IntroductionLennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterised by treatment-refractory seizures, including tonic/atonic "drop" seizures, and intellectual impairment and slow spike-wave discharges on the electroencephalogram. Fenfluramine, previously prescribed as a weight-loss drug but then withdrawn, has recently been approved in the US, EU and UK for the adjunct treatment of seizures associated with LGS.Areas coveredEfficacy and safety findings from clinical trials of fenfluramine in LGS are reviewed. The evidence for adverse effects that may be of particular concern with fenfluramine, namely cardiac abnormalities and weight loss, are discussed in the context of the use of fenfluramine for the treatment of the refractory seizures in LGS.Expert opinionFenfluramine has demonstrated efficacy in reducing the frequency of seizures in LGS, notably drop seizures, in short-term and long-term clinical trials. Valvular heart disease and pulmonary hypertension have not been reported at the low doses (≤ 26 mg/day) used in these studies, however, data are limited. Due to its novel mechanism of action, fenfluramine may be of benefit in LGS which has not responded adequately to other antiseizure medications. However, none of these medications, including fenfluramine, achieves the ultimate goal of seizure freedom in most cases.<br/
