anxiety outcomes concludes es/ketamine is associated with reduced anxiety in both anxiety disorders and treatment-resistant depression, with benefit sustained under repeated or maintenance dosing.
  • Several perioperative RCTs and cohorts report lower postoperative anxiety scores after esketamine.
  • Anxiety reduction appears to track depression improvement, and baseline anxiety may moderate who responds best.

Conflicts

  • The largest perioperative RCT found no effect of esketamine on postoperative anxiety at days 3 or 30, contradicting smaller trials and cohorts reporting anxiety reductions.
  • One pooled trial analysis found patients without significant baseline anxiety were more likely to respond, suggesting anxiety may predict poorer response, while other work reports anxiolytic benefit.
  • In animal work, S-ketamine failed to reverse some anxiety-like behaviors that DMT reversed, indicating the anxiolytic signal is not uniform even preclinically.

Gaps

  • Almost no esketamine studies in primary DSM-5 anxiety disorders; the systematic review found only ketamine studies for that indication.
  • Durability is unclear: anxiety may re-emerge soon after maintenance treatment ends, and most trials follow patients only days to months.
  • Most clinical data come from small samples, retrospective or post-hoc designs, and populations with comorbid depression or surgery rather than anxiety disorders.
  • Dose, route, and dosing schedule vary widely across studies, and no dose-response for anxiety outcomes is established.
  • Blinding integrity and expectancy effects are rarely addressed, and older adults, youth, and long-term maintenance populations are understudied.
Browse these studies in the library

Common questions

What does the research agree on about esketamine for anxiety?
  • In treatment-resistant depression, esketamine reduces anxiety symptoms alongside depressive symptoms across observational cohorts and trial secondary analyses.
  • The systematic review of anxiety outcomes concludes es/ketamine is associated with reduced anxiety in both anxiety disorders and treatment-resistant depression, with benefit sustained under repeated or maintenance dosing.
  • Several perioperative RCTs and cohorts report lower postoperative anxiety scores after esketamine.
  • Anxiety reduction appears to track depression improvement, and baseline anxiety may moderate who responds best.
Where do studies on esketamine for anxiety conflict?
  • The largest perioperative RCT found no effect of esketamine on postoperative anxiety at days 3 or 30, contradicting smaller trials and cohorts reporting anxiety reductions.
  • One pooled trial analysis found patients without significant baseline anxiety were more likely to respond, suggesting anxiety may predict poorer response, while other work reports anxiolytic benefit.
  • In animal work, S-ketamine failed to reverse some anxiety-like behaviors that DMT reversed, indicating the anxiolytic signal is not uniform even preclinically.
What is still unknown about esketamine for anxiety?
  • Almost no esketamine studies in primary DSM-5 anxiety disorders; the systematic review found only ketamine studies for that indication.
  • Durability is unclear: anxiety may re-emerge soon after maintenance treatment ends, and most trials follow patients only days to months.
  • Most clinical data come from small samples, retrospective or post-hoc designs, and populations with comorbid depression or surgery rather than anxiety disorders.
  • Dose, route, and dosing schedule vary widely across studies, and no dose-response for anxiety outcomes is established.
  • Blinding integrity and expectancy effects are rarely addressed, and older adults, youth, and long-term maintenance populations are understudied.
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

39 articles · 24 from the last two years · 3,769 participants across 25 studies reporting sample size

Common study designs

animal study 3 systematic review 4 observational cohort 2 randomized controlled trial 12 secondary analysis of a longitudinal cohort 1

Research volume by year

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39 studies whose primary subject is esketamine for anxiety since 2020

Studies about esketamine for anxiety per year, 2020 to 2026, peaking at 17 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 17 in 2026
Year Studies
2020 2
2021 2
2022 1
2023 8
2024 2
2025 7
2026 17

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

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

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

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 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

Clinical trials

All esketamine for anxiety trials →