{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:49:04Z","timestamp":1790628544414,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research & Development, LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Seltorexant, a selective antagonist of human orexin-2 receptors, demonstrated antidepressant effects in a previous exploratory study in patients with major depressive disorder (MDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To replicate and extend this observation, a double-blind, adaptive dose-finding study was performed in patients with MDD who had an inadequate response to 1\u20133 selective serotonin\/serotonin-norepinephrine reuptake inhibitors in the current episode. Patients were randomized (2:1:1) to placebo or seltorexant (20 mg or 40 mg) once-daily, administered adjunctively to the antidepressant the patient had been receiving at screening. After an interim analysis (6 weeks post-randomization of 160th patient), newly recruited patients randomly received (3:3:1) placebo or seltorexant 10 mg or 20 mg; the 40-mg dose was no longer assigned. Patients were stratified by baseline Insomnia Severity Index (ISI) scores (ISI\u2009\u2265\u200915 vs &amp;lt;\u200915). The primary endpoint was change from baseline Montgomery-\u00c5sberg Depression Rating Scale (MADRS) total score at week 6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mixed-Model for Repeated Measures analysis showed a greater improvement in MADRS total score in the seltorexant 20-mg group vs placebo at weeks 3 and 6; least-square means difference (90% CI): \u22124.5 (\u22126.96; \u22122.07), P\u2009=\u2009.003; and \u22123.1 (\u22126.13; \u22120.16), P\u2009=\u2009.083, respectively. The improvement in MADRS score at week 6 for seltorexant 20 mg was greater in patients with baseline ISI \u2265 15 vs those with ISI &amp;lt; 15; least-square means difference (90% CI) vs placebo: \u22124.9 (\u22128.98; \u22120.80) and \u22120.7 (\u22125.16; 3.76), respectively. The most common (\u22655%) adverse events with seltorexant were somnolence, headache, and nausea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A clinically meaningful reduction of depressive symptoms was observed for seltorexant 20 mg. In the subset of patients with sleep disturbance (ISI \u2265 15), a larger treatment difference between seltorexant 20 mg and placebo was observed, warranting further investigation. No new safety signal was identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier: NCT03227224<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Previous presentation<\/jats:title>\n                    <jats:p>Poster presented at 58th Annual Meeting of American College of Neuropsychopharmacology (ACNP), December 8\u201311, 2019, Orlando, FL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ijnp\/pyab050","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T07:10:55Z","timestamp":1627456255000},"page":"965-976","source":"Crossref","is-referenced-by-count":63,"title":["Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8868-3704","authenticated-orcid":false,"given":"Adam","family":"Savitz","sequence":"first","affiliation":[{"name":"Janssen Research & Development, LLC, Titusville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Wajs","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Fremont, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Titusville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Etropolski","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Titusville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E","family":"Thase","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, and Corporal Michael J. 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