Esketamine for Depressive Disorders

87 papers and 71 clinical trials exploring esketamine as a treatment for depressive disorders.

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

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

Safety summary

Esketamine for Depressive Disorders: adverse events

Esketamine safety reports for Depressive Disorders most often include dizziness, headache, nausea, paresthesia among the source-backed named adverse events currently normalized in Blossom.

8 source papers|136 named AE rows|Top events: dizziness, headache, nausea

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Dose summary

Esketamine for Depressive Disorders: dose summaries

Esketamine clinical studies for Depressive Disorders include 24 structured dose rows across 20 linked trials. Common source-reported dose patterns include 84 mg, 0.2 mg/kg, 56 mg. Interpret these as descriptive trial protocols, not treatment recommendations.

32 source papers|24 dose rows|Patterns: 84 mg, 0.2 mg/kg, 56 mg

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Academic Research

87 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.

Paywallindividual

Preliminary evidence that serum interleukin-6 is a candidate biomarker of response to esketamine in treatment-resistant depression

This open-label Phase 2 trial (n=14) found that adults with treatment-resistant depression who received intranasal esketamine had improving depression scores over time, and that higher baseline interleukin-6 was linked to faster symptom reduction. Lower interleukin-6 was associated with worse depression and greater disability, while interleukin-6 levels themselves did not change during treatment.

Published: April 24, 2026
Journal: Journal of Psychopharmacology
Authors: Colizzi, M., Morandin, E., Croccia, V., Scipioni, C., Rosada, C., Sepulcri, O., Balestrieri, M., Garzitto, M.

Open Accessindividual

Intranasal esketamine in treatment-resistant depression: long-term dosing patterns and clinical outcomes in a 5-year observational study

This observational study (n=45) followed people with treatment-resistant depression for up to 5 years and found that adjunctive intranasal esketamine was linked with sustained reductions in depression scores in those who stayed on treatment. No hypomania or mania was seen, and side effects were generally low.

Published: April 20, 2026
Journal: Therapeutic Advances in Psychopharmacology
Authors: Cuomo, A., McIntyre, R., Koukouna, D., Pinzi, M., Pardossi, S., Firenzuoli, B., Barillà, G., Carmellini, P., Alamia, A., Fagiolini, A.

Paywallindividual

Esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A real-world longitudinal study of suicidal ideation and self-harm

This multicentre prospective observational study (n=90) found that intranasal esketamine was linked to reduced suicidal thoughts, suicidal behaviour and deliberate self-harm over 6 months in people with treatment-resistant depression, including those with borderline personality disorder. Improvements were seen from 1 month onwards, with no serious adverse events or increase in suicidality.

Published: April 17, 2026
Journal: Asian Journal of Psychiatry
Authors: Raffone, F., Mazzoni, F., De Ciechi, A., Girone, N., Macellaro, M., Martinotti, G., Dell’Osso, B., Olivola, M., Martiadis, V.

Open Accessindividual

Mystical Experience Induced by Esketamine Treatment: A Real-World Observational Study

This observational study (n=45) followed people with treatment-resistant depression receiving esketamine and found that psychedelic-like mystical experiences were common and varied widely between sessions. Higher mystical experience scores, especially positive mood and mystical feelings, were linked with greater improvement in depression symptoms, while dissociation was not.

Published: April 1, 2026
Journal: MedRvix
Authors: Mallevays, M., Fuet, L., Danon, M., Di Lodovico, L., Jaffré, C., Bouzeghoub, L., Mrad, S., Rousselet, A. V., Allary, L., Müh, C., Vissel, B., De Maricourt, P., Vinckier, F., Gaillard, R., Mekaoui, L., Gorwood, P., Petit, A. C., Berkovitch, L.

Clinical Trials

71 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 NA

ATLAS-1: Advanced Trial for Longitudinal Assessment in Salma 1

This observational study (n=5000) will examine adults with depressed mood who are receiving esketamine, conventional rTMS, or SAINT as part of routine care, with the aim of assessing the feasibility and clinical utility of predictive models of treatment response built from multimodal clinical data. It will use integrated real-world datasets to explore whether personalised tools could help guide treatment selection in depression. Participants must be 18 years or older, able to give informed consent, and prescribed one of the listed treatments in standard clinical practice. The main outcome is the Patient Health Questionnaire 9-item (PHQ-9), measured pre-treatment, post-treatment, 2 weeks after treatment, and then monthly for 12 months. Retrospective clinical and research data from existing databases may also be included, where available and authorised, to support model development and validation.

Started: March 25, 2026
Type: observational
Blinding: none
Randomized: No
Registry ID: NCT07528014

Not yet recruitingPhase I

Effect of sub - anesthetic dose of esketamine on the incidence of postoperative anxiety and depression in patients with thyroid cancer and breast cancer: A prospective, single - center clinical study

This prospective, single-centre interventional trial in China (n=196 planned; 98 per group) is a Phase 0 parallel-group study evaluating whether subanaesthetic esketamine reduces postoperative anxiety and depression in adults undergoing surgery for thyroid cancer or breast cancer. Participants are randomised to receive either an esketamine infusion prepared at 2.5 mg/ml and administered at 0.25 mg/kg/h, or 0.9% normal saline at 0.1 ml/kg/h as the control comparator. The study population includes both sexes aged 18 years and older. The primary outcome is the incidence of postoperative anxiety and depression in both groups within 72 hours after surgery. Secondary outcomes include postoperative quality of recovery, assessed using the QoR-15 at 48 hours, postoperative pain scores at 48 and 72 hours, and healthcare utilisation measures including length of hospital stay and total cost from surgery to discharge. The trial is designed to assess whether perioperative esketamine can improve early psychological and recovery outcomes in patients with cancer surgery.

Started: March 20, 2026
Type: interventional
Blinding: none
Randomized: No
Registry ID: ChiCTR2600120238

RecruitingPhase IV

Esketamine With or Without Integration Therapy for Treatment-Resistant Depression

This Phase IV, randomised, single-masked, parallel trial (n=20) will assess whether adding brief, structured preparation and integration therapy to FDA‑approved intranasal esketamine (Spravato®) improves depressive symptoms in adults aged 21–65 with treatment-resistant depression; the primary outcome is change in Montgomery‑Åsberg Depression Rating Scale (MADRS) score from baseline to the end of acute treatment at 8 weeks. Participants will be randomised to receive intranasal esketamine administered under medical supervision per FDA guidelines (twice weekly in weeks 1–4, then weekly or biweekly in weeks 5–8 based on clinical response) with standard post-dose monitoring of at least two hours. The experimental arm also receives brief, manualised preparation and integration sessions delivered by trained clinicians before and after each dosing session; the comparator arm receives esketamine with standard clinical monitoring and psychiatric care only. Key secondary measures include emotional regulation, therapeutic alliance, treatment acceptability and dissociative experiences, with exploratory assessments of participant engagement, perceived coherence of experience and satisfaction. Eligibility includes adults 21–65 with major depressive disorder meeting treatment‑resistance criteria (failure of ≥2 antidepressants) and baseline MADRS ≥30; the study is single-site and lasts approximately 8 weeks per participant.

Started: February 1, 2026
Type: interventional
Blinding: single
Randomized: Yes
Registry ID: NCT07369102

RecruitingPhase I

Subanesthetic Esketamine in Modified ECT for Severe Depression in Adolescents: Clinical and Mechanistic Study

This double-blind trial (n=220) of adolescents with severe depression will modify electroconvulsive therapy with esketamine.

Started: November 25, 2025
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT07247968

RecruitingPhase NA

Virtual Reality-Based Mindfulness as an Adjunct to Treatment as Usual in Treatment-Resistant Depression

This interventional trial (n=30) will evaluate the efficacy and tolerability of a virtual reality-based mindfulness intervention combined with intranasal esketamine treatment compared to esketamine treatment alone in patients with treatment-resistant major depressive disorder (TRD). Participants will be randomly assigned to receive either the combined treatment (esketamine plus mindfulness) or standard esketamine treatment as usual, with the primary aim of assessing reductions in depressive symptoms. During the 4-week induction phase, both groups will receive intranasal esketamine, with the experimental group also participating in a 10-minute virtual reality mindfulness session prior to each treatment. Following this, the maintenance phase will last from weeks 5 to 30, with participants continuing esketamine administration once weekly for four weeks, followed by biweekly sessions. Key outcome measures will include changes in depressive symptom severity, inflammatory blood parameters, tolerability, and the duration of remission, with assessments conducted at baseline, the end of the induction phase, and at 30 and 54 weeks post-treatment.

Started: September 18, 2025
Type: interventional
Blinding: none
Randomized: Yes
Registry ID: NCT07422519

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