Trial reportThe international journal of neuropsychopharmacology2026
Safety, tolerability, and preliminary efficacy of seltorexant versus quetiapine extended release as adjunctive therapy in major depressive disorder: a randomized, flexible-dose, 6-month, parallel-group, exploratory study.
Trial report in The international journal of neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03321526 (A 6-Month, Multicenter, Double-Blind, Randomized, Flexible-Dose, Parallel-Group Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Subjects With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy), which is not on this map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A 6-Month, Multicenter, Double-Blind, Randomized, Flexible-Dose, Parallel-Group Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Subjects With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
Who cites it
1 citing paper in PubMed.
- Acute Onset of Suicidal Ideation after Starting Lemborexant in a Patient with a Mood Disorder.Sleep science (Sao Paulo, Brazil) · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
importanceSeltorexant, a selective orexin-2 receptor (OX2R) antagonist, has demonstrated antidepressant effects in major depressive disorder (MDD), particularly among patients with higher baseline insomnia symptoms.
objectiveTo investigate flexibly dosed seltorexant vs flexibly dosed quetiapine extended release (quetiapine-XR) as adjunctive treatment to a selective serotonin (SSRI) or serotonin-norepinephrine (SNRI) reuptake inhibitor.
settingOutpatient.
designRandomized, active-controlled, multicenter, exploratory phase 2 study with screening (≤4 weeks), double-blind treatment (24 weeks), and post-treatment follow-up (2 weeks) phases.
participantsPatients with MDD and inadequate response to 1-3 SSRIs/SNRIs, including an ongoing SSRI/SNRI, in the current depressive episode.
interventionsFlexibly dosed seltorexant (20 or 40 mg) or quetiapine-XR (150 or 300 mg, with 2-day initial dosing of 50 mg) once daily as adjunctive therapy to an SSRI/SNRI. Randomization (1:1) was stratified by baseline Insomnia Severity Index total score (≥15 vs <15). Safety, tolerability, and preliminary efficacy were evaluated. MAIN OUTCOMES AND MEASURES: Primary efficacy endpoint was time to all-cause study drug discontinuation. Secondary efficacy endpoints included change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Subgroup analyses included MADRS change by mode dose (MD; most frequent daily dose received by a patient during the study). Safety and tolerability also were assessed.
resultsTime to all-cause discontinuation (estimated 25th percentile [80% CI]: seltorexant, 62 [38, 83] days vs quetiapine-XR, 42 [35, 61] days; hazard ratio [80% CI]: 0.83 [0.6, 1.2]) and all-cause discontinuation (seltorexant, 41.2% vs quetiapine-XR, 47.1%; 2-sided P = .5355) did not differ significantly between treatment groups. For the seltorexant 20-mg MD group, MADRS total scores consistently improved over time and reductions were numerically greater at weeks 18 and 24 versus the seltorexant 40-mg MD and the combined quetiapine-XR groups, and patients with higher baseline insomnia symptoms had greater improvement in MADRS total score, consistent with prior studies showing efficacy at 20 but not 40 mg. Treatment-emergent adverse event rates were 65.4% for seltorexant and 80.8% for quetiapine-XR. CONCLUSIONS AND RELEVANCE: Results support the favorable tolerability and preliminary efficacy of seltorexant 20 mg daily as adjunctive treatment in patients with MDD, especially those with insomnia symptoms, and suggest potential approaches to differentiate seltorexant from quetiapine-XR in future adequately powered studies.
trial registrationClinicaltrials.gov identifier: NCT03321526.
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