Ketamine for Depressive Disorders

402 papers and 322 clinical trials exploring ketamine as a treatment for depressive disorders.

Blossom tracks 402 papers and 322 clinical trials examining ketamine as a treatment for depressive disorders. Ketamine acts primarily as a nmda receptor antagonist. The papers and trials below are sorted by recency, and reported adverse events and dosing protocols are summarised in the linked overviews.

Ketamine Depressive Disorders Adverse events Dose summary Clinical guidelines

CompoundArylcyclohexylamine

Ketamine

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

Full Ketamine profile

IndicationAround 280 million people live with depression worldwide

Depressive Disorders

Depression is the flagship indication for psychedelic and rapid-acting psychiatry, and the place where the field has gone furthest: an approved drug (esketamine), the first Phase 3 win for a classic psychedelic, and several striking trials of psilocybin for major depression. But it is also where the honest caveats bite hardest. The most rigorous recent analyses suggest much of psilocybin’s apparent edge comes from patients knowing they got the drug, and a head-to-head against a standard antidepressant was not significant on its main measure. This is the umbrella page for the depression family; the resistant, general and bipolar forms each have their own.

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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Clinical guidelines

Ketamine clinical practice guidance

Blossom tracks 18 trial-anchored clinical guidelines for ketamine, covering screening, dosing-session facilitation, safety, and integration competencies relevant to depressive disorders research.

18 guidelines|Ketamine protocol family

View Ketamine guidelines

Academic Research

402 papers

Open Accessmeta

Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials

This randomised clinical trial programme included a phase 1 crossover study (n=26) and a phase 2 placebo-controlled trial (n=122) testing oral prolonged-release ketamine for treatment-resistant depression. The oral tablet caused far less dissociation and cardiovascular change than intranasal esketamine, but it did not meet the main depression outcome at day 21, although some short-term symptom improvement was seen after the first dose.

Published: June 24, 2026
Journal: JAMA Network Open
Authors: Walter, M., zu Eulenburg, C., Damyanova, A., Schmid, K., Schwienbacher, I., Papanastasiou, E., Maiboe, K., Arvastson, L., Strote, C., Gehrlach, D., Eriksson, H.

Open Accessindividual

At-Home Telehealth-Supported Subcutaneous Ketamine Therapy in Adults With Moderate to Severe Depression, Anxiety, or PTSD: A Real-World Observational Study of Safety, Feasibility, and Clinical Outcomes in a Large, Heterogeneous Cohort in the United States

This retrospective observational study (n=3,870) examined telehealth-supported at-home subcutaneous ketamine for adults with moderate to severe depression, anxiety or PTSD and found large reductions in symptom scores over six sessions, with most patients reaching a clinically meaningful improvement. Adverse events were uncommon and no serious complications related to the injections were reported.

Published: June 19, 2026
Journal: Journal of Medical Internet Research
Authors: Parks, A. C., Woodward, A. L., Henry, R. D., Arden, K. A., Vando, L., Swain, J., Lamichhane, B.

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.

Paywallindividual

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.

Clinical Trials

322 trials

Not yet recruitingPhase II

Adjunctive Oral KET-AD Capsules in Treatment Resistant Bipolar Depression

This Phase II, randomised, double-blind, placebo-controlled trial (n=160) will assess the safety and tolerability of adjunctive oral KET-AD in adults with treatment-resistant bipolar depression. Participants will receive either KET-AD 140 mg to 280 mg or matching placebo, taken orally 3 times a week for up to 7 weeks alongside standard of care. The study uses a parallel-group design with 1:1 randomisation, stratified by site and current standard of care treatment. The first 3 weeks are a titration phase to identify each participant’s highest tolerated dose, followed by a 4-week maintenance phase at the established dose for those who qualify. Key secondary and exploratory measures include participant- and investigator-reported depression symptoms, pharmacokinetics of KET-AD and its metabolites, and use of an electronic telehealth/app platform for at-home dosing. Safety will be monitored throughout by the study team and a Data Safety Monitoring Board, with follow-up visits planned for Day 50 and Day 64.

Started: October 30, 2026
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT07644767

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 II

Subanesthetic Ketamine Infusions for Depressive Symptoms in Intensive Care Unit Patients

This Phase II randomised, double-blind, placebo-controlled multicentre trial (n=50) will evaluate subanesthetic intravenous ketamine for depressive symptoms in adult intensive care unit patients. Adults aged 18 to 99 years who have been in the ICU for at least 6 days and have moderate-to-severe depressive symptoms (PHQ-9 score of 10 or greater) will be assigned to ketamine or placebo, with the main aim of assessing change in depressive symptoms and safety. Participants will receive either ketamine 0.5 mg/kg, up to 60 mg per infusion, infused intravenously over 40 to 60 minutes once daily for 2 consecutive days, or matching 0.9% sodium chloride placebo given on the same schedule. The trial uses 1:1 allocation, parallel groups, and quadruple masking, with study drug prepared in identical infusion bags. Outcomes include PHQ-9 change from baseline to Day 30 after the last infusion, safety events during and after infusion, and follow-up assessments at Days 1, 7, 14, and 30 post-last infusion; secondary measures include HADS, Clinical Global Impression scales, intensive care unit and hospital length of stay, and mortality.

Started: May 14, 2026
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT07639359

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

Explore further

Search all Ketamine papers Search all Depressive Disorders trials Full Ketamine profile Full Depressive Disorders profile