Ketamine for Depressive Disorders

400 papers and 320 clinical trials exploring ketamine as a treatment for depressive disorders.

CompoundArylcyclohexylamine

Ketamine

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

Full Ketamine 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

Ketamine for Depressive Disorders: adverse events

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

26 source papers|278 named AE rows|Top events: dizziness, headache, nausea

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Dose summary

Ketamine for Depressive Disorders: dose summaries

Ketamine clinical studies for Depressive Disorders include 118 structured dose rows across 79 linked trials. Common source-reported dose patterns include 0.5 mg/kg, 0.5-0.75 mg/kg, 0.25 mg/kg. Interpret these as descriptive trial protocols, not treatment recommendations.

155 source papers|118 dose rows|Patterns: 0.5 mg/kg, 0.5-0.75 mg/kg, 0.25 mg/kg

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Academic Research

400 papers

Paywallindividual

Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial

This pilot trial (n=16) tested psilocybin-assisted cognitive behavioural therapy for adults with major depressive disorder, using 10 mg and 25 mg psilocybin doses alongside 12 therapy sessions. It was well accepted and feasible, with no serious adverse events, and most participants improved in depressive symptoms, with gains lasting three months after treatment.

Published: June 8, 2026
Journal: Journal of Affective Disorders
Authors: Weintraub, M. J., Jeffrey, J. K., Ichinose, M. C., Bergman, R. L., Shapiro, B., Barnett, G., Artin, H., Lynn, M., Salimian, A., Grody, S., Ramesh, R., Eales, L., Grob, C. S., Miklowitz, D. J.

Paywallindividual

A pilot randomized trial of ketamine for suicidal ideation in a pediatric emergency department

This triple-blind randomised controlled trial (n=15) in adolescents with suicidal ideation in a paediatric emergency department tested whether intravenous ketamine, midazolam or saline could be studied feasibly and safely. Recruitment and follow-up were good, blinding seemed effective, and no serious or unexpected adverse events occurred.

Published: June 3, 2026
Journal: Canadian Journal of Emergency Medicine
Authors: Onikashvili, Y., Burt, H., Meckler, G., Bone, J. N., Hind, T., Sih, K., Sassi, R., Stillwell, K., Black, T., Doan, Q.

Open Accessindividual

Low-Dose Buprenorphine Following Ketamine Treatment for Suicidal Ideation in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

This randomised, double-blind, placebo-controlled trial (n=50) tested low-dose sublingual buprenorphine after ketamine in adults with major depressive disorder and suicidal thoughts. Buprenorphine led to a greater and longer-lasting reduction in suicidal ideation than placebo, while depression scores were similar and no serious treatment-related side effects occurred.

Published: May 18, 2026
Journal: American Journal of Psychiatry
Authors: Tucciarone, J. M., Bandeira, I. D., Blasey, C., Kratter, I. H., Ehrie, J., Keller, J., Pankow, H., Chang, M., Hawkins, J., Evers, A. G., Bernert, R., DeBattista, C., Truong, H., Rodriguez, C. I., Heifets, B. D., Schatzberg, A. F.

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Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Trial

This open-label single-arm trial (n=20) found that a single 25 mg dose of psilocybin with psychological support was linked to rapid and lasting reductions in chronic suicidal thoughts and depression over 12 weeks. No serious adverse events were reported.

Published: May 13, 2026
Journal: Journal of Clinical Psychiatry
Authors: Vaart, A. V. D., LaPratt, J., Swartz, K., Shoultz, A., Lauterbach, M., Suppes, T., Sackeim, H. A., Aaronson, S. T.

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Intranasal Ketamine for Existential Distress in Advanced Cancer

This secondary analysis of the INKeD-PC trial (n=15) found that three doses of intranasal racemic ketamine in patients with advanced cancer receiving palliative care led to clinically meaningful improvements in existential distress, anxiety, symptom burden, and quality of life, with psychological symptoms improving more than physical ones.

Published: April 27, 2026
Journal: Journal of Pain and Symptom Management
Authors: Aguiar, S., Makarious, M., Lipsitz, O., deVries, F. E., Doyle, Z., McIntyre, R. S., Rodin, G., Zimmermann, C., Mak, E., Hannon, B., Schulz-Quach, C., Al Kindy, A., Patel, Z., Rosenblat, J. D., Li, 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.

Clinical Trials

320 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

RecruitingPhase NA

Coaching as an Adjunct to Ketamine Therapy for Treatment-Resistant Depression

This non-randomised, single-group interventional trial (n=20) will assess the feasibility and acceptability of adding psychedelic integration coaching to ongoing maintenance ketamine treatment in adults with treatment-resistant depression (TRD). The study will enrol participants already receiving maintenance intravenous ketamine or intranasal esketamine at Massachusetts General Hospital and aims to explore whether coaching can support symptom improvement and personal growth alongside existing treatment. Participants will receive 12 weekly, 50-minute one-on-one coaching sessions delivered via Zoom by trained psychedelic integration coaches. The coaching is non-clinical, collaborative and participant-directed. Over the 3-month coaching period, and again at a 1-month follow-up, participants will attend monthly study visits with brief remote assessments by a study clinician and self-report questionnaires, with visits taking about 1 to 2 hours depending on the time point. The primary outcomes are feasibility and acceptability from enrolment through Month 3.

Started: April 1, 2026
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT07563868

RecruitingPhase II

A Clinical Trial of Add-on Oral Slow-release Ketamine Treatment in Major Depression

This Phase II, open-label trial (n=12) will evaluate the efficacy of Ketamine Hydrochloride Prolonged-Release Tablets (KET01, 240 mg) as an adjunctive treatment during the initiation of standard antidepressant therapy in adults with Major Depressive Disorder (MDD). The primary aim is to determine whether the addition of ketamine can reduce depressive symptoms after one week of treatment, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Participants will receive four doses of KET01 over eight days, starting concurrently with a newly prescribed conventional antidepressant. Throughout the treatment week, patients will complete various questionnaires and rating scales, and blood samples will be collected at five visits to monitor side effects and identify potential biomarkers. Following the one-week ketamine treatment, participants will continue with the standard antidepressant therapy, with a follow-up period extending for an additional three weeks. The trial is set to commence in March 2026 and conclude by October 2026.

Started: March 1, 2026
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT07396272

Not yet recruitingPhase NA

Neural Mechanisms of Ketamine Antidepressant Treatment 2.0: Exploring how ketamine affects the brain function in people with difficult-to-treat depression.

This is a randomised, quadruple‑blind, placebo‑controlled mechanistic clinical trial enrolling 90 participants (60 adults with major depressive disorder, including treatment‑resistant cases, and 30 healthy controls) at the Royal Melbourne Hospital, Australia, with recruitment from February 2026 and completion expected December 2027. Participants receive a single subcutaneous administration of ketamine 0.75 mg/kg versus placebo (0.9% saline). The primary outcome is change in habenula activity measured using ultra‑high‑field 7T MRI at baseline and 24–48 hours after dosing, designed to probe rapid neural mechanisms underlying ketamine’s antidepressant effects. Secondary outcomes assess clinical and behavioural effects using the Montgomery–Åsberg Depression Rating Scale (MADRS), QIDS‑C, Snaith–Hamilton Pleasure Scale (SHAPS), GAD‑7, and objective activity monitoring by actigraphy. The protocol includes healthy controls to facilitate mechanistic comparisons between clinical and non‑clinical neural responses. The study phase is not specified in the available data. The quadruple‑blind design and saline comparator aim to isolate drug‑specific neural changes and early clinical signal following a single subcutaneous ketamine exposure in treatment‑resistant and broader MDD populations.

Started: February 2, 2026
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: ACTRN12625001087448

Not yet recruiting

Mitochondrial Function After Ketamine

This observational study will assess the impact of esketamine treatment on mitochondrial function in individuals with Treatment-Resistant Depression (n=30). The primary aim is to investigate how esketamine influences mitochondrial parameters in peripheral blood cells, including mitochondrial content and circulating biomarkers such as GDF15, and to determine if these changes can serve as predictors or monitors of clinical response to the treatment. Participants will be evaluated at baseline, 3 hours after the initial esketamine inhalation, and again 6 weeks post-treatment. Eligible individuals are aged 18 to 65, diagnosed with Major Depressive Disorder, and have not responded to at least two prior antidepressant trials. Exclusion criteria include known sensitivities to ketamine, certain medical conditions, and concurrent use of specific medications. The study is sponsored by Sheba Medical Center and is expected to commence in February 2026, with completion anticipated by January 2028.

Started: February 1, 2026
Type: interventional
Randomized: No
Registry ID: NCT07399756

RecruitingPhase III

A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder (AVENUE)

This Phase III, double-blind, randomised, placebo-controlled trial (n=258) will evaluate the efficacy and safety of intranasal esketamine 84 mg in addition to comprehensive standard of care for rapidly reducing symptoms of major depressive disorder (MDD) in adolescent participants aged 12 to 17 with acute suicidal ideation or behaviour. The primary outcome is the change in depressive symptoms measured by the Children's Depression Rating Scale - Revised (CDRS-R) total score at 24 hours post-first dose. Participants will be randomly assigned to receive either intranasal esketamine (84 mg, with potential dose adjustments to 56 mg) plus oral placebo or intranasal placebo plus oral midazolam (0.0625 mg/kg) twice weekly for four weeks. The treatment will occur on specific days, with assessments conducted to monitor the efficacy and safety of the interventions. The trial is sponsored by Janssen Research & Development, LLC, with an estimated start date of January 8, 2026, and a completion date of September 15, 2031.

Started: January 8, 2026
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT07227454

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