Abstracts

RATIONALE: Topiramate (TPM) is a novel anticonvulsant drug that has been approved as adjunctive therapy for patients with partial onset seizures and/or generalized tonic-clonic seizures. The side effect profile of this drug in monotherapy is favorable, and drug interactions appear to be few. Little is known about the optimal therapeutic approach for older patients with seizures. The increased hazards of seizures, comorbid conditions, polypharmacy, altered metabolism and compliance argue for the need for safe, effective AED in the elderly population. Although little information exists on the tolerability and efficacy of TPM in older patients, TPM has several characteristics that suggest it may be a useful drug in this patient population.
METHODS: This is a 24-week, blinded, randomized, multi-center trial of TPM in patients 60 and older diagnosed with epilepsy. Patients newly diagnosed as well as those with a history of partial seizures are eligible to participate. Patients taking either no AED or on a stable regimen of one AED who are not controlled can be included. Eligible patients must have had at least one seizure in the previous six months, two in the prior year and have experienced sufficient side effects to warrant change in therapy. Patients are randomized to one of two target doses (50 mg/day or 200 mg/day).The current AED is tapered off and discontinued. 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. The At the end of the 24-wk blinded phase, patients may enter a 4-month open-label phase.
RESULTS: Thirty-four patients have been enrolled in Miami. Mean age is 68.6 and 73.5% are males. 5 patients were new onset. Prior AED therapy included PHT (N=25), CBZ (N=7), PB (N=3), LTG (N=3), VPA (N=2) and GBP (N=2). The average seizure frequency in the 6-month retrospective baseline ranged from 0-3/month. Average seizure frequency on treatment ranged from 0-1/month. Seizure types are 33.3% SPS, 38.2% CPS, 70.6% GTC, and 35.3% mixed. Of the 5 new onset patients only two completed the study and were seizure free. 21 patients have had reduction in seizure frequency. Of those who completed the blinded phase (n = 17), 9 (41.2%) became seizure-free. 61.8% reported overall improvement on patient global evaluation scale. Systemic toxicities reported were weight loss greater than or equal to 2 lbs (38.2%) and weight gain (2.9%). Neurotoxicities consisted of dizziness 2.9%, confusion 5.9%, sweating 2.9%. Only 1 patient reported word-finding difficulty. 14 patients were early terminators. Of these, only 3 exited due to side effects (one patient c/o dizziness and confusion and two patients c/o weight loss). Average weight loss for these 2 patients was 10 lbs. 4 patients had uncontrolled seizures; 2 were noncompliant; and 4 voluntarily withdrew from the trial. No hematologic nor serum chemistry abnormalities occurred during the study.
CONCLUSIONS: TPM has been found to be effective and well tolerated in older adults with epilepsy. TPM as monotherapy in the treatment of seizures in the elderly is promising. Adverse cognitive effects were infrequently encountered at the doses of 50 mg and 200 mg. There were no reports of renal stones in these patients.
[Supported by: Ortho-McNeil Pharmaceutical, Inc.]