A pilot double-blind trial using verapamil as adjuvant therapy for refractory seizures

Rationale: Given verapamil's property as a glycoprotein inhibitor, this drug could increase the effective concentration of antiepileptic drugs (AEDs) in the epileptic foci, reducing the number of seizures. This pilot study was designed to evaluate the safety and efficacy of verapamil as adjunct therapy in pharmacoresistant patients with focal onset seizures. Methods: This was a single-centered, randomized, double-blind and placebo-controlled trial evaluating verapamil as an add-on therapy for adult patients with refractory epilepsy. Results: Twenty-two patients were randomized, but five of them withdrew and one patient passed away after consent, having no exposure to either verapamil or placebo; four patients withdrew during or after the double-blind phase due to side effects. From these four patients, only one patient was in the verapamil group. Twelve patients (59%) finished the study. Some patients experienced lower seizure frequencies, but none of them reached 50% reduction. In addition, there was no statistically significant decrease in the seizure frequency of patients receiving verapamil. When comparing the verapamil with the placebo at the double-blind or the open label study phases, the average difference in seizure range also failed to show significance (p=0.41 and p=0.98, respectively). No significant cardiovascular effects were observed, and side effects unique to verapamil were skin rashes and feet edema. Throughout the study, carbamazepine, valproic acid and clobazam levels increased following verapamil intake; minor dosage adjustment was required in one patient on carbamazepine. Conclusions: This pilot study has shown mild benefits of verapamil use in comparison to placebo as an add-on therapy for a group of non-selected patients with refractory epilepsy. A partial response in a subset of patients was seen. No significant safety problems happened, but adjustments on AEDs may be required during verapamil use. (C) 2014 Elsevier B.V. All rights reserved.