{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:54:39Z","timestamp":1780592079372,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Migraine is a common neurological condition marked by unilateral recurrent pulsating headaches, often associated with systemic signs and symptoms. Recently, calcitonin gene-related peptide (CGRP) antagonists, including atogepant, an oral CGRP receptor antagonist, have emerged as effective and safe treatments. The current study sought to assess the efficacy and safety of atogepant for preventing episodic migraines in adults. Methods: A comprehensive search, following PRISMA guidelines, was conducted using PubMed, Web of Science, and Cochrane Library to identify randomized, double-blind, placebo-controlled trials published up to June 2024. Results: The studies included adult participants with episodic migraine treated with atogepant. The primary outcomes assessed were changes in mean monthly migraine days (MMDs) and monthly headache days (MHDs) over 12 weeks. Secondary outcomes included reduction in acute medication use, 50% responder rates, and adverse events. A meta-analysis using a random-effects model was performed to evaluate efficacy and safety. Six trials with 4569 participants were included. Atogepant significantly reduced mean monthly migraine days (MMDs) and monthly headache days (MHDs) compared to placebo at all doses (10 mg, 30 mg, 60 mg), with the 60 mg dose showing the greatest reduction (mean difference: \u22121.48 days, p &lt; 0.001). Significant reductions in acute medication use and improved 50% responder rates were also observed for all doses. The safety profile of atogepant was favorable, with common adverse events being mild to moderate, such as constipation and nausea. There were no significant differences in serious adverse events between the atogepant and placebo groups. Conclusions: Atogepant is an effective and well-tolerated option for preventing episodic migraines, showing significant reductions in migraine frequency and acute medication use. However, further studies are necessary to assess its long-term safety and efficacy, especially at higher doses, and to investigate its potential role in personalized treatment strategies for migraine prevention.<\/jats:p>","DOI":"10.3390\/jcm13226713","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T04:02:54Z","timestamp":1731038574000},"page":"6713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety and Efficacy of Atogepant for the Preventive Treatment of Migraines in Adults: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0046-4638","authenticated-orcid":false,"given":"Abdulrahim Saleh","family":"Alrasheed","sequence":"first","affiliation":[{"name":"College of Medicine, King Faisal University, AlAhsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taif Mansour","family":"Almaqboul","sequence":"additional","affiliation":[{"name":"College of Medicine, Batterjee Medical College, Jeddah 21442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem Ali","family":"Alshamrani","sequence":"additional","affiliation":[{"name":"College of Medicine, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor Mohammad","family":"AlMohish","sequence":"additional","affiliation":[{"name":"Neurology Department, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Khobar 34445, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6992-5341","authenticated-orcid":false,"given":"Majed Mohammad","family":"Alabdali","sequence":"additional","affiliation":[{"name":"Neurology Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Khobar 34445, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1212\/01.wnl.0000252808.97649.21","article-title":"Migraine prevalence, disease burden, and the need for preventive therapy","volume":"68","author":"Lipton","year":"2007","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1129-2377-14-1","article-title":"Migraine: The seventh disabler","volume":"14","author":"Steiner","year":"2013","journal-title":"J. Headache Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s10194-020-01208-0","article-title":"Migraine remains second among the world\u2019s causes of disability, and first among young women: Findings from GBD2019","volume":"21","author":"Steiner","year":"2020","journal-title":"Headache Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1001\/jama.290.18.2443","article-title":"Lost Productive Time and Cost Due to Common Pain Conditions in the US Workforce","volume":"290","author":"Stewart","year":"2003","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(20)32160-7","article-title":"Migraine: Epidemiology and systems of care","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1007\/s10072-013-1387-8","article-title":"Burden of migraine: International perspectives","volume":"34","author":"Leonardi","year":"2013","journal-title":"Neurol. Sci."},{"key":"ref_7","first-page":"1","article-title":"The International Classification of Headache Disorders, 3rd edition","volume":"1","author":"Olesen","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1111\/j.1526-4610.2012.02223.x","article-title":"Chronic migraine prevalence, disability, and sociodemographic factors: Results from the American migraine prevalence and prevention study","volume":"52","author":"Buse","year":"2012","journal-title":"Headache"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E2215499","DOI":"10.1001\/jamanetworkopen.2022.15499","article-title":"Rates of Response to Atogepant for Migraine Prophylaxis among Adults: A Secondary Analysis of a Randomized Clinical Trial","volume":"5","author":"Lipton","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s11916-011-0233-z","article-title":"Defining the differences between episodic migraine and chronic migraine","volume":"16","author":"Katsarava","year":"2012","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1056\/NEJMoa2035908","article-title":"Atogepant for the Preventive Treatment of Migraine","volume":"385","author":"Ailani","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s10194-022-01391-2","article-title":"The efficacy and safety of atogepant for the prophylactic treatment of migraine: Evidence from randomized controlled trials","volume":"23","author":"Tao","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s10194-021-01252-4","article-title":"Burden and Attitude to Resistant and Refractory (BARR) Study Group; Burden and attitude to resistant and refractory migraine: A survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance","volume":"22","author":"Sacco","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of Migraine: A Disorder of Sensory Processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S0140-6736(18)30478-1","article-title":"Migraine","volume":"391","author":"Dodick","year":"2018","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1007\/s40120-022-00370-8","article-title":"Atogepant for the Prevention of Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Efficacy and Safety","volume":"11","author":"Lattanzi","year":"2022","journal-title":"Neurol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tepper, D. (2024, June 30). Gepants. Headache: The Journal of Head and Face Pain\u00a9 2020 American Headache Society Published by Wiley Periodicals, Inc. 1037\u20131039. Available online: https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/epdf\/10.1111\/head.13791.","DOI":"10.1111\/head.13791"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3331024241235156","DOI":"10.1177\/03331024241235156","article-title":"Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis","volume":"44","author":"Tassorelli","year":"2024","journal-title":"Cephalalgia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20503121221128688","DOI":"10.1177\/20503121221128688","article-title":"Atogepant for the prevention of episodic migraine in adults","volume":"10","author":"Switzer","year":"2022","journal-title":"SAGE Open Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The International Classification of Headache Disorders, 3rd edition (beta version)","volume":"33","author":"Schiffman","year":"2013","journal-title":"Cephalalgia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4082\/kjfm.23.0034","article-title":"RoBANS 2: A Revised Risk of Bias Assessment Tool for Nonrandomized Studies of Interventions","volume":"44","author":"Seo","year":"2023","journal-title":"Korean J. Fam. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"ref_24","unstructured":"Book Series, C., Higgins, J.P., and Green, S. (2008). Cochrane Handbook for Systematic Reviews of Interventions, The Cochrane Collaboration\u00ae."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/03331024211042385","article-title":"Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial","volume":"42","author":"Schwedt","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S1474-4422(20)30234-9","article-title":"Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: A double-blind, randomised phase 2b\/3 trial","volume":"19","author":"Goadsby","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E764","DOI":"10.1212\/WNL.0000000000201568","article-title":"Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial","volume":"100","author":"Lipton","year":"2023","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S1474-4422(24)00025-5","article-title":"Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): A randomised, placebo-controlled, phase 3b trial","volume":"23","author":"Tassorelli","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s10194-024-01783-6","article-title":"Sustained response to atogepant in episodic migraine: Post hoc analyses of a 12-week randomized trial and a 52-week long-term safety trial","volume":"25","author":"Lipton","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s40259-022-00530-0","article-title":"Calcitonin Gene-Related Peptide (CGRP)-Targeted Monoclonal Antibodies and Antagonists in Migraine: Current Evidence and Rationale","volume":"36","author":"Cohen","year":"2022","journal-title":"BioDrugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s10194-024-01822-2","article-title":"Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: A systematic review and meta-analysis","volume":"25","author":"Hou","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s11940-024-00803-9","article-title":"Efficacy and Safety of Atogepant for Preventing Chronic and Episodic Migraines: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"26","author":"Lopes","year":"2024","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Feigin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s10194-023-01594-1","article-title":"The comparative effectiveness of migraine preventive drugs: A systematic review and network meta-analysis","volume":"24","author":"Lampl","year":"2023","journal-title":"J. Headache Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/head.14692","article-title":"American Headache Society.; Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update","volume":"64","author":"Charles","year":"2024","journal-title":"Headache"},{"key":"ref_36","unstructured":"National Institute for Health and Care Excellence (NICE) (2024, June 30). Atogepant for Preventing Migraine Technology Appraisal Guidance. Available online: https:\/\/www.nice.org.uk\/guidance\/ta973\/resources\/atogepant-for-preventing-migraine-pdf-82615848254917."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Raja, A., Asim, R., Shuja, M.H., Raja, S., Saleh Muhammad, T., Bajaj, S., Ansari, A.H., Ali, H., Magsi, I.A., and Faridi, M.H. (2024). Atogepant for Migraine Prevention: A Meta-Analysis of Safety and Efficacy in Adults. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1468961"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/22\/6713\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:28:36Z","timestamp":1760113716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/22\/6713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":37,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["jcm13226713"],"URL":"https:\/\/doi.org\/10.3390\/jcm13226713","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]}}}