For patients living with depression, clinical trials can be opportunities for successful treatment when traditional treatments yield no results. Depression is a multifaceted and persistent condition, with many patients reporting limited relief even after trying multiple therapies. By considering clinical trials, clinicians can connect patients with emerging therapies, novel treatments, and targeted approaches not yet widely available. 

The following are a selection of phase 3 clinical trials related to depression that are currently recruiting in the United States.

Overview of Phase 3 Clinical Trials Focused on Depression
Study TitlePhaseEstimated EnrollmentStudy StartEstimated Completion
A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)3450July 2025July 2027
A Study to Assess the Safety and Efficacy of Oral LPCN 1154A in Women With Severe PPD380June 2025May 2026
Long-term Study to Assess the Safety and Tolerability of NBI-1065845 as an Adjunctive Treatment in Participants with Major Depressive Disorder (MDD)3600April 2025May 2030
A Phase 3 Trial of MM120 for Major Depressive Disorder (EMERGE)3140April 2025May 2027
Evaluation of Efficacy and Safety of Milsaperidone as Adjunctive Therapy in Patients with Major Depressive Disorder3500March 2025March 2028
Nebulized Ketamine for the Treatment of Major Depressive Disorder in an Inpatient Setting340October 2024September 2026
Phase 3 Study of Adjunctive Treatment with Seltrorexant in Adult and Elderly Participants with Major Depressive Disorder and Insomnia Symptoms3752July 2024November 2027
Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients3384May 2024May 2027
Depression-related Phase 3 Clinical Trials Rundown

A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)

  • Sponsor: Xenon Pharmaceuticals Inc.
  • Goal: To evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD).
  • Intervention: Azetukalner, Placebo
  • Primary Outcome Measure: Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at week 6
  • Timeframe: Baseline to 6 weeks
  • Study Details
  • Source

A Study to Assess the Safety and Efficacy of Oral LPCN 1154A in Women With Severe PPD

  • Sponsor: Lipocine Inc.
  • Goal: To test the study drug, LPCN 1154A, as a possible treatment for postpartum depression (PPD).
    Intervention: LPCN 1154A, Placebo
  • Primary Outcome Measure: Change from baseline in HAM-D17 total score compared to placebo.
  • Timeframe: Baseline to hour 60
  • Study Details
  • Source

Long-Term Study to Assess the Safety and Tolerability of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)

  • Sponsor: Neurocrine Biosciences
  • Goal: This study will evaluate the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in participants with MDD.
  • Intervention: NBI-1065845
  • Primary Outcome Measure: Number of participants with treatment-emergent adverse events (TEAEs).
    Timeframe:     Baseline through week 52
  • Study Details
  • Source

A Phase 3 Trial of MM120 for Major Depressive Disorder (Emerge)

  • Sponsor: Mind Medicine, Inc.
  • Goal: The study consists of a 12-week randomized, double-blind, single-dose administration period evaluating MM120 versus placebo, followed by a 40-week extension phase with the opportunity for open-label treatment. During this phase, participants will be monitored and evaluated for potential treatment with MM120 based on pre-specified safety and symptom severity criteria.
    Intervention: MM120 (LSD D-Tartrate), Placebo
  • Primary Outcome Measure: Change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6.
  • Timeframe: Baseline to week 6
  • Study Details
  • Source

Evaluation of Efficacy and Safety of Milsaperidone as Adjunctive Therapy in Patients with Major Depressive Disorder

  • Sponsor: Vanda Pharmaceuticals
  • Goal: To determine the efficacy and safety of milsaperidone compared to placebo as adjunctive therapy in patients with Major Depressive Disorder.
  • Intervention: Milsaperidone, Placebo
  • Primary Outcome Measure: Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
  • Timeframe: 6 weeks
  • Study Details
  • Source

Nebulized Ketamine for the Treatment of Major Depressive Disorder in an Inpatient Setting

  • Sponsor: Theresa Jacob, PhD, MPH
  • Goal: The purpose of this study is to assess if nebulized ketamine can reduce depressive symptoms.
  • Intervention: Nebulized Ketamine
  • Primary Outcome Measure: Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS).
  • Timeframe: 8-10 days
  • Study Details
  • Source

Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms

  • Sponsor: Janssen Research & Development, LLC
  • Goal: The purpose of this study is to know how well seltorexant works, and also to evaluate safety and maintenance effect of seltorexant compared with placebo as an adjunctive therapy to an antidepressant in improving depressive symptoms in participants with major depressive disorder with insomnia symptoms (MDDIS) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
  • Intervention: Seltorexant, SSRI/SNRI, Placebo
    Primary Outcome Measure:     Part 1: Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at day 43; Part 2: Time from randomization to the first relapse in participants who achieve a stable response.
  • Timeframe: Baseline, Day 43; Time from randomization to the first relapse during the maintenance phase (up to 2 years and 10 months)
  • Study Details
  • Source

Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients

  • Sponsor: Intra-Cellular Therapies, Inc.
  • Goal: This is a multicenter, randomized, double-blind, placebo-controlled study in pediatric patients who are experiencing major depressive episodes (MDEs) associated with a primary diagnosis of bipolar I or bipolar II disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5).
  • Intervention: Lumateperone, Placebo
  • Primary Outcome Measure: Children's Depression Rating Scale-Revised (CDRS-R)
  • Timeframe: Week 6
  • Study Details
  • Source
Related Guidelines Include:

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