{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:46:39Z","timestamp":1792806399948,"version":"4.5.0"},"reference-count":100,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007437","name":"TrygFonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007437","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A evaluation of the effect of verapamil and other calcium channel blockers in cluster headache (CH) treatment and an investigation of possible effect mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Verapamil has been used in the prevention of CH for almost 3 decades, however, the mode of action and therapeutic target is still unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Pubmed search was conducted: \u201cVerapamil\u201d[Mesh] and \u201cCluster Headache\u201d[Mesh]. We identified 5 relevant studies for CH. Publications were included if they made a substantial contribution within 3 prespecified areas: Efficacy (randomized controlled\u2010trials or open labels studies), safety, and mechanism of effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Clinical effect<\/jats:italic>\n                      : Clinical preventive treatment of CH with verapamil is based on 2 randomized controlled studies and 3 open\u2010label studies. In total, 183 CH patients participated. Verapamil 360 mg\/day was used in both controlled studies. Half of the chronic patients experienced benefit from verapamil treatment and the attack burden of episodic patients was, on average, reduced by 1 attack\/day. Open\u2010label studies support a dose\u2010dependent level of efficacy.\n                      <jats:italic>Mechanism of effect<\/jats:italic>\n                      : Human and animal studies indicate that verapamil may exert its effect by modulating circadian rhythms, perhaps in central pacemakers, and\/or by affecting release of calcitonin gene\u2010related peptide.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Verapamil appears to be an effective prophylactic drug in the treatment of CH and despite the scarcity of controlled trials, it is still the drug of choice. A chronotherapeutic approach might increase the effect. More basic and pharmacokinetic research is needed before the mechanism can be fully understood.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13603","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T10:11:06Z","timestamp":1563963066000},"page":"1198-1211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives"],"prefix":"10.1111","volume":"59","author":[{"given":"Anja S.","family":"Petersen","sequence":"first","affiliation":[{"name":"Department of Neurology, Danish Headache Center Rigshospitalet\u2010Glostrup Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads C. 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