Added Seltorexant Shows Robust Response With Fewer Adverse Events in MDD With Insomnia
In patients with major depressive disorder with insomnia symptoms (MDDIS), response rates were similarly robust with adjunctive seltorexant and quetiapine extended-release (XR), according to a poster presented at Psych Congress in San Diego, California.
However, rates of somnolence and study discontinuation were lower with seltorexant.
“Safety findings support the better tolerability of seltorexant as long-term adjunctive treatment for MDDIS,” wrote presenter Gahan Pandina, PhD, of Johnson & Johnson Innovative Medicine, Titusville, New Jersey, and coauthors.
Seltorexant is a first-in-class selective orexin-2 receptor antagonist developed to normalize hyperarousal and promote physiological sleep. The international phase 3 trial compared adjunctive treatment with investigational seltorexant compared with adjunctive quetiapine XR in 756 adult patients with DSM-5 major depressive disorder and moderate-to-severe insomnia symptoms who had an inadequate response to antidepressant treatment.
Among patients, 366 began seltorexant 20 mg and 390 began quetiapine XR at the labeled dosage while they continued treatment with their background selective serotonin reuptake inhibitor or serotonin–norepinephrine reuptake inhibitor.
At week 26, rates of patients achieving response, defined as a ≥50% improvement from the baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score, were 57.4% with added seltorexant and 53.4% with added quetiapine XR, according to the poster abstract. MADRS scores decreased an average 23.0 points with seltorexant and 22.7 points with quetiapine XR.
Body weight increased an average 0.5 kg with seltorexant and 2.1 kg with quetiapine XR over the 26-week period.
The incidence of somnolence was 6.3% with seltorexant compared with 24.1% with quetiapine XR. Meanwhile, rates of adverse events leading to study discontinuation were 5.7% with seltorexant and 11.3% with quetiapine XR.
The study was sponsored by Johnson & Johnson.
Reference
Pandina G. Seltorexant versus quetiapine extended release as adjunctive treatment in major depressive disorder with insomnia symptoms: phase 3 trial. Poster presented at Psych Congress; September 17-21, 2025; San Diego, California.
