{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:11:23Z","timestamp":1780913483080,"version":"3.54.1"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Viloxazine is a serotonin\u2013norepinephrine modulatory agent that was recently approved by the U.S. Food and Drug Administration for the treatment of attention\u2010deficit\/hyperactivity disorder (ADHD) in children, adolescents, and adults. This review aims to summarize the regulatory history, pharmacology, pharmacokinetics, clinical efficacy, safety, and current therapeutic role of viloxazine, while also highlighting gaps in the evidence and future research directions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A narrative literature review was conducted using PubMed, Google Scholar, and FDA regulatory documents. Relevant peer\u2010reviewed articles, including clinical trials, reviews, meta\u2010analyses, and prescribing information, were screened for data on viloxazine's historical antidepressant use, mechanism of action, pharmacokinetics, efficacy in ADHD, safety profile, drug interactions, and comparative effectiveness. Non\u2010peer\u2010reviewed sources were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Viloxazine was originally marketed in Europe in the 1970s as an antidepressant and showed a favorable safety profile over decades of use. Its pharmacological profile includes moderate norepinephrine reuptake inhibition with additional serotonergic activity, particularly 5\u2010HT2C agonism and 5\u2010HT2B antagonism, which supported its repurposing as an extended\u2010release formulation for ADHD. Multiple randomized, placebo\u2010controlled trials demonstrated that viloxazine extended\u2010release significantly improves ADHD symptoms in pediatric, adolescent, and adult populations. Reported effect sizes were generally smaller than those of stimulants but comparable to atomoxetine. The most common adverse events were somnolence, headache, nausea, decreased appetite, and insomnia. Viloxazine also has a pharmacokinetic profile compatible with once\u2010daily dosing, although clinically relevant drug interactions may occur through CYP1A2 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Viloxazine expands the range of non\u2010stimulant treatment options for ADHD and represents a successful example of drug repurposing in neuropsychiatry. Current evidence supports its efficacy and acceptable tolerability across the lifespan, particularly for patients who do not tolerate or respond adequately to stimulants. Nevertheless, evidence for its use beyond ADHD remains limited, and future studies should focus on head\u2010to\u2010head comparisons with other ADHD therapies, long\u2010term safety and efficacy, predictors of response, and potential off\u2010label psychiatric applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70839","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:58:56Z","timestamp":1775620736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Viloxazine Paradox: A Noradrenergic Agent's Journey From Antidepressant Obscurity to\n                    <scp>ADHD<\/scp>\n                    Precision Therapy"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8721-3764","authenticated-orcid":false,"given":"Ghaith K.","family":"Mansour","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3496-5158","authenticated-orcid":false,"given":"Sabry Babiker H.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Faulty of Medicine and Health Sciences International University of Africa  Khartoum Sudan"},{"name":"Clinical Skills Department, General Medicine Practice Program, Batterjee Medical College  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6259-1045","authenticated-orcid":false,"given":"Sajjad Ghanim","family":"Al\u2010Badri","sequence":"additional","affiliation":[{"name":"College of Medicine University of Warith Al\u2010Anbiyaa  Karbala Iraq"},{"name":"College of Medicine University of Baghdad  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Gamaleldin Abdulrahim","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Faculty Medicine and Health Sciences International University of Africa  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-6601","authenticated-orcid":false,"given":"Dina Essam","family":"Abo\u2010elnour","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Zagazig University  Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_15_2_1","volume-title":"Qelbree (Viloxazine Hydrochloride) [Prescribing Information]","author":"U.S. Food and DrugAdministration","year":"2021"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/JEP.S256586"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010021\u201000825\u2010w"},{"key":"e_1_2_15_5_1","volume-title":"Qelbree (Viloxazine Extended\u2010Release Capsules) Approval Package","author":"U.S. Food and Drug Administration","year":"2021"},{"key":"e_1_2_15_6_1","unstructured":"B. M.MathewandM. V.Pellegrini \u201cViloxazine \u201d(2025) http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34003459."},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.789982"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2020.05.021"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010022\u201000938\u2010w"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010023\u201001023\u20106"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.64719\/pb.4401"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010024\u201001120\u20100"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.70839","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:38:21Z","timestamp":1780911501000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.70839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cns.70839"],"URL":"https:\/\/doi.org\/10.1002\/cns.70839","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70839"}}