Abstracts

Rationale: This study was conducted to determine if adjunctive use of verapamil as a P-glycoprotein inhibitor in patients with refractory temporal lobe epilepsy is efficacious in decreasing seizure frequency. We also tried to investigate the safety and tolerability of adjunctive use of verapamil in these patients.Methods: This was an open-label pilot study. Inclusion criteria were: male / female patients, between ages 18 and 65; with temporal lobe epilepsy; with medically-refractory seizures and one or more seizures per month. In the first visit, signing of informed consent, enrollment and registration in the study was done. In the second visit (8-week baseline), seizure type and seizure count was determined. Patients were divided randomly into two groups. Group A received 40 mg three times a day, that was titrated to this dose in a week (n=11) and group B received 80 mg three times a day, which was titrated to the mentioned dose in two weeks (n=9), after confirming the tolerability to the previous dose. All patients were followed for eight weeks after their titration period. The proportion of responders, that is, patients with at least a 50% reduction in seizure (complex partial seizures and generalized tonic-clonic seizures) frequency from baseline, and mean percent reduction in seizure frequency was tabulated. This study was conducted in accordance with local ethical regulations.Results: Twenty patients were included in the analysis. In three patients from group B, we were forced to reduce the dose of verapamil from 240 mg per day to 120 mg per day, because of the intolerable adverse events; they entered into group A. One patient from group A had poor drug adherence and she was excluded from the study. Therefore, there were thirteen patients in group A (120 mg/day) and six patients in group B (240 mg/day). Totally, seven patients (36.84%) reached the responder rate. Three patients (50%) in group B were among the responders; two of these patients achieved seizure freedom and one patient experienced more than 95% seizure reduction. Four patients (30.7%) in group A responded favorably to verapamil. There was no verapamil adverse event that causes permanent drug discontinuation in any of the patients. Transient or mild treatment emergent adverse events were reported by 14 out of the remaining16 patients (87.5%).Conclusions: Developing new means of improving the effectiveness of existing AEDs is a desirable way of tackling the dilemma of medically-refractory epilepsy. Hypothetically, P-gp inhibitors (such as verapamil) might be used to counteract the removal of AEDs from the epileptogenic tissue through excessive expression of multi-drug efflux transporters such as P-glycoprotein (P-gp). Such a strategy was adopted in this study, and we observed a significant achievement in the seizure control in patients with refractory temporal lobe epilepsy in a dose-dependent manner.