{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:11:01Z","timestamp":1783599061418,"version":"3.55.0"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Psychopharmacology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Treatment-resistant depression (TRD) remains a major clinical challenge, and long-term real-world data on intranasal esketamine are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To describe long-term dosing patterns and clinical outcomes associated with intranasal esketamine in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Single-center observational cohort study with descriptive analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We analyzed 45 patients with TRD treated with intranasal esketamine in a naturalistic setting, with follow-up extending up to 260\u2009weeks. Esketamine was used adjunctively with ongoing oral antidepressants. Outcomes included the Montgomery\u2013\u00c5sberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Glasgow Antipsychotic Side-effect Scale (GASS). Treatment patterns were summarized using person-time (person-weeks).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Baseline MADRS was 40.0 (SD 4.63). Mean MADRS decreased to 22.9 (SD 7.99) at week 4 and to 9.70 (SD 5.35) at week 52, with mean scores remaining around 9\u201310 at later time points among patients with available follow-up. Eight patients (17.8%) discontinued treatment (lack of efficacy\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20094; intolerable adverse effects\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20093; lost to follow-up\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20091). No treatment-emergent hypomania or manic symptoms were observed; YMRS scores decreased over time. GASS scores were low overall, with median values of 0 from week 13 onwards.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In a real-world TRD cohort with complex comorbidities, intranasal esketamine used adjunctively was associated with sustained symptom improvement and a favorable long-term safety profile among patients who continued treatment, with dosing evolving from induction to individualized maintenance schedules. Findings are limited by the observational design, concomitant treatments, and survivor bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20451253261437597","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:34:04Z","timestamp":1776753244000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Intranasal esketamine in treatment-resistant depression: long-term dosing patterns and clinical outcomes in a 5-year observational study"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-5248","authenticated-orcid":false,"given":"Alessandro","family":"Cuomo","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, ON, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4733-2523","authenticated-orcid":false,"given":"Roger S.","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Koukouna","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Pinzi","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Pardossi","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Firenzuoli","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Barill\u00e0","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Carmellini","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Alamia","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fagiolini","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Molecular Medicine, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.02.023"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(02)01670-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2006.163.11.1905"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-019-2222-4"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.201300059"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v63n1102"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.11.124"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2022.3352"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2022.114749"},{"key":"e_1_3_4_11_2","unstructured":"European Medicines Agency. 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