The optimum treatment for Lennox-Gastaut syndrome has yet to be established. Lennox-Gastaut syndrome is a seizure (epilepsy) disorder that is commonly associated with behavioural and mental health problems. Many different treatments are currently used in the treatment of this disorder and many more have been tried in the past, often with little success. The review of trials found that there was no evidence to suggest that any one drug was more effective than another in the treatment of this disorder in terms of controlling the different seizure types. More research is needed to compare the therapies currently available.
"This syndrome is characterized by various types of epileptic seizures (mainly tonic seizures), diffuse slow spike-andwave complex patterns on electroencephalogram (EEG), and impairment of cognitive function (Arzimanoglou et al., 2009; Beaumanoir, 1985). The long-term mental and seizure prognoses are generally devastating (Arzimanoglou et al., 2009; Beaumanoir, 1985; Blatter-Arifi, 1991; Oguni et al., 1996; Ohtsuka et al., 1990; Yagi, 1996), and appropriate and early intervention is crucial for the treatment of patients with LGS to prevent mental deterioration. However, therapeutic evidence for antiepileptic drugs (AEDs) in LGS treatment is not sufficiently established due to its complex symptoms and low prevalence rate (less than 1.0 per 10,000 population) (Cowan et al., 1989; Eriksson and Koivikko, 1997; Oka et al., 2006; Olafsson and Hauser, 1999), though several randomized controlled clinical trials have been conducted with some AEDs: felbamate (The Felbamate Study Group in Lennox—Gastaut Syndrome, 1993), lamotrigine (Motte et al., 1997), topiramate (Sachdeo et al., 1999), and clobazam (Ng et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: Purpose
To evaluate the efficacy, safety, and pharmacokinetics of rufinamide as an adjunctive therapy for patients with Lennox–Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial.
We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to rufinamide or placebo. The primary efficacy variable was the percent change in the tonic-atonic seizure frequency per 28 days.
Key findings: Of the 59 patients, 29 were randomized to the rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the rufinamide group than in the placebo group; the median percent change in frequency of tonic-atonic seizures was -24.2% and -3.3%, respectively, (p = 0.003) and that of total seizures was -32.9% and -3.1%, respectively (p <0.001). Subgroup analyses indicated that the efficacy of rufinamide was consistent independent of clinical background characteristics. The common treatment-related adverse events in the rufinamide group were decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%). Transient seizure aggravations were observed in 13 (22.0%) of the 59 patients, though a causal relationship with rufinamide was suspected in only one patient. All adverse events were mild to moderate in severity. The mean plasma concentration of rufinamide within 12 hours after administration was 17.2 μg/mL.
Significance: The present results showed a favorable risk-benefit profile for rufinamide as an adjunctive therapy for patients with LGS.
Epilepsy Research 09/2014; 108(9). DOI:10.1016/j.eplepsyres.2014.08.019 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary generalized tonic-clonic seizures are one of a number of generalized seizure types which also includes absence, myoclonic and atonic seizures. Effective control of tonic-clonic seizures is required to reduce the risk of injury and death and to improve quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not and usually take a combination of antiepileptic drugs.
To assess the effectiveness of adjunctive lamotrigine for refractory primary generalized tonic-clonic seizures.
We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (Ovid) 1950 to June 2010. No language restrictions were imposed. We also contacted GlaxoSmithKline, manufacturers of lamotrigine.
Randomised parallel or cross-over add-on trials of add-on lamotrigine for refractory primary generalized tonic-clonic seizures.
Outcome measures were: proportion of people (1) with 50% or greater reduction in frequency; (2) with cessation of seizures; (3) who had treatment withdrawn; (4) with adverse effects; and (5) cognitive effects; (6) quality of life outcome measures. Data were independently extracted by review authors.
Two small trials were found that met the inclusion criteria. Due to differences in study design we decided not to undertake a meta-analysis. One placebo controlled cross-over trial (26 participants) showed a significant 50% reduction in tonic-clonic seizure frequency with lamotrigine. Rash was the only adverse effect causing discontinuation (N = 7). A placebo controlled parallel trial comparing 117 participants found a significant median percent reduction in tonic-clonic seizure frequency of 66.5% with lamotrigine compared with 34.2% with placebo (P = 0.006). The most common adverse events were dizziness, somnolence and nausea.
Two short term trials indicate that lamotrigine has efficacy against primary generalized tonic-clonic seizures; however, this evidence is insufficient to inform clinical practice and longer term active controlled trials are required.
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