Seltorexant (JNJ-42847922) as monotherapy for adults and older adults with major depressive disorder

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 Interventional Janssen Research & Development, LLC · NCT07573176

This trial will test whether seltorexant works better than a placebo to reduce depressive symptoms in adults and elderly people with major depressive disorder.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years to 74 Years
SexAll
SponsorJanssen Research & Development, LLC Industry-sponsored
Locations5 sites (Doral, Florida and 4 other locations)
Trial IDNCT07573176 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, double-blind trial compares seltorexant (JNJ-42847922) with placebo as a monotherapy for adults and elderly participants diagnosed with major depressive disorder. Participants may enter either medication-free or after a washout of up to two recent antidepressants, and must have a current depressive episode of at least two weeks. After the double-blind treatment phase, participants may enter an open-label phase to collect longer-term safety and tolerability data. The trial is conducted at outpatient clinical research sites with regular in-person visits for symptom rating and safety monitoring.

Who should consider this trial

Good fit: Adults and elderly patients who meet DSM-5 criteria for major depressive disorder, have a current episode lasting at least two weeks, have had at least one prior MDD episode, and either are not currently on antidepressants or can be washed out per the protocol (BMI 18–40 kg/m²).

Not a fit: Patients with psychotic features, unstable medical conditions, those who cannot stop disallowed medications or meet the BMI limits, or those with conditions excluded by the protocol may not receive benefit from participation.

Why it matters

Potential benefit: If successful, seltorexant could offer a new monotherapy option that reduces depressive symptoms and may have a tolerability profile distinct from existing antidepressants.

How similar studies have performed: This orexin-2 receptor antagonist approach is relatively new; early-phase trials of seltorexant and related compounds have shown some promising signals but limited large-scale confirmation to date.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion criteria:

* Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features based upon clinical assessment
* Experienced at least one MDD episode prior to their current episode
* Current episode of MDD must be a minimum of 2 weeks in duration
* Must meet one of the following criteria regarding current medication status.

  1. Can be presenting for a new episode of MDD on no antidepressant treatment; however, must have been treated with an antidepressant medication in a prior episode for a minimum of 6 weeks at a stable dose at or above the minimum therapeutic level (medical record/source document).

     OR
  2. Have taken up to two antidepressant treatments started in the current episode that were stopped (withdrawn), or will be withdrawn (washed out) due to inadequate response or intolerance.
* Body Mass Index (BMI) between 18 and 40 kilograms per square meter (kg/m\^2)
* Must be medically stable on the basis of the following performed at screening and double-blind (DB) baseline: physical examination (including a brief neurological examination), vital signs (including blood pressure), and 12-lead electrocardiogram (ECG)

Exclusion criteria:

* Use of ketamine/esketamine in the current depressive episode (up to 2 doses are allowed prior to screening)
* Has treatment-resistant depression (TRD)
* Has a primary DSM-5 diagnosis of panic disorder, generalized anxiety disorder, social anxiety disorder, or specific phobia which has been the primary focus of psychiatric treatment within the past 2 years
* Current active DSM-5 diagnosis of obsessive-compulsive disorder, posttraumatic stress disorder, anorexia nervosa, bulimia nervosa, or fibromyalgia
* Has a history or current diagnosis of a psychotic disorder, bipolar disorder, autism spectrum disorder, borderline personality disorder, or somatoform disorders
* Has dementia, any dementing disease, intellectual disability, or neurocognitive disorder
* Has a current or recent history of homicidal ideation or serious suicidal ideation within the past 3 months or a history of suicidal behavior within the past 6 months
* Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months
* Has any significant sleep disorder, including but not limited to untreated/uncontrolled conditions
* Has known allergies, hypersensitivity, intolerance, or any contraindication to seltorexant or its excipients

Where this trial is running

Doral, Florida and 4 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Depressive Disorder, Major
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.