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Home/Research/Esketamine/Suicidality

Esketamine for Suicidality

43 papers and 12 clinical trials exploring esketamine as a treatment for suicidality.

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
IndicationMore than 727,000 deaths by suicide worldwide each year

Suicidality

Suicidality covers the spectrum of suicidal thoughts, plans and behaviours, and it contributes to more than 727,000 deaths worldwide each year. The strongest evidence for rapidly reducing suicidal thinking is for ketamine and esketamine, and esketamine carries a specific regulatory approval. But even there, a reduction in suicide itself has not been proven, and classic psychedelics remain unproven for suicidality and can carry real risks for people in crisis. This is a research summary, not medical advice.

Full Suicidality profile

Academic Research

43 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.
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

Intranasal esketamine: real-world clinical practice in treatment-resistant depression and factors associated with treatment response

This retrospective study (n=101) of inpatients with treatment-resistant depression (TRD) found that intranasal esketamine led to significant reductions in depression severity, with 28.8% achieving response and 19.3% remission. Older age was associated with greater remission likelihood, and extended induction beyond eight sessions appeared particularly beneficial for older patients and those with psychiatric comorbidities, with no serious adverse events observed.

Published
March 17, 2026
Journal
BMC Psychiatry
Authors
Baune, B. T., Rosemann, K., Hefter, D., Tonkul, M., Kavakbasi, E.
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.

Clinical Trials

12 trials
Enrolling by invitationPhase NA

Psychotherapy Combined With Intranasal Esketamine for the Treatment of Suicidal Ideation

This interventional trial (n=56) will evaluate the effects of combined intranasal esketamine and brief cognitive behavioural therapy for suicide prevention (BCBT-SP) in patients experiencing suicidal ideation associated with treatment-resistant depression (TRD). The primary aim is to assess reductions in suicidal ideation at one week post-treatment, comparing the combined treatment group with a control group receiving only intranasal esketamine. Participants aged 18 to 70 with a major depressive episode and ongoing suicidal ideation will be recruited. The trial will consist of two arms: one receiving naturalistic intranasal esketamine and the other receiving BCBT-SP alongside intranasal esketamine, involving 12 weekly sessions of psychotherapy. Key outcome measures include the Beck Scale for Suicidal Ideation and TMS-EEG N100 peak, both assessed one week after treatment. The study is set to begin in January 2026 and is expected to complete by January 2029.

Started
January 9, 2026
Type
interventional
Blinding
none
Randomized
Yes
Registry ID
NCT07396220
Not yet recruitingPhase IV

Controlled study of esketamine treatment for depression with suicidal ideation based on near-infrared spectroscopy

This parallel, controlled Phase 4 trial (n=60) in China is evaluating intravenous esketamine for adults with depression and suicidal ideation. Participants are allocated to an observation group receiving esketamine infusion or a control group treated with a selective serotonin reuptake inhibitor (SSRI). The study is designed to assess the clinical effects of esketamine in this high-risk population, with outcomes measured using the Hamilton Rating Scale for Depression (HAMD-17) and the Columbia-Suicide Severity Rating Scale (C-SSRS). These primary outcomes focus on changes in depressive symptoms and suicidality, although the specific assessment timepoints are not provided in the trial record. A secondary outcome is frontal lobe oxygenated haemoglobin concentration measured by near-infrared brain imaging, suggesting an interest in correlating symptomatic improvement with changes in cerebral haemodynamics. The trial is sponsored by Huzhou Third Municipal Hospital. As a registered Chinese interventional study, it adds to the growing body of clinical research examining esketamine as a rapid-acting treatment option for depression with suicidal ideation.

Started
February 1, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
ChiCTR2500095899
Not yet recruitingPhase IV

Investigating the Efficacy and Pharmacokinetic Profiles of Esketamine at Various Doses for Adolescents with Depression and Suicidal Ideation

This parallel Phase 4 interventional trial in China (n=180) is evaluating the efficacy and pharmacokinetic profiles of esketamine at different doses in adolescents aged 13 to 17 years with depression and suicidal ideation. Participants are allocated to one of three intravenous esketamine groups or a saline control group: low-dose esketamine hydrochloride 0.25 mg/kg, medium-dose 0.375 mg/kg, or high-dose 0.50 mg/kg, each diluted in 50 ml of 0.9% sodium chloride injection and administered by intravenous infusion, versus 50 ml of 0.9% sodium chloride injection alone. The primary outcomes are suicide risk and ideation, measured using the Columbia Suicide Severity Rating Scale (C-SSRS) and the Scale for Suicide Ideation (SSI), with assessment timepoints not specified in the available record. Secondary outcomes include depressive symptoms, anxiety, diagnostic status, cognitive and global functioning, dissociative and manic symptoms, and neuroimaging, assessed using instruments such as the MADRS, HAMA, SCID, CDI, BPRS, YMRS, CADSS, GAF, cognitive testing, and MRI. The study is sponsored by the Affiliated Brain Hospital of Guangzhou Medical University.

Started
January 20, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
ChiCTR2500095496
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
Not yet recruitingPhase IV

The efficacy, safety and mechanism of esketamine vs electroconvulsive therapy in the treatment of suicidal risk of patients with major depressive episode

This Phase 4, parallel interventional trial in China (n=300) is comparing intravenous esketamine with modified electroconvulsive therapy (MECT) for patients with a major depressive episode and suicidal ideation. Participants are allocated to an esketamine group receiving intravenous infusion of esketamine 0.5 mg/kg or to an MECT group receiving MECT. The study includes adolescents and adults aged 13 to 85 years, with both sexes eligible. The primary outcome is change in suicidal ideation, assessed using the Beck Scale for Suicide Ideation. Secondary outcomes include depressive and anxiety symptoms, anhedonia, and dissociative effects, measured with the Montgomery–Åsberg Depression Rating Scale, Hamilton Depression Scale, Hamilton Anxiety Scale, Snaith-Hamilton Pleasure Scale, Dimensional Anhedonia Rating Scale, and the Clinician Administered Dissociative States Scale. The trial is designed to evaluate not only clinical efficacy and safety, but also potential mechanisms underlying the anti-suicidal effects of esketamine relative to MECT. Sponsored by The Affiliated Brain Hospital of Guangzhou Medical University, this study reflects ongoing clinical research in China into rapid-acting interventions for acute suicidal risk in major depressive episodes.

Started
May 23, 2023
Type
interventional
Blinding
none
Randomized
No
Registry ID
ChiCTR2300071697
RecruitingPhase NA

IV Ketamine Vs. in Esketamine for MDD TRD

Prospective observational cohort (n=80) comparing acute treatment courses of IV ketamine (0.5 mg/kg infusion) versus IN esketamine (56 mg then 84 mg) in adults with treatment-resistant major depressive disorder and suicidal ideation.

Started
March 20, 2023
Type
observational
Blinding
none
Randomized
No
Registry ID
NCT06488586

Explore further

Search all Esketamine papers Search all Suicidality trials Full Esketamine profile Full Suicidality profile