Which treatment-resistant depression drugs are in Phase 3?

Phase 3 (or later) programs for treatment-resistant depression include Psilocybin (COMP360).

What are the next treatment-resistant depression trial readouts?

Upcoming catalysts include TS-161 (2025-06-10), Psilocybin (COMP360) (fourth quarter 2026) and ALTO-207 (2H 2027).

How many clinical trials are recruiting for treatment-resistant depression?

33 drug-interventional treatment-resistant depression trials are currently recruiting participants, out of 156 registered interventional trials.

Mood Disorders

Treatment-resistant depression drug pipeline

MeSH D061218
Subtype of Major depressive disorder

8 compounds from 7 companies are in active clinical development for treatment-resistant depression, including 1 at Phase 3 or beyond.

8Compounds

7Companies

1Phase 3+

3Upcoming readouts

35Trials recruiting

Phase 3 1
Phase 2 4
Discontinued 3

Mechanisms: Psychedelic (4) · Small molecule (4)

Pipeline data compiled July 2026 · every fact sourced.

Upcoming readouts & recent results

2025-06-10AnticipatedTS-161Full results
fourth quarter 2026AnticipatedPsilocybin (COMP360)Regulatory
Full NDA submission targeted (FDA rolling review underway). ↗
2H 2027AnticipatedALTO-207Topline dataNCT07553637
ALTO-207 Phase 2b TRD topline (MADRS) ↗
2026-02-17ReportedPsilocybin (COMP360)Topline datametNCT05711940
COMP006 met its primary endpoint: -3.8 MADRS (two 25mg doses vs 1mg) at Week 6 (p<0.001). ↗
2025-06-23ReportedPsilocybin (COMP360)Topline datametNCT05624268
COMP005 met its primary endpoint: -3.6 MADRS vs placebo at Week 6 (p<0.001). ↗

See the full catalyst calendar →

Compounds in development (8)

Compound	Company	Phase	Status	Mechanism
Psilocybin (COMP360)BTDRolling ReviewCNPVILAP	COMPASS Pathways plc	Phase 3	Active	5-HT2A Partial agonist
ALTO-207	Alto Neuroscience, Inc.	Phase 2	Recruiting	D3 Agonist
BPL-003 (intranasal 5-MeO-DMT benzoate)BTD	Atai Beckley N.V. (AtaiBeckley)	Phase 2	Active	5-HT1A Agonist
Mebufotenin (inhaled 5-MeO-DMT, GH001)	GH Research PLC	Phase 2	Active	5-HT2A Agonist
VLS-01	Atai Beckley N.V. (AtaiBeckley)	Phase 2	Recruiting	5-HT2A Agonist
Mefluleucine (NV-5138)	Supernus Pharmaceuticals, Inc.	Discontinued	Discontinued	mTORC1 Activator
MK-1942	Merck & Co., Inc.	Discontinued	Discontinued	mGluR2 NAM
TS-161	OOTEMON Co., Ltd.	Discontinued	Discontinued	mGlu2 Antagonist

Trials recruiting now (33)

33 drug-interventional treatment-resistant depression trials recruiting now, of 156 registered interventional trials. Browse all on ClinicalTrials.gov →

Phase 4Esketamine With or Without Integration Therapy for Treatment-Resistant Depression
Esketamine hydrochloride (intranasal)
University of Puerto Ricon=20Puerto Rico · 2 sitesStarted Feb 2026NCT07369102
Phase 4A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression
Esketamine 56 mg, Esketamine 84 mg
Janssen Korea, Ltd., Korean=47South Korea · 6 sitesStarted Jun 2025NCT07053345
Phase 4Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression
Esketamine group, Racemic ketamine
The George Instituten=162Australia · 7 sitesStarted Jun 2024NCT06278779
Phase 4ECT with Ketamine Anesthesia Vs High Intensity Ketamine with ECT Rescue for Treatment-Resistant Depression
Ketamine
University of Saskatchewann=62Canada · 1 siteStarted Sep 2017NCT03272698
Phase 3Lumateperone for Late-Life Depression
Lumateperone, Placebo
Eric Lenzen=100United States · 2 sitesStarted Jun 2026NCT07623135
Phase 3InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression
Ketamine
Sunnybrook Health Sciences Centren=31Canada · 1 siteStarted May 2026NCT06781697
Phase 3Sustained Mood Improvement With Laughing Gas Exposure
Inhalation of Nitrous oxide (Laughing gas) + intravenous saline, inhalation of %100 oxygen + intravenous midazolam
Women's College Hospitaln=120Canada · 5 sitesStarted Feb 2026NCT07262008
Phase 3Ketamine Augmentation of ECT in Treatment-Resistant Depression
Ketamine Hydrochloride, Placebo
Università Vita-Salute San Raffaelen=30Italy · 1 siteStarted Jul 2025NCT07088380
Phase 3The 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.
Esketamine Nasal Product, Ketamine Hydrochloride, Esketamine hydrochloride, Second-line Antidepressants
Dr. Inge Wintern=418Austria, Germany +4 · 12 sitesStarted Aug 2024NCT05973851
Phase 2/3A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial
NRX-101, Oral Placebo
NeuroRx, Inc.n=400United States · 3 sitesStarted Sep 2026NCT07227103
Phase 2Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression
Ketamine hydrochloride injection
University of Rochestern=25United States · 1 siteStarted Jun 2026NCT07247006
Phase 2A Randomized, Double-blind, Placebo-controlled Trial of ALTO-207 in Adults With Treatment-resistant Depression
ALTO-207, Placebo
Alto Neuroscience, Inc.n=178United Kingdom, United States · 48 sitesStarted May 2026Tracked: ALTO-207 NCT07553637

Showing the 12 most advanced of 33 recruiting drug trials · see all on ClinicalTrials.gov →

Frequently asked

How many drugs are in development for treatment-resistant depression?: 8 compounds from 7 companies are in active clinical development for treatment-resistant depression, including 1 at Phase 3 or beyond.
Which treatment-resistant depression drugs are in Phase 3?: Phase 3 (or later) programs for treatment-resistant depression include Psilocybin (COMP360).
What are the next treatment-resistant depression trial readouts?: Upcoming catalysts include TS-161 (2025-06-10), Psilocybin (COMP360) (fourth quarter 2026) and ALTO-207 (2H 2027).
How many clinical trials are recruiting for treatment-resistant depression?: 33 drug-interventional treatment-resistant depression trials are currently recruiting participants, out of 156 registered interventional trials.