Relieving the Weight: Fenfluramine’s Re-emergence as Antiseizure Medication for Lennox-Gastaut and Dravet Syndrome

Abstract

Objective:

To review the pharmacology, usage, efficacy, and safety of fenfluramine in treating seizures in pediatric patients with Lennox-Gastaut syndrome or Dravet syndrome.

Data sources:

The PubMed database was searched for studies using the search terms “Lennox-Gastaut Syndrome,” “Dravet Syndrome,” “fenfluramine,” and “Fintepla©.”

Study selection and data extraction:

Articles were selected based on the following criteria: published in English, published between January 1950 and September 2025, and included clinical relevancy for pharmacology, efficacy, and adverse events.

Data synthesis:

In a phase 3 trial, patients with Lennox-Gastaut syndrome experienced a median 26.5% decrease in frequency of drop seizures when taking the 0.7 mg/kg/d dose. In a 2-part phase 2 trial, 54% of patients with Dravet syndrome concurrently taking stiripentol experienced a >50% decrease in monthly seizures at a dosage of 0.4 mg/kg/d; 72.9% of patients with Dravet syndrome not concurrently taking stiripentol experienced a >50% decrease in monthly seizures at a dosage of 0.7 mg/kg/d. Most common adverse effects in both trials included lethargy, decreased weight, and decreased appetite.

Relevance to patient care and clinical practice:

Fenfluramine’s dual mechanism of action makes it uniquely suited to reduce seizure activity after previous failures in treatment. Some providers are hesitant to prescribe fenfluramine due to its historical association with severe cardiovascular risks. However, proper dosage and titration, as well as adherence to the Risk Evaluation and Mitigation Strategy program can sufficiently mitigate risk for the outcome of seizure reduction and increased quality of life.

Conclusions:

As seen through the results of multiple clinical trials, fenfluramine can provide significant seizure reduction for Lennox-Gastaut and Dravet patients with treatment-resistant seizures. Risks can be mitigated through adherence to proper programs and schedules, and can provide enough benefits to outweigh risks in patients with particularly resistant epilepsies.