Seltorexant
Seltorexant improves objective sleep over days and produced a modest six-week depression result in patients with insomnia symptoms. It remained investigational, and its 2026 cognition signal came from a post-hoc comparison with sedating quetiapine.
Selective orexin-2 receptor antagonist
- A five-day 40 mg crossover and a 14-day 10/20 mg trial improved sleep latency and maintenance.
- The placebo-controlled phase 3 MADRS advantage was 2.6 points in a restricted 419-person efficacy set.
- Two quetiapine trials had no placebo; the 102-person pilot and 756-person phase 3 are separate studies.
- No healthy-rested cognitive enhancement, strength or longevity trial was found.
Is seltorexant the same as lemborexant?
No. Seltorexant selectively blocks OX2R and remains investigational. Lemborexant blocks OX1R and OX2R and has separate approvals.
No approved label exists to settle routine contraindications, interaction management or postmarketing risk for seltorexant.
PubChem CID 86278359 · identity
Government chemical database
National Center for Biotechnology Information. PubChem Compound Summary for CID 86278359, Seltorexant. National Library of Medicine.
The record identifies seltorexant/JNJ-42847922/MIN-202 as C21H22FN7O, molecular weight 407.4 g/mol, CAS 1452539-75-1.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
Chemical identity does not establish approval or clinical efficacy.
Read the original sourceCurrent recruiting phase 3 · investigational status
Clinical trial registry
Janssen Research & Development. NCT07573176. A Study of Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder. ClinicalTrials.gov. Last update posted June 5, 2026.
The record identifies seltorexant as an investigational product in a recruiting phase 3 monotherapy program, with no results posted.
- Participants / model
- Planned adults aged 18-74 with MDD
- Treatment
- Seltorexant or placebo in a double-blind phase with open-label continuation
- Study design
- Randomized phase 3 trial registry without results
- Funding
- Janssen
A recruiting trial is not evidence of efficacy and does not confer approval.
Read the original sourceHow much sleep benefit has been measured?
Short randomized studies found faster sleep onset and less wake time after sleep onset, with no long-term placebo-controlled insomnia program.
In the five-day crossover, 27 completers receiving 40 mg gained 37.9 minutes of total sleep and shortened persistent-sleep latency by 29.9 minutes versus placebo after five doses.
In the 364-person 14-day study, 10 and 20 mg improved sleep latency and wake after sleep onset on nights 1 and 13. Four seltorexant participants stopped for asymptomatic ECG findings; one serious event occurred at 20 mg.
A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity.
Primary human randomized study
De Boer P, Drevets WC, Rofael H, et al. Journal of Psychopharmacology. 2018. PMID 29848147. DOI 10.1177/0269881118773745.
Among 27 completers, 40 mg improved objective sleep efficiency, total sleep time, latency and wake after sleep onset versus placebo after one and five doses.
- Participants / model
- 28 randomized adults with insomnia; 27 completed
- Follow-up
- Five days per condition
- Study design
- Randomized double-blind placebo crossover
The study proves short-term sleep pharmacology, not chronic treatment, cognition or approval.
Read the original sourceInsomnia dose finding · 364 treated for 14 days
Randomized placebo- and active-controlled trial
Mesens S, Krystal AD, Melkote R, Xu H, Pandina G, Saoud JB, Luthringer R, Savitz A, Drevets WC. Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(10):967-976. doi:10.1001/jamapsychiatry.2025.1999. PMID 40802194.
Among 364 treated adults with insomnia and no psychiatric comorbidity, 10 and 20 mg shortened polysomnographic sleep latency and reduced wake after sleep onset over 14 nights; 5 mg was less consistent. Four asymptomatic ECG-related discontinuations were reported.
- Participants / model
- 364 adults aged 18-85 with insomnia disorder and no psychiatric comorbidity
- Treatment
- Nightly oral seltorexant 5, 10, or 20 mg, placebo, or zolpidem
- Follow-up
- Fourteen days
- Study design
- Randomized double-blind placebo- and active-controlled dose-finding trial
- Funding
- Janssen
Short dose-finding study; data were collected in 2017-2019 and publication was delayed. It is not an approval trial for routine use.
Read the original sourceHow much did depression scores improve?
The placebo-controlled phase 3 found a 2.6-point six-week MADRS advantage for adjunctive 20 mg in a 419-person restricted efficacy set.
The sleep-item-excluded MADRS difference was 2.0 points. Removing sleep items shows the result was not entirely a sleep-score artifact, but the mean effect remained modest.
Phase 2 patterns repeatedly favored 20 mg over 40 mg. One adaptive trial used a 90% interval and one-sided p value; an enriched monotherapy analysis included only 86 placebo nonresponders. More drug did not produce more benefit.
Phase 2b MDD · 287 randomized
Phase 2b randomized controlled trial
Savitz A, Wajs E, Zhang Y, Xu H, Etropolski M, Thase ME, Drevets WC. Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study. International Journal of Neuropsychopharmacology. 2021;24(12):965-976. doi:10.1093/ijnp/pyab050. PMID 34324636.
In 287 randomized adults with MDD inadequately responsive to an SSRI/SNRI, six weeks of adjunctive seltorexant used adaptive randomization. The 20 mg arm's MADRS difference versus placebo was -3.1 points with a 90% CI of -6.13 to -0.16 and one-sided p=0.083; a baseline-insomnia subgroup showed a larger exploratory difference.
- Participants / model
- 287 adults with MDD and inadequate SSRI/SNRI response; 283 treated, 251 completed
- Treatment
- Adjunctive oral seltorexant 10, 20, or 40 mg versus placebo
- Follow-up
- Six weeks
- Study design
- Randomized placebo-controlled adaptive dose-finding trial
- Funding
- Janssen
Adaptive allocation, one-sided alpha, multiple doses, and the insomnia subgroup limit certainty; the result was not a conventional confirmatory phase 3 test.
Read the original sourceEnriched phase 2 · 128 total, 86 analyzed nonresponders
Randomized placebo-controlled trial
Mesens S, Kezic I, Van Der Ark P, Etropolski M, Pandina G, Benes H, Savitz A, Drevets WC. Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial. Molecular Psychiatry. 2025;30:2427-2435. doi:10.1038/s41380-024-02846-5. PMID 39663378.
The study enrolled 128 adults and used a placebo lead-in. The primary enriched analysis covered 86 placebo nonresponders; five-week HDRS-17 change was -7.0 with 20 mg, -5.5 with 40 mg, and -4.4 with placebo. The across-arm p value was 0.0456 and 20 mg versus placebo p=0.0049, without a monotonic dose response.
- Participants / model
- 128 adults with MDD; primary enriched analysis in 86 placebo lead-in nonresponders
- Treatment
- Oral seltorexant 20 mg, 40 mg, or placebo
- Follow-up
- Five weeks after placebo lead-in
- Study design
- Randomized double-blind enriched placebo-controlled trial
- Funding
- Janssen
Small enriched analysis, short duration, and nonmonotonic dose pattern limit generalization.
Read the original sourcePhase 3 registry · 588 randomized
Clinical trial registry with posted results
Janssen Research & Development. NCT04533529. A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Participants With Major Depressive Disorder and Insomnia Symptoms. ClinicalTrials.gov results record, updated May 12, 2026.
The completed phase 3 randomized 588 participants; 586 were dosed and the specified efficacy set included 419. At six weeks, adjunctive seltorexant 20 mg improved MADRS versus placebo by -2.6 points (95% CI -4.53 to -0.74; p=0.007), and the MADRS score excluding sleep items by -2.0 points (95% CI -3.75 to -0.28; p=0.023).
- Participants / model
- 588 randomized adults/older adults with MDD, insomnia symptoms, and inadequate antidepressant response; efficacy set 419
- Treatment
- Adjunctive oral seltorexant 20 mg or placebo with ongoing antidepressant
- Follow-up
- Six-week double-blind phase plus follow-up
- Study design
- Randomized double-blind placebo-controlled phase 3 trial with registry results
- Funding
- Janssen
Registry-posted results are primary sponsor-submitted evidence but not a peer-reviewed full report; the efficacy set excluded some randomized participants based on prespecified symptom thresholds.
Read the original sourceWhat did the two quetiapine studies show?
They provide active-comparator data without a placebo effect. The 102-person phase 2 pilot and 756-person phase 3 are different trials.
The 24-week pilot found no difference in time to all-cause discontinuation: hazard ratio 0.83 with an 80% CI of 0.6 to 1.2. Favorable 20 mg mode-dose analyses grouped people by the dose most often received after randomization.
The 26-week phase 3 reported MADRS response in 57.4% with seltorexant and 53.4% with quetiapine. Treatment-related events were about 29% versus 52%. It included Russian and Ukrainian sites, but no country-specific effect was reported.
Seltorexant versus quetiapine XR as adjunctive treatment in major depressive disorder: randomized phase 2 study.
Primary human randomized active-comparator study
Pinter C, Thase ME, McIntyre RS, et al. International Journal of Neuropsychopharmacology. 2026. PMID 41795948.
The 102-person pilot found no difference in time to all-cause discontinuation; mode-dose efficacy analyses were post-randomization subgroups.
- Participants / model
- 102 adults with MDD and insomnia symptoms, 51 per arm
- Follow-up
- 24 weeks
- Study design
- Double-blind active-comparator phase 2 trial
This is separate from the 756-person phase 3 quetiapine comparison and has no placebo arm.
Read the original sourceGlobal phase 3 · 756, including Russian sites
Sponsor clinical-study results summary
Janssen Pharmaceutica. Summary of Clinical Study Results, protocol 42847922MDD3005 / NCT04513912. August 20, 2024.
The 15-country phase 3 enrolled 756 participants, including sites in Russia and Ukraine. After 26 weeks, MADRS response proportions were similar with seltorexant and quetiapine and the difference was too small to establish a treatment difference. Possible treatment-related adverse events were reported in 29% of 366 seltorexant recipients and 52% of 390 quetiapine recipients.
- Participants / model
- 756 adults aged 18-74 with MDD, moderate-to-severe insomnia symptoms, and partial antidepressant response; 422 enrolled in Europe including Russia
- Treatment
- Nightly oral seltorexant or quetiapine extended release, added to ongoing antidepressant
- Follow-up
- Twenty-six weeks plus follow-up
- Study design
- Randomized double-blind active-comparator phase 3 trial
- Funding
- Janssen
The public plain-language summary does not provide a placebo comparison or exact country-by-country outcomes; 43 participants were excluded from the main analysis, including some Ukrainian data affected by the war.
Read the original sourceDoes site participation count as Russian replication?
No. Russian sites contributed to the 15-country quetiapine-controlled phase 3; the trial did not publish a separate Russian randomized estimate.
Similar response proportions against an active drug do not quantify absolute efficacy versus placebo or create an approval.
Global phase 3 · 756, including Russian sites
Sponsor clinical-study results summary
Janssen Pharmaceutica. Summary of Clinical Study Results, protocol 42847922MDD3005 / NCT04513912. August 20, 2024.
The 15-country phase 3 enrolled 756 participants, including sites in Russia and Ukraine. After 26 weeks, MADRS response proportions were similar with seltorexant and quetiapine and the difference was too small to establish a treatment difference. Possible treatment-related adverse events were reported in 29% of 366 seltorexant recipients and 52% of 390 quetiapine recipients.
- Participants / model
- 756 adults aged 18-74 with MDD, moderate-to-severe insomnia symptoms, and partial antidepressant response; 422 enrolled in Europe including Russia
- Treatment
- Nightly oral seltorexant or quetiapine extended release, added to ongoing antidepressant
- Follow-up
- Twenty-six weeks plus follow-up
- Study design
- Randomized double-blind active-comparator phase 3 trial
- Funding
- Janssen
The public plain-language summary does not provide a placebo comparison or exact country-by-country outcomes; 43 participants were excluded from the main analysis, including some Ukrainian data affected by the war.
Read the original sourceDid seltorexant improve cognition?
A 2026 sponsor poster reported small post-hoc differences versus quetiapine on two processing or executive measures. It did not show a nootropic effect.
At week 26, Symbol Sorting differed by 0.3 categories (95% CI 0.07 to 0.56; effect size 0.19). Reliable improvement was 12.4% versus 6.5% (nominal p=0.04). Word-list learning and Symbol Digit Matching mean differences were small and their confidence intervals included no effect.
The analysis had no placebo, no multiplicity correction, 70% to 86% test completion and a sedating comparator. Daytime healthy-subject dosing caused somnolence; lack of next-day residual effects was a safety finding, not enhancement.
Impact of seltorexant on cognitive performance of adults with major depressive disorder.
Primary sponsor conference report
Janssen/J&J. ASCP 2026 congress poster; post-hoc analysis of NCT04513912.
Small exploratory executive/processing-speed differences favored seltorexant over quetiapine, with no placebo and no multiplicity adjustment.
- Participants / model
- 756 treated adults with MDD and insomnia symptoms in the parent active-comparator phase 3
- Follow-up
- 26 weeks
- Study design
- Post-hoc cognitive analysis of randomized active-comparator trial
- Funding
- Sponsor-authored conference poster.
Entrants were not selected for cognitive impairment; completion varied and a sedating comparator prevents a nootropic inference.
Read the original sourceMultiple daytime administration of the selective orexin-2 receptor antagonist JNJ-42847922 induces somnolence in healthy subjects without residual central effects.
Primary human pharmacology study
van der Ark PD et al. Journal of Psychopharmacology. 2018. PMID 30182786.
Daytime administration caused expected somnolence, while measured central effects did not persist to the following day.
- Participants / model
- Healthy participants
- Follow-up
- Short repeated exposure
- Study design
- Randomized multiple-dose pharmacology study
A next-day null is a residual-safety result, not healthy cognitive enhancement during or after dosing.
Read the original sourceHow fast did the first-in-human suspension behave?
In healthy men given single oral-suspension doses, median Tmax was about 0.33 to 0.50 hours and terminal half-life about 2.02 to 2.44 hours.
Those numbers come from a sponsor protocol table. They may not transfer to later tablets, repeated bedtime dosing, women, older adults or depressed patients, and they do not define benefit duration.
Phase 1 protocol · healthy men, suspension PK
Clinical trial protocol
Janssen Research & Development. Clinical Study Protocol for JNJ-42847922 first-in-human single ascending oral dose study. Protocol document dated April 24, 2018, available in the ClinicalTrials.gov document archive for NCT03227224.
The protocol's completed phase 1 table describes 57 healthy men, 38 receiving active single doses as oral suspension, with rapid absorption (reported median Tmax about 0.33-0.50 hours) and terminal half-life about 2.02-2.44 hours across the cited cohorts.
- Participants / model
- 57 healthy men enrolled and completed; 38 received active drug
- Treatment
- Single oral suspension doses across ascending cohorts
- Follow-up
- Single-dose PK sampling
- Study design
- First-in-human randomized placebo-controlled dose-escalation protocol with results table
- Funding
- Janssen
These values come from single oral-suspension doses in healthy men; tablets, repeated dosing, patients, women, and older adults may differ.
Read the original sourceWhich safety limits are already visible?
Somnolence, headache and nausea recur in the program. Four asymptomatic ECG-related discontinuations occurred during the 14-day insomnia trial.
The depression trials monitored suicidality, withdrawal, metabolic measures and orexin-class sleep events. Without an approved label or long-term insomnia study, interaction and routine-use rules remain unsettled.
Insomnia dose finding · 364 treated for 14 days
Randomized placebo- and active-controlled trial
Mesens S, Krystal AD, Melkote R, Xu H, Pandina G, Saoud JB, Luthringer R, Savitz A, Drevets WC. Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(10):967-976. doi:10.1001/jamapsychiatry.2025.1999. PMID 40802194.
Among 364 treated adults with insomnia and no psychiatric comorbidity, 10 and 20 mg shortened polysomnographic sleep latency and reduced wake after sleep onset over 14 nights; 5 mg was less consistent. Four asymptomatic ECG-related discontinuations were reported.
- Participants / model
- 364 adults aged 18-85 with insomnia disorder and no psychiatric comorbidity
- Treatment
- Nightly oral seltorexant 5, 10, or 20 mg, placebo, or zolpidem
- Follow-up
- Fourteen days
- Study design
- Randomized double-blind placebo- and active-controlled dose-finding trial
- Funding
- Janssen
Short dose-finding study; data were collected in 2017-2019 and publication was delayed. It is not an approval trial for routine use.
Read the original sourceSeltorexant versus quetiapine XR as adjunctive treatment in major depressive disorder: randomized phase 2 study.
Primary human randomized active-comparator study
Pinter C, Thase ME, McIntyre RS, et al. International Journal of Neuropsychopharmacology. 2026. PMID 41795948.
The 102-person pilot found no difference in time to all-cause discontinuation; mode-dose efficacy analyses were post-randomization subgroups.
- Participants / model
- 102 adults with MDD and insomnia symptoms, 51 per arm
- Follow-up
- 24 weeks
- Study design
- Double-blind active-comparator phase 2 trial
This is separate from the 756-person phase 3 quetiapine comparison and has no placebo arm.
Read the original sourceGlobal phase 3 · 756, including Russian sites
Sponsor clinical-study results summary
Janssen Pharmaceutica. Summary of Clinical Study Results, protocol 42847922MDD3005 / NCT04513912. August 20, 2024.
The 15-country phase 3 enrolled 756 participants, including sites in Russia and Ukraine. After 26 weeks, MADRS response proportions were similar with seltorexant and quetiapine and the difference was too small to establish a treatment difference. Possible treatment-related adverse events were reported in 29% of 366 seltorexant recipients and 52% of 390 quetiapine recipients.
- Participants / model
- 756 adults aged 18-74 with MDD, moderate-to-severe insomnia symptoms, and partial antidepressant response; 422 enrolled in Europe including Russia
- Treatment
- Nightly oral seltorexant or quetiapine extended release, added to ongoing antidepressant
- Follow-up
- Twenty-six weeks plus follow-up
- Study design
- Randomized double-blind active-comparator phase 3 trial
- Funding
- Janssen
The public plain-language summary does not provide a placebo comparison or exact country-by-country outcomes; 43 participants were excluded from the main analysis, including some Ukrainian data affected by the war.
Read the original sourceCurrent recruiting phase 3 · investigational status
Clinical trial registry
Janssen Research & Development. NCT07573176. A Study of Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder. ClinicalTrials.gov. Last update posted June 5, 2026.
The record identifies seltorexant as an investigational product in a recruiting phase 3 monotherapy program, with no results posted.
- Participants / model
- Planned adults aged 18-74 with MDD
- Treatment
- Seltorexant or placebo in a double-blind phase with open-label continuation
- Study design
- Randomized phase 3 trial registry without results
- Funding
- Janssen
A recruiting trial is not evidence of efficacy and does not confer approval.
Read the original sourceDoes the Alzheimer program show neuroprotection?
No. The registered study targets sleep disturbance and agitation, and the registry posts no result; disease modification is not its primary endpoint.
The cited human studies do not report healthy-rested enhancement, dementia prevention, strength, or longevity outcomes.
A Study of Seltorexant in Participants With Probable Alzheimer's Disease
Primary trial registry
ClinicalTrials.gov NCT05307692.
The study targets sleep disturbance and agitation, and the registry posts no result; disease modification is not its primary endpoint.
- Participants / model
- People with probable Alzheimer disease and sleep disturbance/agitation
- Study design
- Registered randomized clinical study
The trial cannot support cognition, prevention or neuroprotection without results and relevant endpoints.
Read the original sourceWhy does seltorexant remain in B tier?
B reflects short objective insomnia efficacy and one modest placebo-controlled phase 3 depression effect. Seltorexant remained investigational, and the cognition analysis was exploratory.
A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity.
Primary human randomized study
De Boer P, Drevets WC, Rofael H, et al. Journal of Psychopharmacology. 2018. PMID 29848147. DOI 10.1177/0269881118773745.
Among 27 completers, 40 mg improved objective sleep efficiency, total sleep time, latency and wake after sleep onset versus placebo after one and five doses.
- Participants / model
- 28 randomized adults with insomnia; 27 completed
- Follow-up
- Five days per condition
- Study design
- Randomized double-blind placebo crossover
The study proves short-term sleep pharmacology, not chronic treatment, cognition or approval.
Read the original sourceInsomnia dose finding · 364 treated for 14 days
Randomized placebo- and active-controlled trial
Mesens S, Krystal AD, Melkote R, Xu H, Pandina G, Saoud JB, Luthringer R, Savitz A, Drevets WC. Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(10):967-976. doi:10.1001/jamapsychiatry.2025.1999. PMID 40802194.
Among 364 treated adults with insomnia and no psychiatric comorbidity, 10 and 20 mg shortened polysomnographic sleep latency and reduced wake after sleep onset over 14 nights; 5 mg was less consistent. Four asymptomatic ECG-related discontinuations were reported.
- Participants / model
- 364 adults aged 18-85 with insomnia disorder and no psychiatric comorbidity
- Treatment
- Nightly oral seltorexant 5, 10, or 20 mg, placebo, or zolpidem
- Follow-up
- Fourteen days
- Study design
- Randomized double-blind placebo- and active-controlled dose-finding trial
- Funding
- Janssen
Short dose-finding study; data were collected in 2017-2019 and publication was delayed. It is not an approval trial for routine use.
Read the original sourcePhase 3 registry · 588 randomized
Clinical trial registry with posted results
Janssen Research & Development. NCT04533529. A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Participants With Major Depressive Disorder and Insomnia Symptoms. ClinicalTrials.gov results record, updated May 12, 2026.
The completed phase 3 randomized 588 participants; 586 were dosed and the specified efficacy set included 419. At six weeks, adjunctive seltorexant 20 mg improved MADRS versus placebo by -2.6 points (95% CI -4.53 to -0.74; p=0.007), and the MADRS score excluding sleep items by -2.0 points (95% CI -3.75 to -0.28; p=0.023).
- Participants / model
- 588 randomized adults/older adults with MDD, insomnia symptoms, and inadequate antidepressant response; efficacy set 419
- Treatment
- Adjunctive oral seltorexant 20 mg or placebo with ongoing antidepressant
- Follow-up
- Six-week double-blind phase plus follow-up
- Study design
- Randomized double-blind placebo-controlled phase 3 trial with registry results
- Funding
- Janssen
Registry-posted results are primary sponsor-submitted evidence but not a peer-reviewed full report; the efficacy set excluded some randomized participants based on prespecified symptom thresholds.
Read the original sourceGlobal phase 3 · 756, including Russian sites
Sponsor clinical-study results summary
Janssen Pharmaceutica. Summary of Clinical Study Results, protocol 42847922MDD3005 / NCT04513912. August 20, 2024.
The 15-country phase 3 enrolled 756 participants, including sites in Russia and Ukraine. After 26 weeks, MADRS response proportions were similar with seltorexant and quetiapine and the difference was too small to establish a treatment difference. Possible treatment-related adverse events were reported in 29% of 366 seltorexant recipients and 52% of 390 quetiapine recipients.
- Participants / model
- 756 adults aged 18-74 with MDD, moderate-to-severe insomnia symptoms, and partial antidepressant response; 422 enrolled in Europe including Russia
- Treatment
- Nightly oral seltorexant or quetiapine extended release, added to ongoing antidepressant
- Follow-up
- Twenty-six weeks plus follow-up
- Study design
- Randomized double-blind active-comparator phase 3 trial
- Funding
- Janssen
The public plain-language summary does not provide a placebo comparison or exact country-by-country outcomes; 43 participants were excluded from the main analysis, including some Ukrainian data affected by the war.
Read the original sourceCurrent recruiting phase 3 · investigational status
Clinical trial registry
Janssen Research & Development. NCT07573176. A Study of Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder. ClinicalTrials.gov. Last update posted June 5, 2026.
The record identifies seltorexant as an investigational product in a recruiting phase 3 monotherapy program, with no results posted.
- Participants / model
- Planned adults aged 18-74 with MDD
- Treatment
- Seltorexant or placebo in a double-blind phase with open-label continuation
- Study design
- Randomized phase 3 trial registry without results
- Funding
- Janssen
A recruiting trial is not evidence of efficacy and does not confer approval.
Read the original sourceStudies and sources
PubChem CID 86278359 · identity
Government chemical database
National Center for Biotechnology Information. PubChem Compound Summary for CID 86278359, Seltorexant. National Library of Medicine.
The record identifies seltorexant/JNJ-42847922/MIN-202 as C21H22FN7O, molecular weight 407.4 g/mol, CAS 1452539-75-1.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
Chemical identity does not establish approval or clinical efficacy.
Read the original sourcePhase 2b MDD · 287 randomized
Phase 2b randomized controlled trial
Savitz A, Wajs E, Zhang Y, Xu H, Etropolski M, Thase ME, Drevets WC. Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study. International Journal of Neuropsychopharmacology. 2021;24(12):965-976. doi:10.1093/ijnp/pyab050. PMID 34324636.
In 287 randomized adults with MDD inadequately responsive to an SSRI/SNRI, six weeks of adjunctive seltorexant used adaptive randomization. The 20 mg arm's MADRS difference versus placebo was -3.1 points with a 90% CI of -6.13 to -0.16 and one-sided p=0.083; a baseline-insomnia subgroup showed a larger exploratory difference.
- Participants / model
- 287 adults with MDD and inadequate SSRI/SNRI response; 283 treated, 251 completed
- Treatment
- Adjunctive oral seltorexant 10, 20, or 40 mg versus placebo
- Follow-up
- Six weeks
- Study design
- Randomized placebo-controlled adaptive dose-finding trial
- Funding
- Janssen
Adaptive allocation, one-sided alpha, multiple doses, and the insomnia subgroup limit certainty; the result was not a conventional confirmatory phase 3 test.
Read the original sourceEnriched phase 2 · 128 total, 86 analyzed nonresponders
Randomized placebo-controlled trial
Mesens S, Kezic I, Van Der Ark P, Etropolski M, Pandina G, Benes H, Savitz A, Drevets WC. Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial. Molecular Psychiatry. 2025;30:2427-2435. doi:10.1038/s41380-024-02846-5. PMID 39663378.
The study enrolled 128 adults and used a placebo lead-in. The primary enriched analysis covered 86 placebo nonresponders; five-week HDRS-17 change was -7.0 with 20 mg, -5.5 with 40 mg, and -4.4 with placebo. The across-arm p value was 0.0456 and 20 mg versus placebo p=0.0049, without a monotonic dose response.
- Participants / model
- 128 adults with MDD; primary enriched analysis in 86 placebo lead-in nonresponders
- Treatment
- Oral seltorexant 20 mg, 40 mg, or placebo
- Follow-up
- Five weeks after placebo lead-in
- Study design
- Randomized double-blind enriched placebo-controlled trial
- Funding
- Janssen
Small enriched analysis, short duration, and nonmonotonic dose pattern limit generalization.
Read the original sourceInsomnia dose finding · 364 treated for 14 days
Randomized placebo- and active-controlled trial
Mesens S, Krystal AD, Melkote R, Xu H, Pandina G, Saoud JB, Luthringer R, Savitz A, Drevets WC. Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(10):967-976. doi:10.1001/jamapsychiatry.2025.1999. PMID 40802194.
Among 364 treated adults with insomnia and no psychiatric comorbidity, 10 and 20 mg shortened polysomnographic sleep latency and reduced wake after sleep onset over 14 nights; 5 mg was less consistent. Four asymptomatic ECG-related discontinuations were reported.
- Participants / model
- 364 adults aged 18-85 with insomnia disorder and no psychiatric comorbidity
- Treatment
- Nightly oral seltorexant 5, 10, or 20 mg, placebo, or zolpidem
- Follow-up
- Fourteen days
- Study design
- Randomized double-blind placebo- and active-controlled dose-finding trial
- Funding
- Janssen
Short dose-finding study; data were collected in 2017-2019 and publication was delayed. It is not an approval trial for routine use.
Read the original sourcePhase 3 registry · 588 randomized
Clinical trial registry with posted results
Janssen Research & Development. NCT04533529. A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Participants With Major Depressive Disorder and Insomnia Symptoms. ClinicalTrials.gov results record, updated May 12, 2026.
The completed phase 3 randomized 588 participants; 586 were dosed and the specified efficacy set included 419. At six weeks, adjunctive seltorexant 20 mg improved MADRS versus placebo by -2.6 points (95% CI -4.53 to -0.74; p=0.007), and the MADRS score excluding sleep items by -2.0 points (95% CI -3.75 to -0.28; p=0.023).
- Participants / model
- 588 randomized adults/older adults with MDD, insomnia symptoms, and inadequate antidepressant response; efficacy set 419
- Treatment
- Adjunctive oral seltorexant 20 mg or placebo with ongoing antidepressant
- Follow-up
- Six-week double-blind phase plus follow-up
- Study design
- Randomized double-blind placebo-controlled phase 3 trial with registry results
- Funding
- Janssen
Registry-posted results are primary sponsor-submitted evidence but not a peer-reviewed full report; the efficacy set excluded some randomized participants based on prespecified symptom thresholds.
Read the original sourceGlobal phase 3 · 756, including Russian sites
Sponsor clinical-study results summary
Janssen Pharmaceutica. Summary of Clinical Study Results, protocol 42847922MDD3005 / NCT04513912. August 20, 2024.
The 15-country phase 3 enrolled 756 participants, including sites in Russia and Ukraine. After 26 weeks, MADRS response proportions were similar with seltorexant and quetiapine and the difference was too small to establish a treatment difference. Possible treatment-related adverse events were reported in 29% of 366 seltorexant recipients and 52% of 390 quetiapine recipients.
- Participants / model
- 756 adults aged 18-74 with MDD, moderate-to-severe insomnia symptoms, and partial antidepressant response; 422 enrolled in Europe including Russia
- Treatment
- Nightly oral seltorexant or quetiapine extended release, added to ongoing antidepressant
- Follow-up
- Twenty-six weeks plus follow-up
- Study design
- Randomized double-blind active-comparator phase 3 trial
- Funding
- Janssen
The public plain-language summary does not provide a placebo comparison or exact country-by-country outcomes; 43 participants were excluded from the main analysis, including some Ukrainian data affected by the war.
Read the original sourcePhase 1 protocol · healthy men, suspension PK
Clinical trial protocol
Janssen Research & Development. Clinical Study Protocol for JNJ-42847922 first-in-human single ascending oral dose study. Protocol document dated April 24, 2018, available in the ClinicalTrials.gov document archive for NCT03227224.
The protocol's completed phase 1 table describes 57 healthy men, 38 receiving active single doses as oral suspension, with rapid absorption (reported median Tmax about 0.33-0.50 hours) and terminal half-life about 2.02-2.44 hours across the cited cohorts.
- Participants / model
- 57 healthy men enrolled and completed; 38 received active drug
- Treatment
- Single oral suspension doses across ascending cohorts
- Follow-up
- Single-dose PK sampling
- Study design
- First-in-human randomized placebo-controlled dose-escalation protocol with results table
- Funding
- Janssen
These values come from single oral-suspension doses in healthy men; tablets, repeated dosing, patients, women, and older adults may differ.
Read the original sourceCurrent recruiting phase 3 · investigational status
Clinical trial registry
Janssen Research & Development. NCT07573176. A Study of Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder. ClinicalTrials.gov. Last update posted June 5, 2026.
The record identifies seltorexant as an investigational product in a recruiting phase 3 monotherapy program, with no results posted.
- Participants / model
- Planned adults aged 18-74 with MDD
- Treatment
- Seltorexant or placebo in a double-blind phase with open-label continuation
- Study design
- Randomized phase 3 trial registry without results
- Funding
- Janssen
A recruiting trial is not evidence of efficacy and does not confer approval.
Read the original sourceA randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity.
Primary human randomized study
De Boer P, Drevets WC, Rofael H, et al. Journal of Psychopharmacology. 2018. PMID 29848147. DOI 10.1177/0269881118773745.
Among 27 completers, 40 mg improved objective sleep efficiency, total sleep time, latency and wake after sleep onset versus placebo after one and five doses.
- Participants / model
- 28 randomized adults with insomnia; 27 completed
- Follow-up
- Five days per condition
- Study design
- Randomized double-blind placebo crossover
The study proves short-term sleep pharmacology, not chronic treatment, cognition or approval.
Read the original sourceSeltorexant versus quetiapine XR as adjunctive treatment in major depressive disorder: randomized phase 2 study.
Primary human randomized active-comparator study
Pinter C, Thase ME, McIntyre RS, et al. International Journal of Neuropsychopharmacology. 2026. PMID 41795948.
The 102-person pilot found no difference in time to all-cause discontinuation; mode-dose efficacy analyses were post-randomization subgroups.
- Participants / model
- 102 adults with MDD and insomnia symptoms, 51 per arm
- Follow-up
- 24 weeks
- Study design
- Double-blind active-comparator phase 2 trial
This is separate from the 756-person phase 3 quetiapine comparison and has no placebo arm.
Read the original sourceMultiple daytime administration of the selective orexin-2 receptor antagonist JNJ-42847922 induces somnolence in healthy subjects without residual central effects.
Primary human pharmacology study
van der Ark PD et al. Journal of Psychopharmacology. 2018. PMID 30182786.
Daytime administration caused expected somnolence, while measured central effects did not persist to the following day.
- Participants / model
- Healthy participants
- Follow-up
- Short repeated exposure
- Study design
- Randomized multiple-dose pharmacology study
A next-day null is a residual-safety result, not healthy cognitive enhancement during or after dosing.
Read the original sourceImpact of seltorexant on cognitive performance of adults with major depressive disorder.
Primary sponsor conference report
Janssen/J&J. ASCP 2026 congress poster; post-hoc analysis of NCT04513912.
Small exploratory executive/processing-speed differences favored seltorexant over quetiapine, with no placebo and no multiplicity adjustment.
- Participants / model
- 756 treated adults with MDD and insomnia symptoms in the parent active-comparator phase 3
- Follow-up
- 26 weeks
- Study design
- Post-hoc cognitive analysis of randomized active-comparator trial
- Funding
- Sponsor-authored conference poster.
Entrants were not selected for cognitive impairment; completion varied and a sedating comparator prevents a nootropic inference.
Read the original sourceA Study of Seltorexant in Participants With Probable Alzheimer's Disease
Primary trial registry
ClinicalTrials.gov NCT05307692.
The study targets sleep disturbance and agitation, and the registry posts no result; disease modification is not its primary endpoint.
- Participants / model
- People with probable Alzheimer disease and sleep disturbance/agitation
- Study design
- Registered randomized clinical study
The trial cannot support cognition, prevention or neuroprotection without results and relevant endpoints.
Read the original sourceWhy is Seltorexant in B tier?
Seltorexant remains investigational. The cited trials show short objective insomnia efficacy and a modest placebo-controlled depression result concentrated at 20 mg; they do not establish healthy cognitive enhancement, long-term insomnia benefit, or longevity outcomes.