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Disease

Major depressive disorder

Late-stage therapeutic development
Also known as MDD, major depression, major depressive disorder and accelerated response to antidepressant drug treatment, major depressive disorder, response to citalopram therapy in+6 more

MDD, major depression, major depressive disorder and accelerated response to antidepressant drug treatment, major depressive disorder, response to citalopram therapy in, recurrent major depression, single major depressive episode, unipolar depression, unipolar depression, susceptibility to, major depressive disorder 1, major depressive disorder 2.

24
Clinical trials
12
Associated genes
12
Related proteins
Current focus
5-hydroxytryptamine 2a biologyD(2) dopamine biologyTherapeutic development
Latest activity
beta

Recent clinical, regulatory, research and industry developments relating to this disease.

A Phase 2a Study to Evaluate the Safety and Tolerability of Two Repeated Doses of GM-2505 at a 2-Week Interval in Patients With Major Depressive Disorder.

Clinical trial2026-10-19Status changed to Completed · ClinicalTrials.gov

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder

Clinical trial2026-10-13Status changed to Active, not recruiting · ClinicalTrials.gov

Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder

Clinical trial2026-10-09Status changed to Completed · ClinicalTrials.gov

Integrated Internet-Based Cognitive Behavioural Therapy (i-CBT) and Intravenous Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical Trial

Clinical trial2026-10-06Status changed to Active, not recruiting · ClinicalTrials.gov

Long-term Study to Assess the Safety and Effectiveness of NMRA-335140 in Participants With Major Depressive Disorder

Clinical trial2026-09-14Status changed to Terminated · ClinicalTrials.gov

A Multi-centre, Double-blind Randomised Controlled Trial to Compare Mirtazapine Versus Placebo Over 12 Weeks in Patients With Multimorbid Major Depression and Inflammatory Bowel Disease (MD-IBD): a Feasibility Study

Clinical trial2026-08-19Status changed to Completed · ClinicalTrials.gov

A Multi-center, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of SP-624 in the Treatment of Adults With Major Depressive Disorder

Clinical trial2026-08-18Status changed to Completed · ClinicalTrials.gov

A Phase III, Placebo-Controlled, Randomized, Double-Blind Trial of Oral Doses of CYB003 to Assess Combined Safety and Efficacy in Humans With Major Depressive Disorder

Clinical trial2026-08-12Status changed to Active, not recruiting · ClinicalTrials.gov

Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)

Clinical trial2026-08-11Status changed to Active, not recruiting · ClinicalTrials.gov

Lemborexant for the Treatment of Residual Insomnia in Adequately Treated Major Depressive Disorder: A Pilot Randomized Controlled Trial

Clinical trial2026-07-30Status changed to Terminated · ClinicalTrials.gov

An Open-Label, Randomized Controlled Trial of Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disorder (MND) in Persons With HIV

Clinical trial2026-07-14Status changed to Suspended · ClinicalTrials.gov

What's happening now

An analyst briefing on current research, clinical, regulatory and industry activity surrounding this disease.

Executive briefingUpdating summary…Momentum: Moderate
Key developments
  • 6 clinical trials expected to report results, the earliest in Q3 2028.
  • 10 industry developments reported.
Upcoming Milestones
Clinical Milestones15View all 15
Results expected 5
Recently completed 5
Other updates 3
+7 more in the activity timeline below
Industry & Market10View all 10
+5 more in the activity timeline below
Activity timeline25

Therapeutic landscape

Therapies with a regulatory footing for this condition, alongside the wider set of agents co-studied with it in the literature.

Approved & established therapies
Esketamine hydrochlorideapproved

Original application approval — Spravato, in combination with a SSRI or SNRI, is indicated for adults with treatment-resi… (2019)

Duloxetineapproved

Generic approval — Treatment of major depressive disorder Treatment of diabetic peripheral neuropathic pain… (2015)

Clinical trials

15 sponsors · 6 new · 6 completed in the last 12 months (net +5)

The current development programme across all trial phases.

Clinical programme
24
All trials
6
Active
18
Late-stage
6
Completed
Late-stage studies

A Double-blind, Randomized, Psychoactive Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine 84 mg in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder in Adolescent Participants With Acute Suicidal Ideation or Behavior

Phase 3 · Recruiting · Janssen Research & Development, LLC

RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)

Phase 4 · Recruiting · Mayo Clinic

Prefrontal Glutamatergic Modulation by N-acetylcysteine and Mindfulness-based Cognitive Therapy for Mild Depression in Youth

Phase 3 · Recruiting · University of Cincinnati

A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Study of Solriamfetol in Subjects With Major Depressive Disorder With Excessive Daytime Sleepiness Symptoms

Phase 3 · Recruiting · Axsome Therapeutics, Inc.

Sequential Multiple Assignment Randomized Trial for Bipolar Depression

Phase 4 · Active, not recruiting · Massachusetts General Hospital

A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate Efficacy and Safety of Seltorexant as Monotherapy in Adult and Elderly Participants With Major Depressive Disorder (MDD) and an Open-label Long-term Extension Treatment With Seltorexant

Phase 3 · Recruiting · Janssen Research & Development, LLC
Recruiting

A Double-blind, Randomized, Psychoactive Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine 84 mg in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder in Adolescent Participants With Acute Suicidal Ideation or Behavior

Phase 3 · Recruiting · Janssen Research & Development, LLC

RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)

Phase 4 · Recruiting · Mayo Clinic

Prefrontal Glutamatergic Modulation by N-acetylcysteine and Mindfulness-based Cognitive Therapy for Mild Depression in Youth

Phase 3 · Recruiting · University of Cincinnati

A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Study of Solriamfetol in Subjects With Major Depressive Disorder With Excessive Daytime Sleepiness Symptoms

Phase 3 · Recruiting · Axsome Therapeutics, Inc.

A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate Efficacy and Safety of Seltorexant as Monotherapy in Adult and Elderly Participants With Major Depressive Disorder (MDD) and an Open-label Long-term Extension Treatment With Seltorexant

Phase 3 · Recruiting · Janssen Research & Development, LLC
Recently completed

An Interventional, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy and Safety of Esketamine Nasal Spray in Korean Participants With Treatment-Resistant Depression(TRD)

Phase 4 · Completed · Janssen Korea, Ltd., Korea

Clonidine to Prevent Postictal Delirium After ElectroConvulsive Therapy: a Randomised, Placebo-controlled, Triple-blind, Single-centre Trial.

Phase 4 · Completed · Insel Gruppe AG, University Hospital Bern

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder

Phase 3 · Completed · Neumora Therapeutics, Inc.

Efficacy of Bacillus Coagulans in Alleviating Anxiety and Depression in Patients With Functional Dyspepsia：A Prospective, Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Phase 4 · Completed · Xijing Hospital of Digestive Diseases

A Randomized, Blinded, Placebo-Controlled Study to Evaluate the Saftey and Efficacy of Oral LPCN 1154A in Women With Postpartum Depression

Phase 3 · Completed · Lipocine Inc.

A Phase III, Multicentre, Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, and Tolerability of COMP360 in Participants With Treatment-resistant Depression

Phase 3 · Completed · COMPASS Pathways

Regulatory timeline

Drug regulatory events matched to this condition by indication — EMA.

Product approvals and authorisations
2019emaOriginal application approval — Esketamine hydrochloride· Spravato, in combination with a SSRI or SNRI, is indicated for adults with treatment-resistant Major Depressive Disorder, who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode. source ↗
2015emaGeneric approval — Duloxetine· Treatment of major depressive disorder Treatment of diabetic peripheral neuropathic pain Treatment of generalised anxiety disorder Duloxetine Viatris is indicated in adults source ↗
2014emaOriginal application approval — Duloxetine· Duloxetine Lilly is indicated in adults for: Treatment of major depressive disorder Treatment of diabetic peripheral neuropathic pain Treatment of generalised anxiety disorder Duloxetine Lilly is indicated in adults. source ↗
2004emaOriginal application approval — Duloxetine· Treatment of major depressive disorder. Treatment of diabetic peripheral neuropathic pain. Treatment of generalised anxiety disorder. Cymbalta is indicated in adults. source ↗

European Medicines Agency (CC BY 4.0). Events are matched to this condition by drug indication text — approvals/updates for drugs indicated for it, not disease-specific acts.

Associated genes

12 matches

Genes associated with this disease in the canonical knowledge graph (Open Targets evidence). Number shows the association score.

DRD20.74HTR2A0.70GABRA10.67GRIN2A0.66SLC6A40.64HTR1A0.63SLC6A30.63SLC6A20.62GABRB10.62SCN11A0.62GABRA60.61DRD30.61

Disease biology

12 matches

Proteins whose encoding gene is associated with this disease, reached through the canonical gene→disease graph. Number shows the gene's association score.

D(2) dopamine receptorvia DRD20.745-hydroxytryptamine receptor 2Avia HTR2A0.70Gamma-aminobutyric acid receptor subunit alpha-1via GABRA10.67Glutamate receptor ionotropic, NMDA 2Avia GRIN2A0.66Sodium-dependent serotonin transportervia SLC6A40.645-hydroxytryptamine receptor 1Avia HTR1A0.63Sodium-dependent dopamine transportervia SLC6A30.63Sodium-dependent noradrenaline transportervia SLC6A20.62Gamma-aminobutyric acid receptor subunit beta-1via GABRB10.62Sodium channel protein type 11 subunit alphavia SCN11A0.62Gamma-aminobutyric acid receptor subunit alpha-6via GABRA60.61D(3) dopamine receptorvia DRD30.61

Reference

Authoritative identity, definition & identifiers.

Synonyms

MDD, major depression, major depressive disorder and accelerated response to antidepressant drug treatment, major depressive disorder, response to citalopram therapy in, recurrent major depression, single major depressive episode, unipolar depression, unipolar depression, susceptibility to, major depressive disorder 1, major depressive disorder 2

References & data sources
  • Disease identity & definition — NLM Medical Subject Headings (MeSH), public domain
  • Clinical trials — ClinicalTrials.gov (U.S. National Library of Medicine)
  • Related entities are derived from literature co-mention (studied together) — associative, not causal.