Anja S Petersen1, Mads C J Barloese1,2, Agneta Snoer1, Anne Mette S Soerensen3, Rigmor H Jensen1. 1. Department of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, Glostrup, Denmark. 2. Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging, Hvidovre Hospital, Hvidovre, Denmark. 3. Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Abstract
OBJECTIVE: A evaluation of the effect of verapamil and other calcium channel blockers in cluster headache (CH) treatment and an investigation of possible effect mechanisms. BACKGROUND: Verapamil has been used in the prevention of CH for almost 3 decades, however, the mode of action and therapeutic target is still unknown. METHODS: A Pubmed search was conducted: "Verapamil"[Mesh] and "Cluster Headache"[Mesh]. We identified 5 relevant studies for CH. Publications were included if they made a substantial contribution within 3 prespecified areas: Efficacy (randomized controlled-trials or open labels studies), safety, and mechanism of effect. RESULTS: Clinical effect: Clinical preventive treatment of CH with verapamil is based on 2 randomized controlled studies and 3 open-label 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-label studies support a dose-dependent level of efficacy. Mechanism of effect: 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-related peptide. CONCLUSION: 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.
OBJECTIVE: A evaluation of the effect of verapamil and other calcium channel blockers in cluster headache (CH) treatment and an investigation of possible effect mechanisms. BACKGROUND:Verapamil has been used in the prevention of CH for almost 3 decades, however, the mode of action and therapeutic target is still unknown. METHODS: A Pubmed search was conducted: "Verapamil"[Mesh] and "Cluster Headache"[Mesh]. We identified 5 relevant studies for CH. Publications were included if they made a substantial contribution within 3 prespecified areas: Efficacy (randomized controlled-trials or open labels studies), safety, and mechanism of effect. RESULTS: Clinical effect: Clinical preventive treatment of CH with verapamil is based on 2 randomized controlled studies and 3 open-label 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 episodicpatients was, on average, reduced by 1 attack/day. Open-label studies support a dose-dependent level of efficacy. Mechanism of effect: 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-related peptide. CONCLUSION: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.