Clobazam in the treatment of Lennox-Gastaut syndrome.
OBJECTIVE
This randomized, double-blind, dose-ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox-Gastaut syndrome (LGS).


METHODS
Sixty-eight patients with LGS aged 2-26 years were administered CLB (low dose = target 0.25 mg/kg/day; high dose = target 1.0 mg/kg/day). The study consisted of 4-week baseline, 3-week titration, and 4-week maintenance periods, followed by a 3-week taper or continuation in an open-label study. Seizure frequency was recorded in a diary by the parent/caregiver throughout the study.


RESULTS
Weekly drop seizure rates were significantly reduced from baseline in both the high-dose and low-dose groups; the reduction was significantly greater in the high-dose group. A significantly greater proportion of patients in the high-dose group experienced reductions in drop seizures of >or=25%, >or=50%, and >or=75% compared to the low-dose group; more patients in the high-dose group experienced a 100% reduction, but the difference was not significant. Nondrop seizures were also reduced in a dose-dependent manner. In both investigator and parent/caregiver global evaluations, patients in the high-dose group showed significantly greater improvements in overall symptoms compared to low-dose CLB. Adverse events were generally mild or moderate, and were similar between dose groups. Five serious adverse events were reported in four patients, but in no case was CLB discontinued.


CONCLUSIONS
Clobazam was well tolerated and reduced drop seizure rates; high-dose CLB was more effective than low-dose CLB. Other seizure types were also reduced.
Conry
Joan A
JA
Department of Neurology, Children's National Medical Center, Washington, DC 20010, USA. jconry@cnmc.org
Ng
Yu-Tze
YT
Paolicchi
Juliann M
JM
Kernitsky
Lydia
L
Mitchell
Wendy G
WG
Ritter
Frank J
FJ
Collins
Stephen D
SD
Tracy
Katherine
K
Kormany
William N
WN
Abdulnabi
Radhi
R
Riley
Bill
B
Stolle
Julie
J
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D002658:Developmental Disabilities / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam