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Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk\u2010of\u2010bias assessment. Outcomes included change in monthly headache days, \u226550% responder rate, and validated patient\u2010reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 217 studies met inclusion criteria. For episodic migraine, high\u2010confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate\u2010confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low\u2010confidence evidence suggesting possible benefit. For chronic migraine, high\u2010confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate\u2010confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient\u2010reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High\u2010 and moderate\u2010confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient\u2010reported outcomes across multiple validated measures. These conclusions informed the development of evidence\u2010based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70200","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:01:10Z","timestamp":1788210070000},"page":"1971-1990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults"],"prefix":"10.1111","volume":"66","author":[{"given":"Tamara","family":"Pringsheim","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, Psychiatry, Pediatrics, and Community Health Sciences University of Calgary  Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don 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