Efficacy and safety of levetiracetam 1000-3000 mg/day in patients with refractory partial-onset seizures: a multicenter, open-label single-arm study.
OBJECTIVE
To evaluate the efficacy and tolerability of levetiracetam as add-on therapy in patients with refractory partial-onset seizures in a protocol designed to reflect clinical practice.


METHODS
All patients in this open-label, single-arm study entered an 8-week baseline period followed by a 4-week titration period and a 12-week maintenance period. Patients initially received levetiracetam 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of levetiracetam could not be increased but could be decreased once if tolerability warranted. Seizure count and adverse events were recorded by patients in a diary. Quality of life and global evaluation of disease evolution were also evaluated.


RESULTS
Ninety-nine patients were enrolled and 91 completed the study. A steady dose was maintained over the last 8 weeks of treatment or longer in 84 patients, with 89.3% of these patients receiving 3000 mg/day, 9.5% receiving 2000 mg/day, and 1.2% receiving 1000 mg/day. A 35.9% median percent reduction from baseline in weekly frequency of partial-onset seizures was observed over the entire treatment period. The median partial-onset seizure count decreased from 2.3 per week during the baseline period to 1.3 per week over the treatment period. A total of 42.4% of patients were responders (> or = 50% reduction from baseline in weekly seizure frequency) over the treatment period; two patients were seizure-free from the first day of treatment throughout the treatment period. The most frequent drug-related adverse events were fatigue (27.3% of patients), somnolence (11.1%), headache (8.1%), and dizziness (8.1%).


CONCLUSIONS
Levetiracetam as add-on therapy at doses up to 3000 mg/day effectively reduced the frequency of partial-onset seizures in patients with refractory epilepsy and was well-tolerated in this study, bridging conditions of placebo-controlled clinical trials and clinical practice.
Beran
Roy G
RG
Strategic Health Evaluators and University of New South Wales, 12 Thomas Street, Suite 5, 6th Floor, Chatswood, NSW 2067, Australia. roy.beran@unsw.edu.au
Berkovic
Samuel F
SF
Black
Andrew B
AB
Danta
Gytis
G
Hiersemenzel
Reinhard
R
Schapel
Graham J
GJ
Vajda
Frank J E
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D011788:Quality of Life; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam