Effectiveness and tolerability of topiramate in the treatment of epilepsy in elderly patients with new onset vs. longer duration epilepsy

Objective: To explore seizure and tolerability outcomes of topiramate (TPM) in mono- or combination therapy in elderly patients with epilepsy with either new onset (NOE) or longer duration epilepsy (LDE).

Methods: Prospective, single arm, multicentre phase IV clinical trial (TOP-GER-13). Patients ≥60 years of age were followed for 12 months. Doses of TPM and concomitant antiepileptic drugs could be adjusted individually. Seizure frequency and adverse events were documented at each visit.

Results: 107 patients (53% male, mean age 69±7 years) were enrolled. NOE (disease duration <1 year) was present in 52 patients with a median baseline seizure frequency of 0.83 (interquartile range (IQR) 0.67–1.83) per 4 weeks. In patients with LDE (≥1 year), median seizure frequency at baseline was 1.33 (IQR 0.67–2.33) per 4 weeks. Differences between groups were non-significant. At endpoint the mean total daily dose on TPM monotherapy was 98mg and 153mg on add-on. During the trial, median seizure frequency per 4 weeks decreased to 0 (IQR 0–0.47) and 0.14 (IQR 0–0.84), respectively (both p<0.0001 versus baseline). Differences in baseline seizure frequency, during the study as well as the absolute change in seizure frequency between groups were non-significant (p>0.05). However, rate of seizure free patients was higher in NOE compared to LDE (59% vs. 29%, p<0.001).

43% had at least one treatment-emergent adverse event (TEAE). TEAEs ≥5% were somnolence (9.4%), dizziness (7.5%), paraesthesia (5.6%), memory disturbance (5.6%) and depression (5.6%).

Conclusion: In elderly patients with epilepsy, TPM was well tolerated and associated with a high number of seizure free patients which was highest among patients with recent onset epilepsy.