Fenfluramine May Reduce Seizures in Some Severe Epilepsies

What was studied

This paper combined results from 20 studies of fenfluramine in people with developmental and epileptic encephalopathies (DEEs), a group of severe epilepsy conditions. In total, 1,387 patients were included. The studies looked at how well fenfluramine reduced seizures in different syndromes and age groups, and whether benefits seemed to last over time.

The strongest evidence was in Dravet syndrome. The review also included people with Lennox-Gastaut syndrome, some other DEEs, and adults, but there were fewer data in these groups. Four studies were randomized trials and 16 were observational studies.

What they found

Across all included studies, pooled estimates were 64.8% of patients with at least a 50% drop in seizures, 41.6% with at least a 70% drop, and 11.4% who became seizure-free. About 16.7% had minimal or no benefit.

Results differed by syndrome. Fenfluramine showed lower response estimates in Lennox-Gastaut syndrome than in Dravet syndrome, especially at the 50% and 70% seizure-reduction thresholds. Other DEEs had high response point estimates, but those numbers were informed by only a few studies, so they are less certain.

Adults had a higher estimated seizure-free rate than mixed-age or pediatric groups, but the authors caution that this should be interpreted in light of Dravet syndrome predominance and age-related changes in seizure burden in Dravet syndrome. Longer follow-up, mostly in Dravet syndrome, did not suggest a systematic loss of benefit over time.

Limits of the evidence

This study is a systematic review and meta-analysis, so it combines earlier studies rather than testing the drug directly in one new trial. Most of the evidence came from observational studies rather than randomized trials, which can make results more vulnerable to differences in who was treated and how outcomes were measured.

The evidence was much stronger for Dravet syndrome than for Lennox-Gastaut syndrome, other DEEs, or adults. Some subgroup findings, especially for "other DEEs," were based on very few studies. Follow-up length also varied between studies, so long-term durability is still less certain outside Dravet syndrome.

Because the included conditions are heterogeneous, pooled averages may not apply equally to every syndrome or every patient.

For families and caregivers

For families, this review suggests that fenfluramine may provide clinically meaningful seizure reduction across DEEs, with the strongest evidence in Dravet syndrome. It also suggests that benefit may persist over time, although the best long-term evidence is mainly in Dravet syndrome.

At the same time, results were not the same across all syndromes. Families of children or adults with Lennox-Gastaut syndrome or rarer DEEs should know that the evidence is thinner and average benefit appears less certain than in Dravet syndrome.

What to watch next

More data, especially randomized studies and longer follow-up in adults, Lennox-Gastaut syndrome, and rarer DEEs, would help clarify how consistent and durable the benefits are across groups.

Terms in this summary

developmental and epileptic encephalopathies

A group of severe epilepsy conditions in which ongoing epileptic activity can contribute to worsening problems with development, behavior, movement, or thinking.

Dravet syndrome

A rare epilepsy syndrome that usually begins in infancy and often causes hard-to-control seizures and developmental problems.

Lennox-Gastaut syndrome

A severe epilepsy syndrome, often beginning in childhood, with multiple seizure types and developmental or behavioral difficulties.

systematic review

A study that carefully collects and summarizes all relevant research on a question.

meta-analysis

A method that combines results from multiple studies to estimate overall results.

observational study

A study where researchers observe what happens without randomly assigning treatment.

randomized trial

A study where participants are assigned by chance to different treatments, which usually gives stronger evidence.

seizure freedom

Having no seizures during the study period being measured.