Esketamine for Major Depressive Disorder (MDD)

1 paper and 38 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.

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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

1 paper

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.

Clinical Trials

38 trials

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

Active not recruitingPhase 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

RecruitingPhase NA

The OBSERVE Protocol

This observational cohort study (n=450) will compare the long-term effectiveness, safety, and patient satisfaction of intravenous (IV) ketamine versus intranasal esketamine (Spravato) for treating major depressive disorder (TRD).

Started: January 21, 2024
Type: observational
Randomized: No
Registry ID: NCT06725277

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