Esketamine for Depressive Disorders

49 papers and 12 clinical trials exploring esketamine as a treatment for depressive disorders.

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Esketamine

Esketamine (Spravato) is the S-enantiomer of ketamine, approved as an intranasal treatment for treatment-resistant depression and MDD with acute suicidal ideation. It is administered under clinical supervision with post-dose monitoring and has reached over $1.6 billion in annual sales.

Full Esketamine profile

IndicationApproximately 260 million people worldwide are affected by depression.

Depressive Disorders

Depressive disorders, particularly major depressive disorder (MDD), are significant contributors to global mental health issues. Research into the therapeutic potential of psychedelics, such as psilocybin and ketamine, offers promising avenues for treatment, especially for cases that are resistant to conventional therapies.

Full Depressive Disorders profile

Academic Research

49 papers

Open Accessindividual

Long-term treatment with esketamine nasal spray in patients with treatment resistant depression: Results from the ESCAPE-LTE study

This Phase IV single-arm long-term extension trial (n=183) found that the vast majority of patients with treatment-resistant depression who achieved remission with esketamine nasal spray (plus an antidepressant) did not relapse over 136 weeks of treatment, with side effects largely resolving the same day and no new safety concerns identified.

Published: February 27, 2026
Journal: European Neuropsychopharmacology
Authors: Reif, A., Anıl, Y. A., Bitter, I., Buyze, J., Frey, R., DJ, F., Godinov, Y., Haggström, L., Kambarov, Y., Nielsen, R., Oliveira-Maia, A., von Holt, C., AH, Y., Cubała, W.

Open Accessindividual

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study

This double-blind Phase IIb trial (n=147) evaluated the efficacy, safety, and tolerability of esketamine nasal spray versus midazolam in reducing depressive (MDD) symptoms in adolescents at imminent risk for suicide (SI). The study finds that pooled doses of esketamine (56 and 84 mg) significantly reduce depressive symptoms at 24 hours, with common side effects including dizziness, nausea, and dissociation.

Published: January 1, 2026
Journal: Journal of the American Academy of Child & Adolescent Psychiatry
Authors: Bloch, M. H., Canuso, C. M., Chen, L. N., DelBello, M., Drevets, W. C., Fu, D. J., Kosik-Gonzalez, C., Lane, R., Moreno, C.

Open Accessindividual

Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial

In a phase 4, multicentre, double-blind randomised trial in adults with treatment‑resistant depression, intranasal esketamine monotherapy (56 mg and 84 mg) produced significant reductions in MADRS score versus placebo at day 28 (LS mean differences −5.1 and −6.8; effect sizes 0.48 and 0.63) and demonstrated rapid benefit at 24 hours. The tolerability profile was consistent with prior reports, most commonly nausea, dissociation, dizziness and headache.

Published: September 1, 2025
Journal: JAMA Psychiatry
Authors: Canuso, C. M., Drevets, W. C., Fu, D. J., Janik, A., Lane, R., Macaluso, M., Mattingly, G. W., Popova, V., Qiu, X., Shelton, R. C., Zajecka, J. M.

Paywallindividual

Efficacy and safety of esketamine for smoking cessation among patients diagnosed with lung cancer and major depression disorder: A randomized, placebo-controlled clinical trial

This multicenter, randomised, placebo-controlled clinical trial (n=236) investigates the efficacy and safety of esketamine (ESK) (8x35mg) for smoking cessation in patients with lung cancer and major depressive disorder (MDD). Eight weekly intranasal ESK sessions significantly improved both self-reported (44.1%) and biologically verified (28.8%) smoking abstinence at 6-month follow-up, alongside reductions in depression, anxiety, nicotine dependence, and respiratory symptoms.

Published: August 1, 2025
Journal: Journal of Affective Disorders
Authors: Hong, C. J.

Open Accessmeta

Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis

This meta-analysis of 17 trials found that control-group participants in psilocybin depression trials showed markedly smaller improvements (SMC ≈ 0.50) on the MADRS than control participants in SSRI (SMC ≈ 1.00) or esketamine (SMC ≈ 1.12) trials. The authors conclude this disparity may indicate that psilocybin’s antidepressant efficacy is overestimated relative to SSRIs and esketamine, possibly because of functional unblinding and expectancy effects.

Published: July 30, 2025
Journal: JAMA Network Open
Authors: Hieronymus, F., López, E., Lundberg, J., Sjögren, H. W.

Open Accessmeta

Cost-per-remitter for esketamine nasal spray versus quetiapine for treatment-resistant depression

Using ESCAPE-TRD trial data in an Excel-based model, esketamine nasal spray plus an oral antidepressant achieved a 50% remission rate at 32 weeks versus 33% for quetiapine XR plus an oral antidepressant. The model estimated lower cost-per-remitter for esketamine (about $3,102 lower in a commercial setting and $456 lower in Medicaid), suggesting esketamine plus an oral antidepressant is cost‑effective for adults with treatment‑resistant depression.

Published: June 9, 2025
Journal: Journal of Comparative Effectiveness Research
Authors: Bowrey, H. E., Clemens, K., Desai, U., Doran, J., Eid, D., Joshi, K., Kirson, N., Qu, A., Rive, B., Teeple, A.

Clinical Trials

12 trials

Not yet recruitingPhase IV

Ketamine for Postherpetic Neuralgia With Depression

This randomised, double-blind, placebo-controlled Phase IV trial (n=50) will study the effects of a single low-dose intravenous esketamine (0.2 mg/kg; ~14 mg/70 kg over 40 minutes) combined with oral duloxetine (60 mg/day) on depression in patients with postherpetic neuralgia.

Started: June 15, 2025
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT06968624

Enrolling by invitationPhase NA

Assess the Utility of a Speech-based Machine Learning Algorithm to Predict Treatment Response to Psychiatric Interventions

This observational cohort study (n=200) will assess whether a speech-based machine learning algorithm can predict treatment response to psychiatric interventions, specifically repetitive transcranial magnetic stimulation (TMS) and Spravato (esketamine) nasal spray.

Started: February 1, 2025
Type: observational
Randomized: No
Registry ID: NCT06823024

CompletedPhase NA

Esketamine Treatment for Depressive Episodes With Suicidal Ideation in Mood Disorders

Multicentre, randomised, non-inferiority, parallel-group open-label trial (n=340) comparing six adjunctive IV esketamine infusions (0.2 mg/kg, 40-minute infusion, three times/week) versus six ECT sessions over two weeks for reduction of suicidal ideation in depressive episodes.

Started: April 1, 2024
Type: interventional
Blinding: single
Randomized: Yes
Registry ID: NCT06355180

RecruitingPhase III

Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure (INTENSIFY)

This randomized, controlled trial (n=1254) investigates the effect of an intensified pharmacological treatment (including ketamine/esketamine and clozapine) for schizophrenia, major depressive disorder (MDD), and bipolar depression in subjects who experienced a first-time treatment failure on their first-line treatment.

Started: March 31, 2024
Type: interventional
Blinding: single
Randomized: Yes
Registry ID: NCT05603104

Unknown statusPhase NA

Effect of Esketamine on Depressive Symptoms of Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy (EDSOP)

This interventional trial (n=400) investigates the effect of esketamine infusion during laparoscopic sleeve gastrectomy on postoperative depressive symptoms among obese patients.

Started: January 1, 2024
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT06199011

Unknown statusPhase I

Effect of Esketamine on Reducing Postoperative Anxiety and Depression in Adolescent Patients

Double-blind, randomised, controlled perioperative trial (n=200) evaluating a single subanesthetic esketamine dose to reduce postoperative anxiety and depression in adolescents undergoing elective surgery.

Started: October 10, 2023
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT06073015

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Search all Esketamine papers Search all Depressive Disorders trials Full Esketamine profile Full Depressive Disorders profile

Esketamine for Depressive Disorders

Esketamine

Depressive Disorders

Academic Research

Long-term treatment with esketamine nasal spray in patients with treatment resistant depression: Results from the ESCAPE-LTE study

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study

Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial

Efficacy and safety of esketamine for smoking cessation among patients diagnosed with lung cancer and major depression disorder: A randomized, placebo-controlled clinical trial

Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis

Cost-per-remitter for esketamine nasal spray versus quetiapine for treatment-resistant depression

Clinical Trials

Ketamine for Postherpetic Neuralgia With Depression

Assess the Utility of a Speech-based Machine Learning Algorithm to Predict Treatment Response to Psychiatric Interventions

Esketamine Treatment for Depressive Episodes With Suicidal Ideation in Mood Disorders

Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure (INTENSIFY)

Effect of Esketamine on Depressive Symptoms of Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy (EDSOP)

Effect of Esketamine on Reducing Postoperative Anxiety and Depression in Adolescent Patients

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