Page 104 - Migraine, the heart and the brain

Chapter 6
headache treated with verapamil. No consensus was reached on EKG monitoring during verapamil treatment and dose adjustments. For verapamil doses of ≥ 480 mg/ day, half the panel advised ambulatory EKG Holter-monitor registration. Consensus about absolute and relative contraindications for continuing HDV largely followed FDA recommendations. There was no preference among the panel members for either sustained- or regular-released formulations of verapamil.
Although cardiac arrhythmias and bradycardia have been reported in up to 40% of patients using HDV,7,8 published recommendations on EKG monitoring are remarkably limited, highly variable, and solely based on expert opinions.2,5,9,10 The protocols range from: (i) starting with 240 mg verapamil daily after pretreatment EKG and increasing the dose with 80 mg every two weeks, each time preceded by an EKG, until attacks have subsided, or side effects have become too serious, or a maximum dose of 960 mg/day is reached11 to (ii) starting with a pretreatment EKG (without speci ed starting dose and titration scheme) followed by (a) repeated EKGs before and 10 days after each dose increase3; (b) repeated EKGs only at doses above 480 mg/ day12; or (c) repeated EKGs with each dose increase (without specifying whether this is before or after dose increase) and every three months when on a stable dose13.
The recommendations of the panel members were similarly divergent. They only reached consensus about performing a pretreatment EKG and near consensus about that pretreatment EKG was not necessary in patients who had not experienced cardiac adverse events during a previous cluster period treated with verapamil. No consensus was reached on EKG monitoring during treatment and around dose adjustments. Most panel members, however, did recommend repeated EKG ve days after each verapamil dose increase, in line with the time it takes to reach steady state plasma levels after increasing the dose. 4 Interestingly, half the panel members recommended Holter EKG for doses > 480 mg/day, which is not mentioned in any cluster headache treatment review or guideline.
FDA considers second and third degree AV block, sick-sinus syndrome without pacemaker, and atrial flutter/ brillation with accessory bypass tract hard contra- indications for use of verapamil. Panel members felt that a 2nd degree AV block Wenckebach type only is a relative contra-indication and did not reach consensus about whether sick sinus syndrome and atrial flutter/ brillation were absolute contraindications.
Verapamil is available in regular or extended release formulations with different time-to-peak-concentrations and half-life times.4 The three available ef cacy studies on verapamil in cluster headache were conducted with either sustained,9 regular
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