{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:29:30Z","timestamp":1791419370968,"version":"4.3.3"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013410","name":"LivaNova","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010710","name":"PLC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005227","name":"Centers for Medicare & Medicaid Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Greater levels of treatment resistance in major depressive disorder (MDD) are associated with lower rates of initial benefit and higher rates of relapse (lower durability).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Characterize depressive symptoms, function, and quality of life (QoL) over 24\u00a0months of adjunctive vagus nerve stimulation (VNS) in participants with markedly treatment-resistant depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Prospective, open-label, single-arm, long-term extension study (RECOVER) conducted from September 2019 to April 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Outpatient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Adults with moderate\u2013severe MDD with \u2265 4 failed antidepressant trials in the current episode, randomized to blinded, adjunctive VNS for 12\u00a0months, who subsequently received open-label, adjunctive VNS for 12 additional months (n\u2009=\u2009214).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Vagus nerve stimulation and concomitant psychotropic medications and interventional psychiatric modalities (electroconvulsive therapy, transcranial magnetic stimulation, and ketamine\/esketamine) were characterized over the 12-month extension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The durability of benefit achieved at 12\u00a0months was assessed at 18 and 24\u00a0months for depressive symptoms (3 scales), daily function, QoL, a tripartite composite of all 3 domains, and the Clinical Global Impression\u2013Improvement (CGI-I) scale (overall improvement). Loss of benefit and relapse were assessed, along with the emergence of meaningful benefit in participants without benefit at 12\u00a0months. Substantial benefit (at least 50% symptom reduction from baseline; CGI-I of 1 or 2; tripartite measures with at least 2 of 3 subscales evidencing benefit) and meaningful benefit thresholds for symptoms (at least 30% reduction from baseline), function, QoL, CGI-I, and the tripartite measure were set a priori.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most participants with substantial benefit maintained their benefit (18-month median\u2009=\u200978.8%; 24-month median\u2009=\u200979.0% across 5 measures), as did participants with at least meaningful benefit at 12\u00a0months (18-month median\u2009=\u200983.1%; 24-month median\u2009=\u200981.3% across 7 measures). Furthermore, many participants with no meaningful benefit at 12\u00a0months achieved it at 18 (median\u2009=\u200930.6%) and 24 (median\u2009=\u200937.8%) months. The strong maintenance of benefit was not accounted for by changes in psychotropic medications or interventional psychiatric modalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Depressive symptom, daily function, and QoL benefits obtained after 12\u00a0months of adjunctive VNS were sustained in about 80% of participants continuing VNS. Approximately 30% with no meaningful benefit at 12\u00a0months accrued increased benefit over the subsequent year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf080","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T12:49:26Z","timestamp":1766234966000},"source":"Crossref","is-referenced-by-count":11,"title":["Durability of the benefit of vagus nerve stimulation in markedly treatment-resistant major depression: a RECOVER trial report"],"prefix":"10.1093","volume":"29","author":[{"given":"Charles R","family":"Conway","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Washington University in St Louis , St Louis, MO ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustus John","family":"Rush","sequence":"additional","affiliation":[{"name":"Duke-NUS Medical School ,","place":["Singapore"]},{"name":"Curbstone Consultant LLC , Dallas, TX ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T","family":"Aaronson","sequence":"additional","affiliation":[{"name":"Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt Health System , Baltimore, MD ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T","family":"Bunker","sequence":"additional","affiliation":[{"name":"LivaNova PLC (or a subsidiary) , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Gordon","sequence":"additional","affiliation":[{"name":"LivaNova PLC (or a subsidiary) , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"George","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Medical University of South Carolina , Charleston, SC ,","place":["United States"]},{"name":"Ralph H. 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