Abstracts

Epilepsy in the elderly presents special challenges. Overall, elderly patients tend to be more sensitive to drug effects and often need lower dosages than younger adults. However, recommendations concerning antiepileptic drugs (AEDs) in the elderly are often based on assumptions that they will express the same side effects as younger adults, but amplified in incidence and severity. Yet, few studies have specifically evaluated AEDs in the elderly.
Nearly 100 elderly ([ge]65 yrs) patients have participated in double-blind studies of topiramate (TPM) monotherapy in newly diagnosed epilepsy and have received 50-500 mg/day TPM. Pooled data do not reveal a pattern of increased adverse events (AEs) in elderly vs. younger adults. To evaluate TPM monotherapy in the elderly, a double-blind, dose-comparison study was initiated in patients [ge]60 years of age with partial-onset seizures. Blinded demographic and interim safety data are reported here.
Patients [ge]60 yrs with a confirmed diagnosis of epilepsy characterized by partial-onset seizures, with or without secondary generalization, were eligible if, in the 6 mos before enrollment, they had [ge]1 seizure and [ge]2 seizures in previous 12 mos. Patients could be untreated or receiving 1 AED at study entry. Patients were randomized to double-blind treatment with 50 or 200 mg/day TPM. The 25 mg/day starting dose was increased weekly in 25-mg increments to the assigned target or maximally tolerated dose. The baseline AED was gradually withdrawn once patients reached 50 mg TPM. Patients continued treatment until study end unless TPM was discontinued due to inadequate seizure control, seizure worsening or adverse events. Primary efficacy endpoint is proportion of patients maintained on monotherapy [ge]12 wks.
39 patients have been enrolled; the study remains blinded. Median baseline age: 68 (59-83) yrs. Median baseline seizure frequency: 1/mo (0.3-9.3/mo). Baseline seizure type: simple partial seizures, N=11; complex partial seizures, 19; secondarily generalized seizures, 16; other, 1. To date, 46% of patients have completed the study without withdrawing. Of those withdrawn, 21% discontinued due to inadequate seizure control and 13% due to AEs. AEs occurring in [ge]3 patients (patients could have more than 1 AE): somnolence (5); depression, dizziness, fatigue, headache (4 each); and ataxia, injury, nausea (3 each). Cognitive complaints have been language disorder (N=2); confusion, cognitive problems, memory difficulty, and psychomotor slowing (1 each).
In these elderly patients, AEs are qualitatively consistent with those in other TPM monotherapy studies. The small number of patients with cognitive complaints is particularly encouraging. Somewhat fewer patients (13%) have discontinued due to AEs in our study vs. other TPM monotherapy studies (17% discontinued). Study enrollment continues with a goal of enrolling 80 patients.
[Supported by: Ortho-McNeil Pharmaceutical]