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Home/Research/Ketamine/Bipolar Disorder

Ketamine for Bipolar Disorder

87 papers and 38 clinical trials exploring ketamine as a treatment for bipolar disorder.

CompoundArylcyclohexylamine

Ketamine

A dissociative anesthetic with rapid-acting antidepressant properties, widely used in clinical settings for mood and pain disorders.

Full Ketamine 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

87 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

Faster and greater antidepressant response to intravenous ketamine in bipolar compared with unipolar treatment-resistant depression: Diagnostic and sex-related findings from a naturalistic study

This observational study (n=97) examined intravenous ketamine for treatment-resistant unipolar and bipolar depression and found that symptoms improved in both groups, with faster and greater improvement in bipolar depression. Dissociative effects stayed stable overall, and sex differences in antidepressant response were not seen, although women with unipolar depression reported more dissociation at three months.

Published
April 19, 2026
Journal
Psychiatry Research
Authors
Carmellini, P., Fagiolini, A., Pinzi, M., Magno, M., Martella, D., Nicchi, L., Rescalli, M. B., Tarantino, F., Tinturini, R., Scheggi, S., Gualtieri, G., Cuomo, A.
Open Accessindividual

Blood biomarker changes and relationships after low dose oral ketamine treatment for post-traumatic stress disorder (PTSD)

This open-label trial (n=25) found that six weeks of low-dose oral ketamine treatment for PTSD was associated with small but significant decreases in both BDNF and VEGF-A blood biomarkers, which were positively correlated with each other, suggesting these two proteins may interact as part of the biological mechanism behind ketamine's effects on PTSD symptoms.

Published
March 16, 2026
Journal
Psychopharmacology
Authors
Quigley, B. L., Orr, E., Kafka, S., Hajishafiee, M., Bouças, A. P., Wellington, N., Dutton, M., Jones, M., Randall, F., Lagopoulos, J., Can, A. T., Hermens, D. F.
Paywallindividual

Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder

In a subgroup analysis of four adults with treatment-resistant bipolar II disorder, one or two 25 mg psilocybin-assisted psychotherapy sessions produced rapid reductions in depressive symptoms (mean MADRS 32.5 → 20.3 at two weeks, 21.3 at six months). No treatment-emergent mania, hypomania or psychosis was observed, indicating preliminary safety and potential antidepressant efficacy that requires confirmation in larger trials.

Published
February 27, 2025
Journal
Psychedelic Medicine
Authors
Meshkat, S., Kaczmarek, E., Doyle, Z., Brudner, R. M., Gomes, F. A., Blainey, M. G., Weiglein, G., McIntyre, R. S., Mansur, R. B., Rosenblat, J. D.
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

Factors Associated with Antidepressant Effects of Ketamine: A Reanalysis of Double-Blind Randomized Placebo-Controlled Trial of Intravenous Ketamine for Treatment-Resistant Depression

Reanalysis of a placebo‑controlled double‑blind RCT of intravenous ketamine in 31 adults with treatment‑resistant depression found that later age of depression onset predicted a greater antidepressant response three days after infusion, whereas age, sex, baseline severity and dissociative scores showed no association. The authors propose that impaired glutamatergic signalling and reduced neuroplasticity in earlier‑onset cases may explain the diminished ketamine response.

Published
October 16, 2023
Journal
Pharmacopsychiatry
Authors
Yonezawa, K., Uchida, H., Yatomi, T., Ohtani, Y., Nomoto-Takahashi, K., Nakajima, S., Mimura, M., Tani, H., Ac, A.

Clinical Trials

38 trials
Not yet recruitingPhase II

Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder (KET-DBT)

This Phase II randomised, quadruple-masked trial (n=120) will study adults aged 18 to 70 years with borderline personality disorder, treatment-resistant major depressive disorder or bipolar disorder, and suicidal ideation, evaluating whether intravenous ketamine plus dialectical behavioural therapy (DBT) reduces suicidal ideation more rapidly and robustly than midazolam plus DBT. The main purpose is to assess change in suicidal ideation severity from baseline to Day 35 using the Modified Scale for Suicidal Ideation (MSSI). All participants will receive DBT for 6 months, starting before the infusions, with weekly individual sessions and the addition of weekly group sessions from Week 5. The experimental arm will receive six intravenous ketamine infusions over 1 month: the first two at 0.5 mg/kg over 40 minutes, infusions 3 and 4 flexibly dosed at 0.5 mg/kg to 0.75 mg/kg, and infusions 5 and 6 flexibly dosed at 0.5 mg/kg to 0.85 mg/kg. The comparator arm will receive six intravenous midazolam infusions over the same period: the first two at 0.02 mg/kg over 40 minutes, infusions 3 and 4 at 0.02 mg/kg to 0.03 mg/kg, and infusions 5 and 6 at 0.2 mg/kg to 0.035 mg/kg. Participants will also complete hospital visits, remote follow-up by call or videocall, and a range of mood, cognitive and behavioural assessments.

Started
June 1, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07569198
Not yet recruitingPhase II

Feasibility of oral ketamine for bipolar depression: a 20-week open-label study

This open-label Phase II trial (n=30) will investigate the feasibility, safety, and antidepressant effects of oral ketamine (starting at 1 mg/kg, up to 2 mg/kg) in adults with bipolar depression.

Started
June 23, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
ACTRN12625000267459p
CompletedPhase II

FMRI of Patients Receiving IV Ketamine for Treatment Resistant Bipolar Depression

This open-label observational trial (n=20) will investigate the effects of intravenous ketamine on treatment-resistant bipolar depression, with an interventional component of functional magnetic resonance imaging (fMRI).

Started
November 12, 2024
Type
observational
Blinding
none
Randomized
No
Registry ID
NCT06620042
Not yet recruitingPhase III

The Kite Trial: Examining the Effectiveness of Ketamine for Adults with Bipolar Depression

This randomised, double-blind, midazolam-controlled, multicentre trial (n=98) will investigate the efficacy and safety of low-dose subcutaneous ketamine in adults with bipolar depression.

Started
June 28, 2024
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
ACTRN12624000789561
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
Active not recruitingPhase III

Predictors of Intravenous Ketamine Response in TRD

Randomized, double-blinded, midazolam-controlled crossover trial (n=40) testing single IV ketamine (0.5 mg/kg over 40 minutes) versus midazolam (30 µg/kg) in treatment-resistant depression to identify predictors of rapid and sustained response.

Started
January 19, 2024
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT05625555

Explore further

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