Abstracts

Rationale: Rational polytherapy in the treatment of epilepsy is still a controversial topic due to lack of significant evidence. Combination of antiepileptic drugs (AEDs) with different mechanisms of action appears superior to combining those possessing the same similar cellular effects. Clobazam associated with a sodium blocker has been considered an effective combination for treatment of focal seizures. The main objective of this retrospective study was further exploration of the effectiveness and tolerance development of clobazam used as adjunctive therapy to sodium blocker AEDs in the long-term treatment of refractory focal seizures. Methods: We followed the state of 47consecutive patients with focal seizures refractory to maximum tolerated doses of a first-line sodium blocker (35 carbamazepine, 6 oxcarbazepine, 5 phenytoin, 1 lamotrigine) who had clobazam as add-on therapy (doses 5-60 mg/day; mean at the end of follow-up 17.95) for up to 4 years (mean 2.7). Seizure reduction greater than 50% was considered improvement. To measure the tolerance rate, we considered only those who had come to all the consultations along 4 years of follow-up (21 patients). Results: By the end of the 3rd month, 46 patients were seen and 39.13% of them were seizure-free; 13.04% improved 75% to 99%; 17.39%, 50 to 74% and 19.56% did not respond at all. Mean doses of clobazam was 9.57 mg/day. After 6 months, among 39 patients, 48.72% were seizure-free, 20.51% maintained improved state, 30.76% relapsed (mean doses: 10.75). By the end of one year, among 38 patients, 34.21% were seizure-free, 34.21% maintained improved state, 31.58% relapsed (mean doses: 14.47). After two years, among 34 patients, 52.94% were seizure-free, 17.64% improved, 29.41% relapsed (mean doses: 19.45). After three years, among 27 patients, 37.03% were seizure free, 29.62% improved and 25.92% relapsed (mean doses: 20.56). Finally, out of 22 followed for four years,13 (51.1%) remained seizure free after clobazam introduction, 22.72% improved and 18.18% relapsed (mean doses: 17.95). The tolerance rate could be estimated in 21 patients with regular follow-up for four years as follows: 28.57% at the end of the 3^rd month, 42.85% after 6 months, 47.61% after 12 months, 52.38% after 2 years. After 2 years of follow-up there was no increase in the number of patients who were tolerant to the antiepileptic effects of clobazam. Three of these 21 patients have been seizure free since they have started responding to clobazam. Seizure control was achieved up to 6 months after its introduction. Conclusions: Our results are aligned to previous studies that have shown the effectiveness of clobazam as add-on therapy for focal epilepsy. Unfortunately, this AED lost its effectiveness in a long-term follow-up in the majority of the patients evaluated. However, patients who were responsive to this AED after 2 years had no further development of tolerance to its antiepileptic effects.