Trial results for a Phase 3 study evaluating seltorexant as adjunctive therapy for Major Depressive Disorder with Insomnia Symptoms (MDDIS) were posted on ClinicalTrials.gov on 2026-05-12. The study demonstrated that seltorexant 20 mg significantly reduced depressive symptoms, with a least square mean difference of -2.6 in MADRS total score compared to placebo (p=0.007).
Background
The study investigated seltorexant as an adjunctive therapy for adult and elderly participants diagnosed with Major Depressive Disorder with Insomnia Symptoms (MDDIS). These participants had previously shown an inadequate response to current antidepressant therapy, specifically with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
Trial design
The Phase 3 study (NCT04533529) enrolled 588 participants with Major Depressive Disorder. The trial's purpose was to assess the efficacy of seltorexant as adjunctive therapy compared with placebo, in combination with an antidepressant, for improving depressive symptoms in participants with MDDIS who had an inadequate response to prior SSRI or SNRI therapy. It also aimed to assess the long-term safety and tolerability of seltorexant as adjunctive therapy.
Key results
In the double-blind treatment phase, the study evaluated the change from baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score:
- Participants receiving placebo showed a mean change of -10.5 (Standard Deviation 10.26) units on the scale.
- Participants receiving seltorexant 20 mg showed a mean change of -12.9 (Standard Deviation 9.63) units on the scale.
A mixed model repeated measures (MMRM) analysis indicated a least square mean difference of -2.6 (95% CI: -4.53 to -0.74) between seltorexant 20 mg and placebo, with a p-value of 0.007.
Additional analyses from the open-label treatment phase reported:
- For Treatment Emergent Adverse Events (TEAEs), 167 participants who switched from placebo to seltorexant 20 mg experienced TEAEs, while 163 participants who continued on seltorexant 20 mg experienced TEAEs.
- For Treatment-Emergent Adverse Events of Special Interest (AESI), 10 participants in the placebo-to-seltorexant group and 8 participants in the seltorexant-to-seltorexant group experienced AESI.
- Changes from baseline in vital signs (blood pressure) included a mean change of 0.1 mmHg (Standard Deviation 8.22) and 0.5 mmHg (Standard Deviation 10.38) for the placebo-to-seltorexant group, and 0.9 mmHg (Standard Deviation 8.38) and -0.5 mmHg (Standard Deviation 11.29) for the seltorexant-to-seltorexant group.
- Changes from baseline in Body Mass Index (BMI) showed a mean change of 0.44 kg/m^2 (Standard Deviation 1.589) for the placebo-to-seltorexant group and 0.67 kg/m^2 (Standard Deviation 1.673) for the seltorexant-to-seltorexant group.
What this means
The results from this Phase 3 trial indicate that seltorexant 20 mg, when used as an adjunctive therapy to antidepressants, significantly improved depressive symptoms in adults and elderly participants with Major Depressive Disorder with Insomnia Symptoms who had not adequately responded to prior antidepressant treatment. The statistically significant reduction in MADRS total score suggests a potential clinical benefit for this patient population. The open-label phase provided some safety and tolerability data, including the incidence of treatment-emergent adverse events and changes in vital signs and BMI, which will be important for a comprehensive safety profile assessment.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04533529, titled "A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant and Long-term Safety Extension Treatment With Seltorexant", were posted on 2026-05-12 on clinicaltrials.gov.