Introduction: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy, characterised by multiple seizure types, generalised slow spike-and-wave complexes on the EEG, and cognitive impairment. Seizures in LGS are typically resistant to treatment with antiseizure medications (ASMs). Tonic/atonic (“drop”) seizures are of particular concern, due to their liability to cause physical injury.
Areas covered: We summarise evidence for current and emerging ASMs for the treatment of seizures in LGS. The review focuses on findings from randomised, double-blind, placebo-controlled trials (RDBCTs). For ASMs for which no double-blind trials were identified, lower quality evidence was considered. Novel pharmacological agents currently undergoing investigation for the treatment of LGS are also briefly discussed.
Expert opinion: Evidence from RDBCTs supports the use of cannabidiol, clobazam, felbamate, fenfluramine, lamotrigine, rufinamide, and topiramate as adjunct treatments for drop seizures. Percentage decreases in drop seizure frequency ranged from 68.3% with high-dose clobazam to 14.8% with topiramate. Valproate continues to be considered the first-line treatment, despite the absence of RDBCTs specifically in LGS. Most individuals with LGS will require treatment with multiple ASMs. Treatment decisions should be individualised and take into account adverse effects, comorbidities, general quality of life, and drug interactions, as well as individual efficacy.
Keywords: Antiseizure medication, Cannabidiol, Drop seizure, Epilepsy, Fenfluraminw, Lennox-Gastaut, Pharmacotherapy, Soticlestat