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Home/Research/Esketamine/Safety & Risk Management

Esketamine for Safety & Risk Management

39 papers and 5 clinical trials exploring esketamine as a treatment for safety & risk management.

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
IndicationMental health disorders affect over 900 million people worldwide, with conditions like PTSD and depression being among the most prevalent.

Safety & Risk Management

Safety and risk management in psychedelic therapy remains a critical area of research, necessitating vigilant assessment of potential adverse effects as clinical usage expands. Current efforts focus on ensuring that therapeutic practices minimise harm while maximising efficacy for a range of conditions.

Full Safety & Risk Management profile

Academic Research

39 papers
Open Accessindividual

Role of concomitant benzodiazepines, lithium, and lamotrigine in modulating the antidepressant effects of subcutaneous esketamine in patients with treatment-resistant depressive episodes: A retrospective naturalistic study

This retrospective naturalistic study (n=178) examined whether benzodiazepines, lithium or lamotrigine altered the antidepressant effects of subcutaneous esketamine in people with treatment-resistant depression. Depression scores fell over six weeks, but benzodiazepine use was linked to higher symptom levels during treatment, while lithium and lamotrigine were not.

Published
March 31, 2026
Journal
Journal of Affective Disorders
Authors
Atidio, J. P., Delfino, R. S., Garios, I. S., de Brito, C. S. G. F., Gerheim, Y. P., de Almeida e Vasconcelos, G. M., Piloto, R., Ferro, M. D., de Souza Júnior, R. O. P., Surjan, J. C., Lacerda, A. L.
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.
Paywallindividual

Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval

This real-world safety analysis of esketamine in the United States (n=58,483 patients, 1,486,213 treatment sessions over 58 months) found that sedation, dissociation, and increased blood pressure occurred in 34.7%, 41.0%, and 0.9% of sessions respectively, with serious adverse events in <0.1-0.18% of sessions, suicide rates lower than background rates, and 210 cases of abuse/misuse reported, confirming the established safety profile with no new safety signals identified.

Published
October 1, 2025
Journal
American Journal of Psychiatry
Authors
Sanacora, G., Ahmed, M., Brown, B., Cabrera, P., Doherty, T., Himedan, M., Kern, D. M., Lim, L., Lopena, O., Naranjo, R. R., Nuamah, I., Sarayani, A., Turkoz, I., Bowrey, H. E.
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

5 trials
CompletedPhase I

KF2024#1-trial: Esketamine Interaction Study

This open-label, Phase I trial (n=12) will investigate the effects of different methods of esketamine administration (28 mg nasal spray vs. 28 mg oral solution) with and without CYP3A4 inhibitors (grapefruit juice or cobicistat) on drug absorption and metabolism.

Started
December 9, 2024
Type
interventional
Blinding
none
Randomized
Yes
Registry ID
NCT06726382
CompletedPhase NA

The Effect of Esketamine on Sleep Disturbance

Randomised, triple-blind, parallel-group trial (n=204) testing a single 0.2 mg/kg IV esketamine injection versus 5 ml 0.9% saline in females undergoing surgical abortion with sleep disturbance.

Started
May 3, 2024
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06388824
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
CompletedPhase NA

Effect of Intravenous S-ketamine on Opioid Consumption

Randomised, multicentre, parallel-group, quadruple-blind trial (n=345) comparing placebo, low-dose S-ketamine (0.5 mg/kg bolus + 2 µg/kg/min infusion) and high-dose S-ketamine (0.5 mg/kg bolus + 4 µg/kg/min infusion) on intraoperative sufentanil consumption in female breast cancer surgery patients.

Started
October 7, 2021
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT05060068
CompletedPhase I

A Phase I Randomized, Placebo Controlled, Double-Blind, Single-Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PCN-101 (Arketamine) and a Relative Safety Comparison of PCN-101 and Esketamine in Healthy Volunteers

Phase I, randomized, double-blind, placebo-controlled study in healthy volunteers assessing single ascending IV doses of PCN-101 (arketamine) and a crossover relative safety comparison with esketamine (15 mg IV).

Started
February 25, 2020
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
ACTRN12620000226909

Explore further

Search all Esketamine papers Search all Safety & Risk Management trials Full Esketamine profile Full Safety & Risk Management profile