Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS).
OBJECTIVE
To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials.


METHODS
This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10-13 and 16-19).


RESULTS
At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3-41.1%; > or =50% responder rate was 40.9-44.2%; and seizure freedom rate was 15.0-15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%).


CONCLUSIONS
Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated.
Dupont
S
S
Unité d'Epilepsie, Clinique Neurologique, Hôpital de la Pitié-Salpêtrière, APHP, UPMC, Paris, France. sophie.dupont@psl.ap-hop-paris.fr
Striano
S
S
Trinka
E
E
Springub
J
J
Giallonardo
A T
AT
Smith
P
P
Ellis
S
S
Yeates
A
A
Baker
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000627:therapeutic use*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D007391:International Cooperation; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide