Papers

Research literature with structured metadata.

Trials

Registered studies by status, phase, and compound.

Topics

Indications and themes psychedelics are researched for.

Compounds

Evidence across molecules with rich data.

Countries

Regulation, access, and research activity by region.

Stakeholders

Organizations shaping the space across research, policy, and funding.

People

Investigators, clinicians, and authors with mapped output.

Courses

Training programs and certifications across modalities.

Events

Conferences, workshops, and convenings by date and focus.

Results

Compare outcome data across trials and publications.

Research Snapshot

One-page overview of trials, participants, papers, and research networks.

Clinical Guidelines

Trial-anchored manuals and protocol guidance with competency mapping.

Research recaps

Monthly evidence summaries with key takeaways.

Map of research

Landscape view of trials, compounds, and outcomes.

Newsletter

Weekly or daily updates on trials, publications, analysis, and more.

Research Groups

Worldwide map of psychedelic research centres by region.

Road to Access

Science, regulation, and economics on the path to patient access.

Research Network

Interactive co-authorship map of psychedelic researchers.

Top papers

Find needles in the haystack of psychedelic research per topic.

AskBeta
Pricing

The intelligence layer for psychedelic research.

Company

  • About
  • Contact
  • Newsletter

Product

  • Feedback
  • Roadmap
  • Changelog
  • API
  • Partners
  • Clinical Guidelines

Legal

  • Privacy
  • Terms

© 2026 Blossom. All rights reserved.

Home/Research/Esketamine/Major Depressive Disorder (MDD)

Esketamine for Major Depressive Disorder (MDD)

60 papers and 40 clinical trials exploring esketamine as a treatment for major depressive disorder (mdd).

Compounddissociative

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
IndicationOver 264 million worldwide.

Major Depressive Disorder (MDD)

Major Depressive Disorder (MDD) represents a significant mental health challenge, with emerging research into the efficacy of psychedelics like psilocybin and ketamine offering new avenues for treatment. Recent studies have demonstrated the potential of these compounds to alleviate symptoms, particularly in treatment-resistant cases of MDD.

Full Major Depressive Disorder (MDD) profile

Academic Research

60 papers
Paywallindividual

Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention: The CBT-ENDURE Randomized Trial

This randomised trial (n=93) found that adding 16 weeks of cognitive behavioural therapy to esketamine was feasible for people with major depression and suicidal ideation, and it reduced suicidal thoughts and depression scores more than esketamine with usual care alone. No difference was seen in suicide-related events.

Published
May 4, 2026
Journal
Journal of Clinical Psychiatry
Authors
Wilkinson, S. T., Kitay, B. M., Macaluso, M., Santucci, M. C., Kumpf, K., Voghell, C., Astorino, L., Hershenberg, R., Martinez-Kaigi, V., Nowell, T., Thase, M. E., Sanacora, G., Rhee, T. G.
Open Accessindividual

Repeated intranasal esketamine augmentation in treatment-resistant obsessive-compulsive disorder with comorbid major depressive disorder: a prospective case series

This prospective case series (n=8) examined repeated intranasal esketamine for people with treatment-resistant obsessive-compulsive disorder and comorbid major depressive disorder, and found clear improvement in depression and a smaller, more variable reduction in obsessive-compulsive symptoms. Depression improved earlier than OCD symptoms, and half of the participants met response criteria for each condition.

Published
April 26, 2026
Journal
BMC Psychiatry
Authors
López-Rodríguez, S., Segalàs, C., Real, E., Urretavizcaya, M., Bertolín, S., Menchón, J. M., del Pino Alonso, M.
Open Accessindividual

Effectiveness and factors associated with esketamine response during the 4-week induction period for treatment-resistant depression: post-hoc analysis of the real-world ESKALE study

This post-hoc analysis (n=128) of the French real-world ESKALE study found that intranasal esketamine produced a rapid and steadily increasing antidepressant response in patients with treatment-resistant depression over four weeks (response rate rising from 19% at week one to 47% at week four), and that experiencing dissociation during the first week of treatment may be an early indicator of a positive response.

Published
March 10, 2026
Journal
Journal of Psychiatric Research
Authors
Samalin, L., Rothärmel, M., Mekaoui, L., Sauvaget, A., Wicart, C., Gaudre-Wattine, E., Cohignac, V., Malatesta, A., Dupin, J.
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., Godinov, Y., Haggström, L., Kambarov, Y., Nielsen, R., Oliveira-Maia, A., von Holt, C., Cubała, W., Young, A. H., DJ, Fu.
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
Kosik-Gonzalez, C., Chen, L. N., Lane, R., Bloch, M. H., DelBello, M., Moreno, C., Drevets, W. C., Canuso, C. M., Fu, D. J.
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
Janik, A., Qiu, X., Lane, R., Popova, V., Drevets, W. C., Canuso, C. M., Macaluso, M., Mattingly, G. W., Shelton, R. C., Zajecka, J. M., Fu, D. J.

Clinical Trials

40 trials
Not yet recruitingPhase NA

Multimodal Pharmacological Study of Clinical Cohorts for Major Depressive Disorder

This observational cohort study (n=130) will assess neurobiological changes in adults with major depressive disorder (MDD) and high suicidal risk during rapid antidepressant treatment, with a focus on suicidal tendency and the mechanisms of fast-acting antidepressant effects. Participants will be followed across electroconvulsive therapy (ECT), esketamine nasal spray, or conventional antidepressant treatment paths, with the main outcome being change in Hamilton Depression Rating Scale (HAMD-17) total score from baseline to follow-up. The study will collect data at three time points: baseline, 24 hours after the first treatment, and at remission 4–6 weeks later, with overall treatment follow-up to 8 weeks. It will compare a cohort of 70 patients receiving ECT, 30 receiving esketamine, and 30 receiving conventional medication, while also integrating clinical scales such as the C-SSRS and QIDS-SR16 with multimodal measures including whole genome sequencing, single-cell sequencing, proteomics, metabolomics, DNA methylomics, gut metagenomics, fMRI, DTI, and 32-channel resting-state EEG. Eligible participants are adults aged 18–65 years with DSM-5 MDD and suicidal ideation.

Started
May 30, 2026
Type
observational
Blinding
none
Randomized
No
Registry ID
NCT07602153
RecruitingPhase IV

A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression

This open-label, single-arm Phase IV trial (n=47) will evaluate the efficacy and safety of esketamine nasal spray (flexibly dosed at 56mg or 84mg) in Korean adults with treatment-resistant depression (TRD).

Started
June 9, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT07053345
RecruitingPhase III

PCORI Comparative Effectiveness Study-Esketamine (Spravato) Vs. Ketamine-Equivalence Study

Phase III, randomised, open-label, non-inferiority study (n=400) comparing IV racemic ketamine (up to 60 mg per infusion, max 8 lifetime doses) versus intranasal esketamine (56–84 mg per dose) for treatment-resistant depression.

Started
December 1, 2024
Type
interventional
Blinding
none
Randomized
Yes
Registry ID
NCT06713616
TerminatedPhase NA

Behavioural Activation Therapy and Esketamine for Resistant Depression

Randomised, parallel-arm trial (n=6 actual) comparing concurrent behavioural activation therapy plus intranasal esketamine versus esketamine alone for treatment-resistant depressive episodes in MDD or BD.

Started
June 1, 2024
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
NCT06431386
RecruitingPhase III

The Effect of a Four Week Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment. (INTENSIFY MDD)

Open-label, randomised, parallel trial with blinded raters (n=418) comparing early-intensified pharmacological treatment including esketamine or ketamine (twice-weekly for 4 weeks) plus a second-line antidepressant versus treatment as usual in adults (18–65) with MDD and first-line treatment failure.

Started
March 31, 2024
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
NCT05973851
CompletedPhase II

A Study of CLE-100 (Oral Esketamine) as an Adjunctive Treatment to Standard Antidepressants for Major Depressive Disorder (SOLEO)

Double-blind, randomized, placebo-controlled Phase II outpatient trial (n=90) evaluating CLE-100 (oral esketamine) 1 tablet once daily adjunctive to standard antidepressant therapy for 4 weeks in adults with MDD and inadequate response to ≥2 antidepressants.

Started
March 18, 2024
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT06340958

Explore further

Search all Esketamine papers Search all Major Depressive Disorder (MDD) trials Full Esketamine profile Full Major Depressive Disorder (MDD) profile