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Home/Research/Esketamine/Bipolar Disorder

Esketamine for Bipolar Disorder

9 papers and 6 clinical trials exploring esketamine as a treatment for bipolar disorder.

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
Indication45 million worldwide

Bipolar Disorder

Bipolar disorder, characterised by extreme fluctuations in mood, is a complex mental health condition that affects approximately 45 million people worldwide. Current research on psychedelics as a potential treatment is limited due to concerns about inducing manic episodes, but emerging evidence, particularly regarding ketamine, suggests promise for alleviating depressive symptoms associated with the disorder.

Full Bipolar Disorder profile

Academic Research

9 papers
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

Early effects predict trajectories of response to esketamine in treatment-resistant depression

This longitudinal study (n=50, confirmatory sample n=55) investigated the use of esketamine in patients with treatment-resistant depression (TRD) and aimed to define distinct response trajectories. The study identified two classes, one representing response and the other non-response, influenced by factors like concomitant benzodiazepine medication, number of depressive episodes, or polarity. After two esketamine administrations, the depression score (MADRS) predicted the 90-day response trajectory with 80% accuracy, suggesting clinicians could use MADRS scores to decide whether to continue treatment in TRD patients.

Published
December 1, 2023
Journal
Journal of Affective Disorders
Authors
Estrade, I., Petit, A. C., Sylvestre, V., Danon, M., Leroy, S., Perrain, R., Vinckier, F., Mekaoui, L., Gaillard, R., Advenier-Iakovlev, E., Letizia Mancusi, R., Poupon, D., De Maricourt, P., Gorwood, P.
Open Accessindividual

Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder

In this single-centre pilot randomised, double-blind trial of 30 adults with major depressive disorder and fluctuating antidepressant response, a single subanaesthetic intravenous dose of esketamine (0.2 mg/kg) added to ongoing oral antidepressants produced markedly higher 2-week response rates (66.7% vs 6.7%) and greater reductions in MADRS scores than midazolam. No serious adverse events, psychotomimetic effects, or clinically significant manic symptoms were observed.

Published
August 14, 2023
Journal
JAMA Network Open
Authors
Xiao, C., Zhou, J., Zhu, X., Liu, J., Deng, Q., Wang, G., Wang, H., Hu, Y., Li, A.
Open Accessindividual

Treating Bipolar Depression with Esketamine: Safety and Effectiveness data from a naturalistic multicentric study on Esketamine in Bipolar versus Unipolar Treatment-Resistant Depression

This open-label study (n=70) compared the effect of esketamine (28-84mg; 8x) in those with bipolar treatment-resistant depression (B-TRD, n=35) and those with unipolar TRD. There was no significant difference between the two groups on depression scores, and both responded to treatment. Those in the B-TRD group had more anxiety-reducing effects. This study is part of the REAL-ESK study.

Published
January 13, 2023
Journal
Bipolar Disorders An International Journal of Psychiatry and Neurosciences
Authors
McIntyre, R. S.
Paywallindividual

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression

This open-label study (n=70) on suicidal ideation (SI) in patients with major depressive disorder (MDD) and bipolar depression (BD) finds that esketamine (1x p/w 6ws) led to significant reductions in SI at the end of the study (24h after last administration). There was no statistically significant difference between the two subpopulations.

Published
August 31, 2022
Journal
Clinical Drug Investigation
Authors
Surjan, J., Grossi, J. D., Del Porto, J. A., Delfino, S. R., De Oliveira Cerqueira, R., Lucchese, C., Magalhães, E., Del Sant, L. C., Tuena, M. A., Nakahira, C., Fava, V. A. R., Steglich, M., Abdo, G. L., Barbosa, M. G., Sarin, L. M., Lacerda, A. L. T.
Paywallmeta

Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis

This meta-analysis (n=2,801) explored the association between baseline levels and longitudinal changes in blood-based biomarkers, and response to ketamine/esketamine. Over 460 individual biomarkers were examined and there were no consistent associations between baseline levels of blood-based biomarkers, and response to ketamine. However, a longitudinal analysis revealed ketamine responders had statistically significant increases in brain-derived neurotrophic factor (BDNF) when compared to pre-treatment.

Published
June 27, 2022
Journal
Molecular Psychiatry
Authors
Medeiros, G. C., Gould, T. D., Prueitt, W. L., Nanavati, J., Grunebaum, M. F., Farber, N. B., Singh, B., Selvaraj, S., Machado-Vieira, R., Achtyes, E. D., Parikh, S. V., Frye, M. A., Zarate, C. A., Goes, F. S.

Clinical Trials

6 trials
Enrolling by invitationPhase NA

Assess the Utility of a Speech-based Machine Learning Algorithm to Predict Treatment Response to Psychiatric Interventions

This observational cohort study (n=200) will assess whether a speech-based machine learning algorithm can predict treatment response to psychiatric interventions, specifically repetitive transcranial magnetic stimulation (TMS) and Spravato (esketamine) nasal spray.

Started
February 1, 2025
Type
observational
Randomized
No
Registry ID
NCT06823024
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

Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure (INTENSIFY)

This randomized, controlled trial (n=1254) investigates the effect of an intensified pharmacological treatment (including ketamine/esketamine and clozapine) for schizophrenia, major depressive disorder (MDD), and bipolar depression in subjects who experienced a first-time treatment failure on their first-line treatment.

Started
March 31, 2024
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
NCT05603104
RecruitingPhase NA

University of Iowa Interventional Psychiatry Service Patient Registry

Prospective observational registry (n=1000) collecting biomarker and clinical outcome data from patients receiving ECT, TMS/dTMS, racemic ketamine infusions, or intranasal esketamine for treatment‑resistant depression and OCD.

Started
November 2, 2020
Type
observational
Blinding
none
Randomized
No
Registry ID
NCT04480918
Unknown statusPhase NA

The Effect of S-ketamine for Patients Undergoing Electroconvulsive Therapy (ECT)

Randomised, quadruple-blind, factorial trial (n=150) comparing S-ketamine 0.25 mg/kg and ketamine 0.5 mg/kg versus propofol+saline during ECT in adults with depressive disorders to evaluate short-term efficacy and safety.

Started
August 1, 2020
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT04399070
CompletedPhase II

A multicentre, double-blind, randomised, placebo - controlled phase II study to assess efficacy, safety and pharmacokinetics of inhaled Esketamine in subjects with treatment-resistant bipolar depression

Double-blind, randomised, placebo-controlled Phase II trial (n=88) in Poland testing inhaled esketamine (inhalation powder) versus placebo in adults 18–65 with treatment-resistant bipolar depression to assess efficacy, safety and pharmacokinetics.

Started
July 30, 2018
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
2018-002669-20

Explore further

Search all Esketamine papers Search all Bipolar Disorder trials Full Esketamine profile Full Bipolar Disorder profile