{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:47:58Z","timestamp":1789274878375,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene\u2013related peptide, has been approved for the preventive treatment of migraine in adults. CM and depression are highly comorbid.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The 12\u2010week, Phase 3 HALO trial randomized patients with CM to fremanezumab quarterly (675\u00a0mg\/placebo\/placebo), fremanezumab monthly (675\/225\/225\u00a0mg), or placebo. Post hoc analyses evaluated the effects of fremanezumab in patients with moderate to severe depression (baseline 9\u2010item Patient Health Questionnaire sum score \u226510) on monthly number of headache days of at least moderate severity; monthly migraine days; Patient Global Impression of Change (PGIC); 6\u2010item Headache Impact Test (HIT\u20106) scores; and depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For the 219\/1121 (19.5%) patients with moderate to severe depression at baseline, fremanezumab was associated with a significant reduction in monthly number of headache days of at least moderate severity for active treatment versus placebo (least\u2010squares mean change\u00a0\u00b1\u00a0standard error for quarterly dosing: \u22125.3\u00a0\u00b1\u00a00.77; for monthly dosing: \u22125.5\u00a0\u00b1\u00a00.72; and for placebo: \u22122.2\u00a0\u00b1\u00a00.81; both\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). More patients achieved a \u226550% reduction in headache days of at least moderate severity with fremanezumab (quarterly: 31\/78 [39.7%]; monthly: 39\/96 [40.6%]) than placebo (9\/67 [13.4%]; both\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Compared with placebo, fremanezumab improved PGIC and HIT\u20106 scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fremanezumab demonstrated efficacy in the preventive treatment of CM and reduced headache impact in patients with comorbid depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14097","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T12:38:24Z","timestamp":1619181504000},"page":"662-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Effects of fremanezumab in patients with chronic migraine and comorbid depression: Subgroup analysis of the randomized HALO CM study"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-2897","authenticated-orcid":false,"given":"Richard B.","family":"Lipton","sequence":"first","affiliation":[{"name":"Department of Neurology Albert Einstein College of Medicine Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Teva Branded Pharmaceutical Products R&amp;D, Inc. West Chester PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Galic","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Teva Pharmaceuticals Europe B.V. Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Seminerio","sequence":"additional","affiliation":[{"name":"North America Medical Affairs Teva Branded Pharmaceutical Products R&amp;D, Inc. West Chester PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul P.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Teva Branded Pharmaceutical Products R&amp;D, Inc. West Chester PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Aycardi","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Teva Branded Pharmaceutical Products R&amp;D, Inc. West Chester PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo E.","family":"Bigal","sequence":"additional","affiliation":[{"name":"Research and Development Teva Branded Pharmaceutical Products R&amp;D, Inc. West Chester PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Bibeau","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Teva Branded Pharmaceutical Products R&amp;D, Inc. 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