Clobazam in the treatment of Lennox‐Gastaut syndrome

Abstract

and yyOvation Pharmaceuticals, Inc., Deerfield, Illinois, U.S.A. SUMMARYPurpose: This randomized, double-blind, doseranging 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 ‡25%, ‡50%, and ‡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. KEY WORDS: Childhood epilepsy, Drop seizure, Atonic seizure, Akinetic seizure, Catastrophic epilepsy.Lennox-Gastaut syndrome (LGS) is a catastrophic childhood epilepsy characterized by multiple types of seizures and developmental delay. Onset of LGS usually occurs between 3 and 10 years of age, and affects boys more often than girls (Beaumanoir & Dravet, 1992). Typical LGS is described by the presence of the characteristic triad of: (1) tonic axial, atonic, and/or atypical absence seizures; (2) electroencephalography (EEG) abnormalities with bursts of diffuse slow spike-wave pattern of 1.5-2.5 Hz; and (3) impaired intellectual growth (Beaumanoir & Blume, 2002;Crumrine, 2002). Atonic or drop seizures are frequent in LGS and are responsible for most injuries associated with falls. The prognosis for LGS is poor, since the seizures tend to be medically refractory, with only 10% of cases experiencing full seizure remission with available therapies. Most patients experience ongoing cognitive impairment and refractory epilepsy, and some patients experience frequent episodes of status epilepticus (Crumrine, 2002;Markand, 2003 (Markand, 2003).Clobazam (CLB) is a novel 1,5-benzodiazepine that was initially developed as an antianxiety treatment designed to decrease AEs associated with 1,4-benzodiazepines while maintaining efficacy (Chapman et al., 1...

Lennox-Gastaut sendromlu hastaların klinik özellikleri ve uzun süreli seyri

“…In children with Lennox-Gastaut syndrome, lamotrigine and topiramate is efficient in atonic and tonic clonic seizures and valproic acid is efficient in drop attack, atypical absence and myoclonic seizures (19)(20)(21). In studies performed in patients with Lennox-Gastaut syndrome, it has been reported that clobazamine leads to sedation with a lower rate, decreases seizures by 50-100% in more than 50% of the patients, maintains its efficiency of 42% after more than one year of use and provides seizure-free state for more than 6 months in 72% of the patients (22,23). It is reported that seizures of the patients with LGS are decreased with intravenous gammaglubulin treatment (24).…”

Treating patients with medically resistant epilepsy

“…He is a candidate for palliative therapy with vagal nerve stimulation (VNS) 26 and also may benefit from clobazam therapy. 27,28 He may also cooperate with treatment with the ketogenic/Atkins diet. 29 An anterior (66% to 80%) corpus callosotomy is also a good option, and offers the greatest chance for substantial reduction in seizure frequency, especially for the tonic and atonic seizures, though it also has the highest morbidity of the treatments mentioned.…”

Clinical and Encephalographic Changes at Lennox–gastaut Syndrome

“…Лечение осуществляется с применением полите-рапии антиэпилептическими препаратами в макси-мально переносимых дозах [8,23,42,43]. Исходя из нашей практики, оптимальные комбинации в ле-чении СЛГ -вальпроаты + топирамат + сукцинимиды или бензодиазепины (клобазам).…”