A DOUBLE-BLIND STUDY OF TOPIRAMATE (TPM) MONOTHERAPY IN OLDER PATIENTS WITH PARTIAL-ONSET SEIZURES
Abstract number :
1.332
Submission category :
Year :
2004
Submission ID :
4360
Source :
www.aesnet.org
Presentation date :
12/2/2004 12:00:00 AM
Published date :
Dec 1, 2004, 06:00 AM
Authors :
1R. Eugene Ramsay, 2A. James Rowan, 3Mark Spitz, 4Basim Uthman, 5Joseph I. Sirvin, 6Tim E. Frederick, 7Flavia M. Pryor, and 8Joseph F. Hulihan
Because aging alters pharmacokinetics, antiepileptic drug (AED) profiles, particularly tolerability, may be very different in older adults. We evaluated 50 vs. 200 mg/day TPM as monotherapy in patients [ge]60 yrs old with partial-onset seizures. Patients who were drug-na[iuml]ve or receiving a stable regimen of 1 AED were eligible for double-blind 24-wk study if they had [ge]1 seizure in previous 6 months. TPM was titrated by 25 mg/day per week to target or maximum tolerated dose as the concomitant AED, if any, was withdrawn. 39 patients were randomized to TPM 200 (mean age, 69 yrs); 38 to TPM 50 (68 yrs). Median baseline seizure frequency was 0.3/month in both groups. Median treatment duration was 23 (TPM 200) and 18 wks (TPM 50). With TPM 200, 18 (46%) were maintained [ge]12 wks on monotherapy vs. 13 (34%) with TPM 50; 56% (N=20) and 40% (N=14), respectively, had no seizures during double-blind treatment. Median time to 1st seizure: TPM 200, [gt]168 days; TPM 50, 100 days. Patients reporting [ge]1 AE: TPM 200, N=24 (62%); TPM 50, N=25 (66%). Most common AEs ([ge]10%) for TPM 200: depression, ataxia, injury (N=4 each, 10%); for TPM 50: headache (N=6, 16%), somnolence (N=6, 16%), dizziness (N=5, 13%), fatigue and nervousness (4, 11% each). Memory difficulty and language difficulty were reported by 3 patients each (TPM 200, N=1; TPM 50, N=2); 2 reported nonspecific cognitive problems (1/group) and confusion (1/group); 1 (TPM 50) reported psychomotor slowing. 7 (18%) patients discontinued due to AEs, most commonly with headache (N=4), ataxia (3), somnolence (3), paresthesia (2), dry mouth (2), decreased appetite (2). 200 mg/day was associated with a somewhat longer duration of double-blind treatment, more patients maintained on monotherapy, longer time to 1st seizure and a higher seizure-free rate compared with 50 mg/day, although the difference was not statistically significant. With 50 mg/day TPM, 40% were seizure-free. Few patients reported adverse cognitive effects, despite doses up to 200 mg/day. Overall, 200 mg/day was as well tolerated as 50 mg/day. Results of this pilot study with TPM compare favorably with other double-blind trials of newer AEDs in elderly patients. (Supported by Ortho-McNeil Pharmaceutical)