Major depressive disorder drug pipeline
- MeSH D003865
Subtypes: Postpartum depression, Treatment-resistant depression
40 compounds from 31 companies are in active clinical development for major depressive disorder, including 9 at Phase 3 or beyond.
- Approved 1
- Phase 3 8
- Phase 2/3 2
- Phase 2 18
- Phase 1/2 1
- Phase 1 2
- Unknown 1
- Discontinued 7
Mechanisms: Small molecule (34) · Psychedelic (5) · Neuroactive Steroid (1)
Pipeline data compiled July 2026 · every fact sourced.
Upcoming readouts & recent results
Phase 2 COMP360 recurrent-MDD topline anticipated (estimated primary completion Sep 2025); no results reported yet. ↗
Sertraline-controlled Phase 3 MDD topline anticipated; primary-completion estimate 30 Jun 2026. ↗
ClinicalTrials.gov estimated primary completion (and estimated study completion) of the confirmatory Phase 2b/3 study NCT06254612: 15 July 2026. ↗
AMPLIFY Phase 2 topline (adjunctive MDD): HAMD-17 change at Week 6 vs. placebo, expected Q3 2026. ↗
Confirmatory Phase 3 MDD3003 anticipated; primary completion estimated end of 2026. ↗
Topline data anticipated from the Phase 3 adjunctive MDD study of milsaperidone (Bysanti). ↗
Phase 3 APPROACH topline data expected in Q4 2026. ↗
Topline results from the confirmatory Phase 2b/3 study SP-624-202 of forvisirvat 20 mg once daily vs placebo over 4 weeks in MDD (456 randomised; primary efficacy endpoint pre-specified in females), anticipated later in 2026. ↗
ClinicalTrials.gov estimated primary completion of AERON-1, the US Phase 2 adjunctive study of DT-101 in MDD (primary endpoint: change from baseline in MADRS total score at Day 56): May 2027. ↗
Anticipated Phase 2 topline (MADRS change from baseline at week 6) for icalcaprant in major depressive disorder ↗
Topline results from Tarian-1, the global Phase 2 monotherapy study of DT-101 in major depressive disorder (primary endpoint: change from baseline in MADRS total score at Day 42), anticipated in the second half of 2027. ↗
Phase 2 HORIZON topline (MADRS change at Week 6) in MDD anticipated following an estimated February 2028 primary completion.
Phase 2 apimostinel +/- ASAT in MDD: primary completion anticipated 2029 ↗
CLARITY Phase 3 (MDD with EDS) topline anticipated after a ~December 2028 primary completion. ↗
LB Pharmaceuticals plans to initiate a Phase 2 adjunctive-MDD trial of LB-102 in early 2027, with topline data expected in 1H 2029. ↗
- No guidance — study completed 26 Nov 2025, topline undisclosedAnticipatedENX-104Topline dataNCT07253324
Topline from the Phase 1 multiple-ascending-dose study of ENX-104 in 48 patients with major depressive disorder with anhedonia (NCT07253324) — safety, tolerability, PK and pharmacodynamics, the first data in the target population. Completed 26 November 2025; nothing disclosed. ↗
- No guidance — study completed 2 Sep 2025, results undisclosedAnticipatedENX-104Full resultsNCT07253272
D2/D3 receptor occupancy results from the Phase 1 PET study of single-dose ENX-104 in 10 healthy volunteers (NCT07253272) — the dose-to-occupancy relationship that would anchor Phase 2 dose selection against the intended 10-50% occupancy window. Completed 2 September 2025; nothing disclosed. ↗
Phase 2b (NCT06836063) topline in major depressive disorder: ropanicant 45 mg twice daily met the primary endpoint, change from baseline in MADRS total score at Week 6, with an ML-estimated mean difference versus placebo of -3.572 in the Full Analysis Set (p = 0.038); no result was disclosed for the 30 mg twice-daily arm. ↗
KOASTAL-2 and KOASTAL-3 both missed; Neumora discontinued navacaprant for MDD. ↗
First-in-human single-ascending-dose results for ENX-104 presented at ASCP 2026: safe and well tolerated at all 5 dose levels with no serious or severe adverse events, dose-proportional plasma exposure, sustained central target engagement (dose-related decreases in adaptive tracking lasting >=48 h) and prolactin-confirmed peripheral D2/D3 antagonism. ↗
FDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults. ↗
Compounds in development (40)
Also in development for subtypes of Major depressive disorder
- LPCN 1154 (oral brexanolone)Phase 3Lipocine Inc.for Postpartum depression
- Luvesilocin (RE104)Phase 2Reunion Neuroscience Inc.for Postpartum depression
- Mebufotenin (inhaled 5-MeO-DMT, GH001)Phase 2GH Research PLCfor Postpartum depression
- Psilocybin (COMP360)Phase 3COMPASS Pathways plcfor Treatment-resistant depression
- ALTO-207Phase 2Alto Neuroscience, Inc.for Treatment-resistant depression
- BPL-003 (intranasal 5-MeO-DMT benzoate)Phase 2Atai Beckley N.V. (AtaiBeckley)for Treatment-resistant depression
- Mebufotenin (inhaled 5-MeO-DMT, GH001)Phase 2GH Research PLCfor Treatment-resistant depression
- VLS-01Phase 2Atai Beckley N.V. (AtaiBeckley)for Treatment-resistant depression
- Mefluleucine (NV-5138)DiscontinuedSupernus Pharmaceuticals, Inc.for Treatment-resistant depression
- MK-1942DiscontinuedMerck & Co., Inc.for Treatment-resistant depression
- TS-161DiscontinuedOOTEMON Co., Ltd.for Treatment-resistant depression
Trials recruiting now (198)
198 drug-interventional major depressive disorder trials recruiting now, of 1,650 registered interventional trials. Browse all on ClinicalTrials.gov →
Celecoxib, Minocycline
Kurvelo, Placebo COC
bupropion hydrobromide, Placebo
- Phase 4Understanding the Role of the Kappa Opioid Receptor in Ketamine's Attenuation of Suicidal Thoughts
Ketamine hydrochloride infusion
Daridorexant 50 mg, Placebo
Vortioxetine, Cariprazine (Augmentation Phase)
Hyperbolic tapering, Linear tapering
Psychopharmacological treatment
Lumateperone 42 mg
Semaglutide Injectable Product, Placebo
Valbenazine
- Phase 4Disposition Kinetics of Dolutegravir Among People Living With HIV With Major Depression in Nigeria
Fluoxetine
Showing the 12 most advanced of 198 recruiting drug trials · see all on ClinicalTrials.gov →
Frequently asked
- How many drugs are in development for major depressive disorder?
- 40 compounds from 31 companies are in active clinical development for major depressive disorder, including 9 at Phase 3 or beyond.
- Which major depressive disorder drugs are in Phase 3?
- Phase 3 (or later) programs for major depressive disorder include Lumateperone (ITI-007), Ammoxetine (S-071031B), Azetukalner (XEN1101), CYB003 (deupsilocin), Lysergide D-tartrate (MM120 / LSD), Milsaperidone (VHX-896), Osavampator (NBI-1065845), Seltorexant (JNJ-42847922) and Solriamfetol (Sunosi).
- What are the next major depressive disorder trial readouts?
- Upcoming catalysts include Psilocybin (COMP360) (September 2025), Ammoxetine (S-071031B) (1H 2026), Forvisirvat (July 2026) and Elunetirom (ABX-002) (Q3 2026).
- How many clinical trials are recruiting for major depressive disorder?
- 198 drug-interventional major depressive disorder trials are currently recruiting participants, out of 1,650 registered interventional trials.