Indication

Treatment Resistant Depression

84 registered trials testing Psilocybin, Ketamine, DMT for this indication, 22 recruiting now.

Sponsors register this under 5 different names, all collected here: Treatment Resistant Depression · Treatment Resistant Depression (TRD) · Treatment-Resistant Depression · Treatment-resistant Depression · Treatment-resistant Depression (TRD)

Registered trials

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In Phase 3

Substances tested

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Trials

All 84 trials for Treatment Resistant Depression

Trial	Status	Phase	Substance	Sites
Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant DepressionNCT06278779 · The George Institute	Recruiting	Phase 4	ketamine	7
Esketamine With or Without Integration Therapy for Treatment-Resistant DepressionNCT07369102 · University of Puerto Rico	Recruiting	Phase 4	ketamine	2
ECT with Ketamine Anesthesia Vs High Intensity Ketamine with ECT Rescue for Treatment-Resistant DepressionNCT03272698 · University of Saskatchewan	Recruiting	Phase 4	ketamine	1
InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpressionNCT06781697 · Sunnybrook Health Sciences Centre	Recruiting	Phase 3	ketamine	1
Ketamine Augmentation of ECT in Treatment-Resistant DepressionNCT07088380 · Università Vita-Salute San Raffaele	Recruiting	Phase 3	ketamine	1
The Effect of a Six Week Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.NCT05973851 · Dr. Inge Winter	Recruiting	Phase 3	ketamine	12
Evaluating the Role of Psilocybin Monitors in Psilocybin Therapy for Treatment Resistant DepressionNCT07211438 · Centre for Addiction and Mental Health	Recruiting	Phase 2	psilocybin	2
Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)NCT06512220 · Centre for Addiction and Mental Health	Recruiting	Phase 2	psilocybin	1
Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND)NCT06518720 · Centre for Addiction and Mental Health	Recruiting	Phase 2	psilocybin	1
i-CBT and IV Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical TrialNCT06480500 · University Health Network, Toronto	Recruiting	Phase 2	ketamine	1
Psilocybin rTMS for Treatment Resistant DepressionNCT06132178 · University of Texas at Austin	Recruiting	Phase 2	psilocybin	1
Psilocybin Microdosing With Psychotherapy for Treatment-Resistant DepressionNCT07183748 · Beersheva Mental Health Center	Recruiting	Phase 2	psilocybin	1
Intravenous Ketamine for Treatment-Resistant DepressionNCT06668571 · Mayo Clinic	Recruiting	Phase 2	ketamine	1
Psilocybin for Hospitalized Patients with Treatment-resistant DepressionNCT06378229 · University Hospital, Ghent	Recruiting	Phase 2	psilocybin	1
Gamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant DepressionNCT06480201 · Texas A&M University	Recruiting	Phase 1	ketamine	2
Personalized DBS Targeting for Treating DepressionNCT06784388 · Second Affiliated Hospital, Zhejiang University, School of Medicine	Recruiting	Early Phase 1	ketamine	1
Coaching as an Adjunct to Ketamine Therapy for Treatment-Resistant DepressionNCT07563868 · Massachusetts General Hospital	Recruiting	Not applicable	ketamine	2
Working Mechanisms and Effectiveness of IV Ketamine-assisted Psychotherapy on Depression in TRD ClientsNCT07706478 · Senz	Recruiting	N/A	ketamine	1
Belief Updating in Treatment Resistant DepressionNCT05577247 · Assistance Publique - Hôpitaux de Paris	Recruiting	N/A	ketamine	1
Esketamine Nasal Spray in Real-World Settings in Treatment-Resistant DepressionNCT07146503 · Riccardo Guglielmo	Recruiting	N/A	ketamine	5
University of Iowa Interventional Psychiatry Service Patient RegistryNCT04480918 · Mark Niciu	Recruiting	N/A	ketamine	1
IV Ketamine vs. IN Esketamine for MDD TRDNCT06488586 · Gustavo Vazquez	Recruiting	N/A	ketamine	1
Biomarker-Guided Antidepressant SelectionNCT07680140 · Weill Medical College of Cornell University	Not yet recruiting	Phase 4	ketamine	1
Oral Aspirin + Ketamine as Adjunct to Oral Antidepressant Therapy for DepressionNCT05615948 · Theresa Jacob, PhD, MPH	Completed	Phase 4	ketamine	1
Low-dose Ketamine Infusion Among Adolescents With Treatment-resistant DepressionNCT05045378 · Taipei Veterans General Hospital, Taiwan	Completed	Phase 4	ketamine	1
Ketamine for Older Adults PilotNCT04504175 · Washington University School of Medicine	Completed	Phase 4	ketamine	5
Comparing Ketamine and Propofol Anesthesia for Electroconvulsive TherapyNCT01935115 · University of Saskatchewan	Completed	Phase 4	ketamine	1
D-cycloserine for Relapse Prevention Following Intravenous Ketamine in Treatment-resistant DepressionNCT02772211 · Sheba Medical Center	Unknown status	Phase 4	ketamine	1
Ketamine Frequency Treatment for Major Depressive DisorderNCT00646087 · Essentia Health	Withdrawn	Phase 4	ketamine	1
Efficacy, Safety, and Tolerability of COMP360 in Participants With TRDNCT05624268 · COMPASS Pathways	Completed	Phase 3	psilocybin	40
Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRDNCT05711940 · COMPASS Pathways	Active, not recruiting	Phase 3	psilocybin	116
Predictors of Intravenous Ketamine Response in TRDNCT05625555 · Abraham Nunes	Active, not recruiting	Phase 3	ketamine	1
Psilocybin-Assisted Therapy in Treatment-Resistant DepressionNCT06303739 · University of North Carolina, Chapel Hill	Active, not recruiting	Phase 3	psilocybin	1
A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant DepressionNCT02417064 · Janssen Research & Development, LLC	Completed	Phase 3	ketamine	90
A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant DepressionNCT02418585 · Janssen Research & Development, LLC	Completed	Phase 3	ketamine	48
A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant DepressionNCT02497287 · Janssen Research & Development, LLC	Completed	Phase 3	ketamine	109
ELEKT-D: Electroconvulsive Therapy (ECT) vs. Ketamine in Patients With Treatment Resistant Depression (TRD)NCT03113968 · Bo Hu	Completed	Phase 2 / Phase 3	ketamine	5
ECT vs. EsketamineNCT04924257 · Medical University Innsbruck	Withdrawn	Phase 3	ketamine	1
Evaluation of Schemes of Administration of Intravenous Ketamine in DepressionNCT03742557 · National Institute of Neurology and Neurosurgery, Mexico	Unknown status	Phase 3	ketamine	1
Action of Ketamine in Treatment-Resistant DepressionNCT01945047 · University of Ottawa	Completed	Phase 2 / Phase 3	ketamine	1
Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of PsilocybinNCT06341426 · University Health Network, Toronto	Active, not recruiting	Phase 2	psilocybin	2
Psilocybin for Treatment-Resistant DepressionNCT06230757 · University of Colorado, Denver	Completed	Phase 2	psilocybin	1
Does Psilocybin Require Psychedelic Effects to Treat Depression?NCT05710237 · Centre for Addiction and Mental Health	Completed	Phase 2	psilocybin	1
Ketamine-Assisted Psychotherapy for Treatment-Resistant DepressionNCT07247006 · University of Rochester	Not yet recruiting	Phase 2	ketamine	1
Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use DisorderNCT07499583 · Indiana University	Not yet recruiting	Phase 1 / Phase 2	psilocybin	2
The Safety and Efficacy of Psilocybin in Patients With Treatment-resistant Depression and Chronic Suicidal IdeationNCT05220410 · Sheppard Pratt Health System	Completed	Phase 2	psilocybin	1
Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)NCT07210112 · Centre Hospitalier St Anne	Not yet recruiting	Phase 2	psilocybin	1
A Trial of GH001 in Patients With Treatment-resistant DepressionNCT05800860 · GH Research Ireland Limited	Completed	Phase 2	dmt	11
Efficacy and Safety of Psilocybin in Treatment-Resistant Major DepressionNCT04670081 · Central Institute of Mental Health, Mannheim	Completed	Phase 2	psilocybin	2
An Open Label Study of the Safety and Efficacy of Psilocybin in Participants With Treatment-Resistant Depression (P-TRD)NCT04433858 · Sheppard Pratt Health System	Active, not recruiting	Phase 2	psilocybin	2
A Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety and Efficacy of PCN-101 in TRDNCT05414422 · Perception Neuroscience	Completed	Phase 2	ketamine	21
Efficacy of Repeated Ketamine Infusions for Treatment-resistant DepressionNCT02360280 · VA Office of Research and Development	Completed	Phase 2	ketamine	1
The Safety and Efficacy Of Psilocybin as an Adjunctive Therapy in Participants With Treatment Resistant DepressionNCT04739865 · COMPASS Pathways	Completed	Phase 2	psilocybin	2
Clinical Study of GH001 in DepressionNCT04698603 · GH Research Ireland Limited	Completed	Phase 1 / Phase 2	dmt	1
Psilocybin for Treatment-Resistant DepressionNCT05029466 · Brain and Cognition Discovery Foundation	Completed	Phase 2	psilocybin	1
The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant DepressionNCT03775200 · COMPASS Pathways	Completed	Phase 2	psilocybin	25
The Safety and Efficacy of Psilocybin in Participants With Type 2 Bipolar Disorder (BP-II) Depression.NCT04433845 · Sheppard Pratt Health System	Unknown status	Phase 2	psilocybin	1
Psilocybin Versus Ketamine in Treatment-Resistant DepressionNCT05383313 · National Institute of Mental Health, Czech Republic	Unknown status	Phase 2	psilocybin, ketamine	1
Low Dose Intravenous Ketamine in Treatment Resistant Depression PatientsNCT02935595 · The University of Texas Health Science Center, Houston	Completed	Phase 2	ketamine	1
Psilocybin in Depression Resistant to Standard TreatmentsNCT04959253 · King's College London	Unknown status	Phase 2	psilocybin	1
The UTHealth Ketamine ProjectNCT02882711 · The University of Texas Health Science Center, Houston	Terminated	Phase 2	ketamine	1
Effect of Lithium Versus Placebo in Adults With Treatment-Resistant Depression Who Are Receiving KetamineNCT03290963 · William V. Bobo, M.D.	Withdrawn	Phase 2	ketamine	1
Double-Blind, Placebo-Controlled Trial of Ketamine Therapy in Treatment-Resistant Depression (TRD)NCT01920555 · Massachusetts General Hospital	Completed	Phase 2	ketamine	6
Efficacy and Safety of TAK-653 in Treatment-Resistant DepressionNCT03312894 · Millennium Pharmaceuticals, Inc.	Withdrawn	Phase 2	ketamine	—
Ketamine for Treatment-resistant Depression: A Multicentric Clinical Trial in Mexican PopulationNCT01868802 · Paul J. Lamothe	Unknown status	Phase 2	ketamine	1
Optimization of IV Ketamine for Treatment Resistant DepressionNCT00768430 · Baylor College of Medicine	Completed	Phase 2	ketamine	2
Psilocybin for Treatment-Resistant Depression in AutismNCT06731621 · Centre for Addiction and Mental Health	Active, not recruiting	Phase 1	psilocybin	1
KET-RO Plus RO DBT for Treatment Resistant DepressionNCT06138691 · Washington University School of Medicine	Completed	Phase 1	ketamine	1
Ketamine Biomarker ValidationNCT07307768 · Soterix Medical	Not yet recruiting	Phase 1	ketamine	1
Ketamine Associated ACC GABA and Glutamate Change and Depression Remission:NCT03573349 · Mayo Clinic	Active, not recruiting	Early Phase 1	ketamine	1
Psilocybin-Assisted Group Integration Psychotherapy for Treatment-Resistant DepressionNCT07737990 · Joshua Rosenblat	Enrolling by invitation	Not applicable	psilocybin	1
2-Year Study of Vagus Nerve Stimulation for Higher-Grade Treatment-Resistant Depression: Clinical Outcomes and Policy RecommendationNCT07097025 · Dr.Yoav Domany	Completed	N/A	ketamine	2
Role Of Ketamine in Treatment-Resistant Major Depressive Disorder And Its Effect on SuicidalityNCT04101474 · Assiut University	Completed	Not applicable	ketamine	1
Effect of Ketamine on Neurological Activity as Measured by Electroencephalogram (EEG)NCT05095792 · Entheon Biomedical Corp.	Terminated	N/A	ketamine	1
Observation of Safety and Tolerability Within 1 Year of the Use of R-ketamine / Placebo in Drug-resistant DepressionNCT06232291 · Medical University of Gdansk	Completed	N/A	ketamine	1
Glutamate Emotion Memory StudyNCT05809609 · University of Oxford	Unknown status	Not applicable	ketamine	1
Auditory MMN EEG in TRD in Response to KetamineNCT05464264 · Unity Health Toronto	Unknown status	N/A	ketamine	1
A Naturalistic Study of Ketamine for Treatment Resistant Mood DisordersNCT04226963 · Medical University of Gdansk	Completed	N/A	ketamine	1
Reward Emotion Learning and Ketamine StudyNCT04850911 · University of Oxford	Unknown status	Not applicable	ketamine	1
Long Term Follow Up Study to COMP 001 And COMP 003 Trials (P-TRD LTFU)NCT04519957 · COMPASS Pathways	Completed	N/A	psilocybin	8
Pharmacogenetics Associated With IV KetamineNCT04695405 · Brain and Cognition Discovery Foundation	Completed	N/A	ketamine	1
Intranasal Esketamine to Maintain the Antidepressant Response to IV Racemic KetamineNCT04856124 · Psych Atlanta	Completed	N/A	ketamine	1
Neurocognitive Features of Patients With Treatment-Resistant DepressionNCT03134066 · Massachusetts General Hospital	Completed	N/A	ketamine	—
Administration of Subanesthetic Dose of Ketamine and Electroconvulsive Treatment for Treatment Resistant DepressionNCT02522377 · The Cleveland Clinic	Completed	Not applicable	ketamine	1

Records from ClinicalTrials.gov API v2, data build 2026-08-25. Indications are the sponsors’ own words. LSD.com reports registered clinical research. It is not medical advice, it is not a recommendation to take any substance, and trial listings are not endorsements. Talk to a clinician.