Short-term efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: a multicenter open-label single-arm trial in Korean patients.
OBJECTIVE
To evaluate the efficacy and safety of adjunctive zonisamide (ZNS) therapy in Korean adults with uncontrolled partial epilepsy.


METHODS
Study patients had an average of at least one seizure per 4-week (averaged over a 12-week historical baseline) despite the use of one to three antiepileptic drugs. The starting dose of ZNS was 100mg/day, and was increased to 200mg/day after 2weeks. During the 12-week maintenance period, the dose of ZNS was adjusted to 200-400mg/day based on the physicians' discretion. The global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated.


RESULTS
A total of 121 patients were enrolled, of which 88 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 59.0%. The ≥50% and ≥75% responder rates were 57.3% and 38.5%, respectively. Seizure freedom over the treatment period was observed in 25 patients, but seizure freedom throughout the 16-week treatment period was attained in only 16 patients. On investigator's GES, 84 patients were considered improved, with 33 patients showing marked improvement. In QOLIE-31 scale, seizure worry improved significantly but emotional well-being deteriorated. Treatment-emergent adverse events (AEs) were reported in 80 patients. The most common AEs were dizziness (28.1%), somnolence (24.0%), anorexia (18.2%), headache (14.0%), nausea (13.2%), and weight loss (10.7%). Twenty-two patients discontinued the trial due to drug-related AEs.


CONCLUSIONS
Our results suggest that adjunctive ZNS therapy for the treatment of refractory partial epilepsy, though efficacious, is associated with significant tolerability problems.
Department of Neurology, Severance Hospital, Seoul, Republic of Korea.
Kyoung
K
Heo
Byung In
BI
Lee
Sang Do
SD
Yi
Yong Won
YW
Cho
Dong Jin
DJ
Shin
Hong Ki
HK
Song
Ok Joon
OJ
Kim
Sung-Pa
SP
Park
Sung Eun
SE
Kim
Sang Ho
SH
Kim
Jun Hong
JH
Lee
Kyu-Sik
KS
Kim
Se-Jin
SJ
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007723:Korea; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000188:drug therapy*; D055815:Young Adult; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide