Effectiveness of topiramate in patients with epilepsy transitioning from valproic acid – results of an open-label, non-interventional trial

Objective: To evaluate seizure frequency and tolerability in patients with epilepsy treated with topiramate (TPM, Topamax®) transitioning from valproic acid (VPA).

Methods: Multicenter open-label non-interventional trial (TOPMAT-EPY-403) following patients ≥12 years of age with epilepsy previously unsuccessfully treated with VPA. Patients were prospectively followed for 20 weeks after transitioning to TPM. A 12-week retrospective seizure frequency was used as baseline.

Results: 147 patients (59% female; mean age 42yrs (±SD 19)) were followed. Median duration of epilepsy was 9yrs (range, 0–60yrs). 77% had seizures during the 12-week retrospective baseline. Most frequent seizure types at baseline were generalized tonic-clonic (52%), complex partial (23%), and simple partial (12%). Main reasons for transition from VPA to TPM were insufficient efficacy (61%) and/or side effects (81%). Mean dose of VPA at time of first administration of TPM was 1286±629mg. Median TPM dose was 125mg/day at endpoint. Mean (±SD) seizure frequency decreased significantly from 32±248 seizures per month during the retrospective baseline to 3±16 seizures/month during the maintenance period (p<0.001). The responder rate (≥50% seizure reduction) during the last three months of observation was 75%, and 51% patients remained seizure-free during this period. 16% of patients discontinued TPM, 8% due to an adverse event (AE), and 3% due to insufficient efficacy. Treatment-emergent adverse events (TEAE) were reported in 14% of patients. TEAE occurring in ≥3% were paraesthesia (4%) and weight decrease (5%). 70% of patients were on TPM monotherapy at endpoint and 77% continued TPM therapy.

Conclusion: In patients previously unsuccessfully treated with VPA, topiramate was well tolerated and was associated with a substantial reduction in seizure frequency and a high seizure-free rate.