Effectiveness of topiramate across age groups in elderly patients with epilepsy – results of an open-label, phase IV clinical trial
Objective: To assess effectiveness of topiramate (Topamax®, TPM) in different age groups of elderly patients (≥60) with epilepsy.
Methods: In this prospective, open label, multicenter phase IV flexible dose clinical trial (TOP-GER-13), elderly patients (60–64, 65–74 and ≥75 years with epilepsy irrespective of seizure type were included and followed for a median of 12 months. Doses of TPM and concomitant AEDs could be adjusted individually. Seizure frequency and adverse events were assessed at each visit.
Results: 107 patients (53% male, mean age 69±7 years) were enrolled encompassing 32 patients 60–64 years, 54 patients 65–74 years and 21 patients ≥75 years. 102 patients had at least one seizure during the retrospective 12-week baseline. Mean duration of epilepsy was 11.8, 9.7 and 5.5 years, respectively. Most frequent seizure types at baseline were generalized tonic-clonic (58%) and complex partial (25%) with the highest seizure frequency in the oldest group (9.3±34.1at baseline). Mean seizure frequency for all was 3.5±14.6at baseline and decreased to 1.6±7.7at endpoint (p<0.0001). At endpoint, the mean TPM dose given as monotherapy was 98mg/day and 153mg/day if given adjunctively. Mean monotherapy dose was lowest in the oldest elderly group (86mg/day) and the percentage of monotherapy was highest in the oldest group. The proportion of responders (seizure reduction ≥50%) was highest in the youngest group (87% responders), and overall, 78% of patients were responders and 44% remained seizure-free throughout the study.
46 patients (43%) had at least one treatment-emergent adverse event (TEAE). The number of TEAEs was highest amongst the oldest elderly. TEAEs ≥5% were somnolence (9.4%), dizziness (7.5%), paraesthesia (5.6%), and memory difficulties 5.6%. Main reasons for study discontinuation (40% overall) were an TEAE (15.9%) or loss to follow-up (12.2%).
Conclusion: In elderly patients with epilepsy, TPM was well tolerated amongst all age groups, was associated with a significant decrease in seizure frequency, and was well tolerated. Doses used were slightly lower than the recommended target doses for adults.