Effect of Fenfluramine on Generalized Tonic–Clonic Seizures in Rare Epilepsy Syndromes: A Review of Published Studies

Background/Purpose: We aim to describe the effectiveness of fenfluramine (FFA) on generalized tonic–clonic seizures (GTCS) or tonic–clonic seizures (TCS) in patients with rare epilepsy syndromes.

Methods: Reports of patients treated with FFA for seizures associated with rare epilepsy syndromes were identified and included if FFA was used for convulsive seizure control. The studies selected described a change in the frequency of GTCS, TCS, or major motor seizures. Case reports or studies where the reduction in GTCS or TCS was unclear were excluded. Initial FFA doses, duration of treatment (exposure), and reduction in GTCS/TCS are reported. Descriptive statistics were used.

Results: We included data from 13 studies: 4 randomized-controlled trials (RCTs), 4 observational studies, 4 open-label studies, and 1 case series. In these studies, 561 patients were treated with FFA for DS (n = 360), LGS (n = 176), sunflower syndrome (n = 10), CDKL5 deficiency disorder (n = 6), SCN8A-related disorder (n = 3), and other developmental and epileptic encephalopathies (DEEs; n = 6). Of these, 396 (70.6%) patients experienced GTCS or TCS at baseline. FFA was generally initiated at 0.2 mg/kg/day and titrated per protocol or physician discretion; mean/median FFA exposure: 12 weeks to 16 years. In three studies, the reduction in GTCS or TCS was included as part of the overall seizure type evaluated. In 8 studies (including the 4 RCTs), the median percent reduction in GTCS ranged from 45.7 to 90.8%. Among eight studies providing data, seven reported at least half of the patients experienced ≥75% reduction in GTCS or TCS; five studies reported more than half of patients were GTCS-free after FFA treatment.

Conclusion: These results indicate that FFA led to a clinically significant reduction in GTCS or TCS frequency in patients with rare epilepsy syndromes. Further research is needed to determine the impact of FFA on sudden unexpected death in epilepsy (SUDEP) in those patient populations (funded by UCB Pharma).

Publication History

Article published online:
13 November 2023