Substitution has better efficacy than add-on therapy for patients with focal epilepsy after their first antiepileptic drug treatments fail.

Purpose: This study is to compare the efficacy of substitution with add-on therapy in patients with focal epilepsy, whose first monotherapy has failed after receiving usual treatments.

Methods: This is a prospective, long-term, non-randomized observational cohort study. Data were collected from Wenzhou Epilepsy Follow Up Registry Database. Focal epilepsy patients from January 2003 to June 2015, whose first monotherapy had failed, were registered. The total observation period was three years. The major outcome measure was seizure remission rate. The secondary outcome measures included retention rates and incidences of intolerable adverse events.

Results: A total of 596 patients were included, among them 209 received substitution therapy, and 387 received add-on therapy. Seizure remission rates were 56.5% by substitution therapy and 39.0% by add-on therapy, respectively (p = 0.025). Retention rate was 49.3% by substitution therapy, and 36.2% by add-on therapy (p = 0.031). Incidence of intolerable adverse events for substitution and add-on was 4.8% and 7.2%, respectively (p = 0.243). There were 457 patients who failed to the first monotherapy due to lack of efficacy. In these patients, seizure remission rates of substitution and add-on were 51.0% and 38.1%, respectively (p = 0.171). Retention rates were 48.1% and 36.0%, respectively (p = 0.136). And, incidences of intolerable adverse events were 2.9% and 6.8%, respectively (p = 0.137).

Conclusion: The seizure remission rate and retention rate of substitution therapy are better than those of add-on therapy for focal epilepsy patients whose first monotherapy fails.