Efficacy of Low-Dose Fenfluramine on Adult Patients With Lennox-Gastaut Syndrome

Abstract

Purpose Fenfluramine has received approval for treating seizures in individuals with Lennox-Gastaut syndrome (LGS). Nonetheless, Phase III trials mainly focused on children, leaving limited information regarding its effectiveness and safety in adults. This case series aimed to elucidate these factors in adult patients. Methods This case series examined the clinical progression of adult patients diagnosed with LGS who received fenfluramine at our clinic following its approval in Japan in March 2024, extending through February 2025. Fenfluramine was administered to those experiencing drop attacks and generalized slow spike-and-wave complexes, fulfilling the conventional diagnostic criteria for LGS, and their responses to treatment were analyzed. Results This case series involved nine adult patients aged 18-49. All patients demonstrated efficacy, with seven (78%) experiencing at least a 50% reduction in seizure frequency. No one needed maintenance doses above the recommended starting minimum of 0.2 mg/kg/day, and five patients (56%) achieved seizure control with even lower doses. Remarkably, three patients who did not meet the latest 2022 diagnostic criteria also demonstrated positive responses. Adverse events were reported in five patients (56%), primarily including somnolence, diarrhea, and anorexia. In these situations, a dose reduction to half was necessary, yet efficacy was maintained. Conclusion Low-dose fenfluramine may effectively manage seizures in adult patients with LGS while reducing adverse effects. This case series provides a growing body of real-world data regarding the use of fenfluramine in this patient population.

Keywords: adult; fenfluramine; lennox-gastaut syndrome; low-dose; sigma-1.

Figure 1. EEG showing slow spike-and-wave complexes in Case 3.

Figure 2. EEG showing generalized paroxysmal fast activity in Case 5.