Poster
25
(#25) Seltorexant Versus Quetiapine Extended Release as Adjunctive Treatment in Major Depressive Disorder With Insomnia Symptoms: Phase 3 Trial
Psych Congress 2025
Abstract: Background: Seltorexant, a first-in-class, selective, orexin-2 receptor antagonist, normalizes hyperarousal and promotes physiological sleep. Significant antidepressant effects and a favorable safety profile of adjunctive seltorexant versus placebo were shown in a phase 3, 6-week study in major depressive disorder with insomnia symptoms (MDDIS;NCT04533529). Here we present results of a trial comparing adjunctive seltorexant versus adjunctive quetiapine extended release(XR) as comparator in MDDIS (NCT04513912).
Methods: This 26-week, international, active-controlled study enrolled participants 18-74 years with DSM-5 diagnosis of MDD without psychotic features, with moderate-to-severe insomnia symptoms and inadequate response to 1-2 antidepressants. Participants were randomized 1:1 to seltorexant 20mg or quetiapineXR (labeled dosage) while continuing their background SSRI/SNRI. The primary endpoint was response rate (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at Week26. Secondary endpoints included change from baseline to Week26 in body weight (key) and in MADRS score. Safety was assessed.
Results: Of 757 participants randomized, 756 received ≥1 dose of study intervention(seltorexant:n=366;quetiapineXR:n=390). Week26 response rate was 57.4%(201/350) for seltorexant and 53.4%(194/363) for quetiapineXR; %difference:4.0(95%CI:-3.3,11.3). Mean change from baseline to Week26 in body weight(kg) was 0.5(SD:2.89,n=268) seltorexant and 2.1(SD:3.93,n=263) quetiapineXR (least squares[LS] mean difference:-1.7[95%CI:-2.23,-1.09]), and mean change in MADRS score was -23.0(SD:10.12,n=272) seltorexant and -22.7(SD:9.54,n=263) quetiapineXR (LS mean difference:-0.2[95%CI:-1.77,1.35]). Lower incidences of somnolence(6.3%[23/366];24.1%[94/390]) and adverse events leading to study intervention discontinuation(5.7%[21/366];11.3%[44/390]) were observed with seltorexant versus quetiapineXR.
Conclusions: Treatment arms demonstrated comparable robust response rates, without a statistical difference between groups. Safety findings support the better tolerability of seltorexant as long-term adjunctive treatment for MDDIS.
Short Description: The phase 3, 26-week, double-blind, active-controlled study (NCT04513912) of seltorexant versus quetiapine extended release(XR), each adjunctive to background SSRI/SNRI, in major depressive disorder with insomnia symptoms (MDDIS) did not achieve statistical significance on the primary endpoint. Both arms demonstrated comparable robust response rates. The higher incidences of weight gain, somnolence, and discontinuations due to adverse events with quetiapineXR support the favorable safety profile and better tolerability of seltorexant as long-term adjunctive treatment for MDDIS.
Name of Sponsoring Organization(s): This study was sponsored by Johnson & Johnson. YF, SM, GP, RK, YZ, HX, LX, CMC, WCD: Employees of Johnson & Johnson and may hold stock/stock options in Johnson & Johnson.
Methods: This 26-week, international, active-controlled study enrolled participants 18-74 years with DSM-5 diagnosis of MDD without psychotic features, with moderate-to-severe insomnia symptoms and inadequate response to 1-2 antidepressants. Participants were randomized 1:1 to seltorexant 20mg or quetiapineXR (labeled dosage) while continuing their background SSRI/SNRI. The primary endpoint was response rate (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at Week26. Secondary endpoints included change from baseline to Week26 in body weight (key) and in MADRS score. Safety was assessed.
Results: Of 757 participants randomized, 756 received ≥1 dose of study intervention(seltorexant:n=366;quetiapineXR:n=390). Week26 response rate was 57.4%(201/350) for seltorexant and 53.4%(194/363) for quetiapineXR; %difference:4.0(95%CI:-3.3,11.3). Mean change from baseline to Week26 in body weight(kg) was 0.5(SD:2.89,n=268) seltorexant and 2.1(SD:3.93,n=263) quetiapineXR (least squares[LS] mean difference:-1.7[95%CI:-2.23,-1.09]), and mean change in MADRS score was -23.0(SD:10.12,n=272) seltorexant and -22.7(SD:9.54,n=263) quetiapineXR (LS mean difference:-0.2[95%CI:-1.77,1.35]). Lower incidences of somnolence(6.3%[23/366];24.1%[94/390]) and adverse events leading to study intervention discontinuation(5.7%[21/366];11.3%[44/390]) were observed with seltorexant versus quetiapineXR.
Conclusions: Treatment arms demonstrated comparable robust response rates, without a statistical difference between groups. Safety findings support the better tolerability of seltorexant as long-term adjunctive treatment for MDDIS.
Short Description: The phase 3, 26-week, double-blind, active-controlled study (NCT04513912) of seltorexant versus quetiapine extended release(XR), each adjunctive to background SSRI/SNRI, in major depressive disorder with insomnia symptoms (MDDIS) did not achieve statistical significance on the primary endpoint. Both arms demonstrated comparable robust response rates. The higher incidences of weight gain, somnolence, and discontinuations due to adverse events with quetiapineXR support the favorable safety profile and better tolerability of seltorexant as long-term adjunctive treatment for MDDIS.
Name of Sponsoring Organization(s): This study was sponsored by Johnson & Johnson. YF, SM, GP, RK, YZ, HX, LX, CMC, WCD: Employees of Johnson & Johnson and may hold stock/stock options in Johnson & Johnson.
