Abstracts

RATIONALE: Topiramate has been approved as adjunctive therapy for adults and pediatric patients with partial onset seizures or generalized tonic-clonic seizures. Overall topiramate is well tolerated but has some drug specific side effects such as word finding difficulties which limits its use. Little information exists on the tolerability or efficacy of topiramate in older patients. Concern has been voiced that side effects will be significantly higher in this population and thus may restrict its use in the older patient. This study was undertaken to evaluate the tolerability and efficacy of topiramate in the elderly.
METHODS: This is a 24-week, double-blind randomized, multi-center trial of topiramate in patients 60 years and older. Patients with partial onset epilepsy taking either no AED or on a stable regimen of one AED can be included in the study. To enter the study the patients must have had at least one seizure in the previous six months, two in the prior year and experiencing sufficient side effects to warrant change in therapy. Patients are randomized to one of two target doses (50 mg/day or 200 mg/day). Initial dose is 25 mg/day in both treatment arms and titration is by 25 mg/week until target dose is achieved or toxicity is encountered.
RESULTS: To date, 18 patients have been enrolled. Mean age is 68.8 and 77.7% are males. Prior AED therapy included phenytoin (N=15), carbamazepine (N=4), valproate (N=1), gabapentin (N=1) and phenobarbital (N=1). The average seizure frequency in the 3-month retrospective baseline ranged from 0-5/month. Average seizure frequency on treatment ranged from 0-1/month. Seizure types are 38.9% SPS, 50.0% CPS, 72.2% GTC, and 66.7% mixed. Systemic toxicities reported were weight gain (11.1%)and weight loss (11/1%). Neurotoxicities consisted of dizziness 11.1%, sedation 5.6%, sweating 5.6%. Only 1 patient reported word-finding difficulty transiently. Overall 66.7% reported improvement on patient global evaluation scale. Twelve patients have had reduction in seizure frequency. Of these, 7 patients have become seizure-free. Five patients terminated early. Only 1 patient dropped out due to side effects (dizziness). One patient had uncontrolled seizures; 1 patient was noncompliant; 2 patients withdrew consent. No hematologic nor serum chemistry abnormalities occurred during the study.
CONCLUSIONS: Topiramate in doses of 50 mg and 200 mg was found to be effective and well tolerated in older patients. No significant adverse cognitive effects were encountered.
Support: Ortho-McNeil Pharmaceutical, Inc.