Authors :
Presenting Author: Mutsuki Takeda, MD – Yokohama City University Graduate School of Medicine
Yu Kitazawa, MD, PhD – Yokohama City University Graduate School of Medicine
Masaki Sonoda, MD, PhD – Yokohama City University Graduate School of Medicine
Keisuke Morihara, MD, PhD – Yokohama City University Graduate School of Medicine
Yosuke Miyaji, MD, PhD – Yokohama City University Graduate School of Medicine
Yuichi Higashiyama, MD, PhD – Yokohama City University Graduate School of Medicine
Katsuo Kimura, MD, PhD – Yokohama City University Medical Center
Naohisa Ueda, MD, PhD – Yokohama City University Medical Center
Hiroshi Doi, MD, PhD – Yokohama City University Graduate School of Medicine
Fumiaki Tanaka, MD, PhD – Yokohama City University Graduate School of Medicine
Rationale:
Fenfluramine (FFA), formerly used as an appetite suppressant, has been repurposed and approved by the Food and Drug Administration and other regulatory authorities for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS). Nonetheless, phase III trial mainly focused on pediatric populations, resulting in limited evidence regarding its efficacy and safety in adults. This study aimed to investigate the effectiveness and safety of FFA in adult patients with LGS.
Methods:
Adult patients with LGS who had a history of FFA treatment were included. The diagnostic criteria followed the classic definition [1], characterized by the persistence of multiple seizure types, cognitive impairment, and documented evidence of slow spike-and-wave complexes (SSW) in their medical records. Patient demographics, efficacy outcomes, and adverse events related to FFA were retrospectively collected from March 2024, when it was approved for LGS in Japan, through May 2025.
Results:
Ten adult patients aged 18–49 were identified. All patients experienced at least a 50% reduction in the frequency of at least one seizure type. Complete remission of generalized tonic–clonic seizure or drop attack was observed in some patients. Reductions in seizure frequency of up to 50% for atypical absence and up to 80% for drop attack were noted. No one needed maintenance doses above the recommended starting minimum of 0.2 mg/kg/day, and six patients (60%) achieved seizure reduction with even lower doses. Adverse events were reported in five patients (50%), primarily somnolence, diarrhea, and anorexia. These adverse events appeared to be dose dependent. A dose reduction to half the initial amount alleviated these effects while maintaining efficacy.
Conclusions:
FFA at low doses may effectively manage seizures in adult patients with LGS while minimizing adverse effects. Larger prospective studies are warranted to validate these findings and establish long-term efficacy and safety in adult patients with LGS.
Reference:
- Asadi-Pooya AA. The new International League Against Epilepsy (ILAE) definition of Lennox-Gastaut syndrome: Practical implications and limitations. J Clin Neurosci. 2023, 115:43-46. https://doi.org/10.1016/j.jocn.2023.07.014
Funding:
JSPS JP19K17039 (to Y.K.)