Efficacy and safety of levetiracetam (up to 2000 mg/day) in Taiwanese patients with refractory partial seizures: a multicenter, randomized, double-blind, placebo-controlled study.
OBJECTIVE
To assess the efficacy and safety of adjunctive levetiracetam (LEV) therapy in controlling partial-onset seizures refractory to other antiepileptic drugs (AEDs) in a multicenter study in Taiwanese adults.


METHODS
Ninety-four patients aged 16-60 years with refractory partial seizures were randomized to receive LEV (n = 47) or placebo (47) for 14 weeks and composed the intention-to-treat (ITT) population. After the first 2 weeks, LEV patients had their dosage increased from 500 mg twice daily to 1,000 mg twice daily. A 12-week maintenance phase followed, after which patients switched to long-term, open-label LEV therapy or entered a 4-week phase of medication discontinuation.


RESULTS
All patients from the ITT population, except one LEV-treated patient with missing seizure-count data, were included in the primary efficacy analysis. The least square mean of logarithmically transformed weekly partial-seizure frequency was significantly lower in the LEV than in the placebo group (0.813 vs. 1.085; p = 0.001). LEV reduced log-transformed weekly partial-seizure frequency by 23.8% (95% confidence interval, 10.4-35.2%) relative to placebo. Significantly more LEV than placebo patients (43.5% vs. 10.6%) experienced a response of a >or=50% decrease from baseline in weekly frequency of partial seizures [odds ratio, 6.5 (95% CI, 2.2-19.3); p < 0.001]. Adverse events were reported in 34 (72.3%) of 47 LEV-treated patients and 32 (68.1%) of 47 placebo patients. The three most common adverse events in the LEV and placebo groups were somnolence (40.4% and 14.9%), dizziness (14.9% and 8.5%), and headache (10.6% and 8.5%), respectively. Only four patients (three LEV-treated patients and one placebo patient) were withdrawn from the study because of adverse events.


CONCLUSIONS
Adjunctive LEV therapy, <or=1,000 mg twice daily, was significantly more effective than placebo and was generally well tolerated in Taiwanese adults with treatment-resistant partial-onset seizures.
Tsai
Jing-Jane
JJ
Department of Neurology, National Cheng Kung University Hospital and Medical College of National Cheng Kung University, Tainan, Taiwan.
Yen
Der-Jen
DJ
Hsih
Mo-Song
MS
Chen
Shung-Sheng
SS
Hiersemenzel
Reinhard
R
Edrich
Pascal
P
Lai
Chi-Wan
CW
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D018592:Cross-Over Studies; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D012893:Sleep Wake Disorders / Q000139:chemically induced; D013624:Taiwan / Q000208:ethnology; D016896:Treatment Outcome
D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam