{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:14:27Z","timestamp":1790007267012,"version":"4.0.1"},"reference-count":17,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100018074","name":"Weill Institute for Neurosciences, University of California, San Francisco","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Melatonin is effective for migraine prevention in adults. We hypothesized that melatonin would also be effective for migraine prevention in children and adolescents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a randomized, double\u2010blind trial of melatonin (3\u2009mg or 6\u2009mg) versus placebo for migraine prevention in 10\u201317 year\u2010olds with 4\u201328\/28 headache days at baseline. Participants were recruited from the UCSF Child &amp; Adolescent Headache Program, UCSF child neurology clinic, and social media advertisements. Migraine diagnosis was confirmed by a headache specialist. Participants completed an 8\u2010week single\u2010blind placebo run\u2010in. Those meeting randomization criteria (\u22654 headache days and \u226523\/28 electronic diary entries during weeks 5\u20138) were randomized 1:1:1 to placebo:melatonin 3\u2009mg:melatonin 6\u2009mg nightly for 8\u2009weeks. The primary outcome measure was migraine days in weeks 5\u20138 of randomized treatment between melatonin (combined 6\u2009mg\u2009+\u20093\u2009mg) versus placebo. We aimed to enroll\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009210.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study closed early due to slow enrollment (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200972). Two participants were in the single\u2010blind phase when the study closed, therefore the meaningful\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200970. Sixteen percent (11\/70) were lost to follow\u2010up during the single\u2010blind phase. An additional 21% (15\/70) did not meet randomization criteria (&lt;4 headache days:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095, &lt;23\/28 diary days:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097, both:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093). Sixty\u2010three percent (44\/70) were eligible to randomize, of whom 42 randomized (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914 per arm). Taking another preventive at enrollment (OR 8.3, 95% CI 1.01 to 68.9) was the only variable associated with meeting randomization criteria. Of those randomized, 91% (38\/42) provided diary data in the final 4\u2010weeks. However, given the amount of missing data, only those with \u226521\/28 diary days were analyzed\u20147\/14 (50%) in the placebo group, and 20\/28 (71%) in the melatonin groups combined. Median (IQR) migraine\/migrainous days in weeks 5\u20138 of double\u2010blind treatment was 2 (1\u20137) in the placebo group versus 2 (1\u201312) in the melatonin groups combined; the difference in medians (95% CI for the difference) was 0\u2009days (\u22129 to 3). There were no differences in adverse events between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>When compared to recall at enrollment, headache days decreased across the single\u2010blind placebo phase and the double\u2010blind phase. There was no suggestion of superiority of melatonin; however, given the substantial portion of missing data, numerically higher in the placebo arm, and underpowering, this should not be interpreted as proof of inefficacy. Melatonin was generally well tolerated with no serious adverse events. Future migraine preventive trials in this age group may find this trial helpful for anticipating enrollment needs if using a single\u2010blind placebo run\u2010in. Enriching for those already on a migraine preventive may improve randomization rates in future trials, though would change the generalizability of results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14600","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T07:52:41Z","timestamp":1689753161000},"page":"1314-1326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Melatonin for migraine prevention in children and adolescents: A randomized, double\u2010blind, placebo\u2010controlled trial after single\u2010blind placebo lead\u2010in"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0911-7905","authenticated-orcid":false,"given":"Amy A.","family":"Gelfand","sequence":"first","affiliation":[{"name":"Child &amp; Adolescent Headache Program University of California San Francisco  San Francisco California USA"},{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9029-9744","authenticated-orcid":false,"given":"I. Elaine","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Grimes","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-7986","authenticated-orcid":false,"given":"Samantha","family":"Irwin","sequence":"additional","affiliation":[{"name":"Child &amp; Adolescent Headache Program University of California San Francisco  San Francisco California USA"},{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Qubty","sequence":"additional","affiliation":[{"name":"Minneapolis Clinic of Neurology  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin","family":"Greene","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Oregon Health Sciences University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Waung","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Powers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Behavioral Medicine and Clinical Psychology Cincinnati Children's Hospital  Cincinnati Ohio USA"},{"name":"Headache Center Cincinnati Children's Hospital  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Szperka","sequence":"additional","affiliation":[{"name":"Pediatric Headache Program Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610384"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2016-313458"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.0285"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12859"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413485658"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(03)01717-2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2004.00757.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.11.2034"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.26971"},{"key":"e_1_2_11_11_1","volume-title":"Nature's Bounty Triple Strength Quick 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