title: High-Dose Verapamil in Episodic and Chronic Cluster Headaches and Cardiac Adverse Events: Is It as Safe as We Think?
abstract: Cluster headache (CH) is a primary headache disorder with relatively effective treatments. Although few sufficiently controlled trials are available, verapamil is recommended as the first-line prophylactic drug for CH by the French Headache Society (with a low level of evidence, level B) and by the EFNS (European Federation of Neurological Societies, level A). Daily doses of more than 480 mg (and up to 1200 mg daily) are frequently used off-label, while 360 mg daily is the only dosage to have demonstrated its effectiveness in a double-blind trial against placebo, and the usual label posology used by cardiologists is 240 mg daily in hypertension. We report the case of a 19-year-old man who was self-reported to our cardiology consultation for dyspnea and asthenia for 18 months. His medical history consisted of CH crisis for 4 years treated by verapamil 720 mg/day for 18 months with relatively good efficiency. His electrocardiogram (ECG) showed a sinus bradycardia at 40 bpm with a first-degree atrio-ventricular block. Evolution was favorable after progressive verapamil discontinuation. Analysis performed on the French Pharmacovigilance Database between July 1, 2000 and December 1, 2014 found four other cases of cardiac adverse events related to high-dose verapamil used in CH prevention (two cases of syncope with complete atrio-ventricular block with verapamil 1200 and 240 mg daily, respectively, one syncope related to sick sinus syndrome with verapamil 360 mg daily, and one case of sinus bradycardia with verapamil 720 mg daily). Although available studies seem to demonstrate an apparent good tolerance, this off-label practice should not be considered as standard of care and requires strict cardiac monitoring, as suggested by the Agence Nationale de Sécurité du Médicament (ANSM) in a recent re-evaluation of the benefit/risk ratio of high-dose verapamil used in CH prevention.
authors.affiliation: Department of Pharmacology, CHU de Caen, Avenue de la côte de nacre, 14000, Caen, France. alexandrej@chu-caen.fr.|Department of Cardiology, CHU de Caen, 14032, Caen, France. alexandrej@chu-caen.fr.|Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, 14032, Caen, France. alexandrej@chu-caen.fr.|Université de Caen Basse-Normandie, Medical School, 14032, Caen, France. alexandrej@chu-caen.fr.
authors.forename: Joachim
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: Department of General Medicine, CHU de Caen, 14032, Caen, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Humbert
authors.affiliation: Department of Pharmacology, CHU de Caen, Avenue de la côte de nacre, 14000, Caen, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Sassier
authors.affiliation: Department of Cardiology, CHU de Caen, 14032, Caen, France.|Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, 14032, Caen, France.|Université de Caen Basse-Normandie, Medical School, 14032, Caen, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Milliez
authors.affiliation: Department of Pharmacology, CHU de Caen, Avenue de la côte de nacre, 14000, Caen, France.|Université de Caen Basse-Normandie, Medical School, 14032, Caen, France.|Université de Caen Basse-Normandie, Inserm U 1075 COMETE, 14032, Caen, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Coquerel
authors.affiliation: Department of Pharmacology, CHU de Caen, Avenue de la côte de nacre, 14000, Caen, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Fedrizzi