Fenfluramine Cut Seizures In Children And Adults

What was studied

This study looked at fenfluramine, a seizure medicine, in children and adults with developmental and epileptic encephalopathies (DEEs). DEEs are severe epilepsy conditions characterized by drug-resistant seizures and developmental slowing or regression. The study included 166 patients from multiple centers in Spain: 84 with Lennox-Gastaut syndrome, 42 with Dravet syndrome, and 40 with other DEEs.

It was a retrospective real-world study, which means researchers reviewed information already recorded in medical charts rather than assigning treatment in a trial. Patients had started fenfluramine at least 12 months before the database closed. The mean age was 16.6 years; 111 were pediatric patients and 55 were adults. Before fenfluramine, patients had already tried a median of 3 anti-seizure medicines that had failed.

What they found

After 12 months, seizure frequency was reduced by a median of 68.8% compared with baseline. About 61% of patients had at least a 50% drop in seizures at 12 months. Seizure reductions were statistically significant in the Lennox-Gastaut, Dravet, and other DEE groups, and the abstract reports no statistically significant differences in the ≥50% responder rate according to age.

The study also found that, by 12 months, the mean number of other anti-seizure medicines was lower, and a smaller proportion of patients required rescue medicine. Doctors also recorded meaningful improvement in Clinical Global Impression scores in some non-seizure areas: cognition in 59.3% of patients, behavior in 40.9%, sleep in 24.3%, and caregiver domain in 44.8%.

Adverse events were reported in 68.1% of patients and were mostly mild to moderate. Adverse events led 12% of patients to stop fenfluramine. About 77.1% of patients were still taking fenfluramine at 12 months.

Limits of the evidence

This study cannot show from the abstract alone that fenfluramine by itself caused the improvements, because it was not a randomized controlled trial and there was no comparison group. It used chart review, so results depend on what was recorded in routine care.

The study combined several different DEE diagnoses, which may not all respond the same way. Some outcomes, such as cognition, behavior, sleep, and caregiver domain, were based on Clinical Global Impression ratings, which are useful but somewhat subjective. The abstract does not give details about which adverse events were most common, and it does not provide results beyond 12 months.

For families and caregivers

For families, this study suggests that fenfluramine may help reduce seizures in some children and adults with severe, hard-to-treat epilepsies, including Lennox-Gastaut syndrome, Dravet syndrome, and some other DEEs. It also suggests that some patients were taking fewer other seizure medicines or were less likely to need rescue medicines by 12 months.

At the same time, adverse events were common, even if usually mild to moderate, and some patients stopped treatment because of them. This means the medicine may be a helpful option for some people, but careful follow-up is still important.

What to watch next

Stronger evidence would come from longer-term studies and controlled trials that compare fenfluramine with other treatment options in different DEE groups.

Terms in this summary

developmental and epileptic encephalopathies (DEEs)

A group of severe epilepsy disorders characterized by drug-resistant seizures and developmental slowing or regression.

Lennox-Gastaut syndrome (LGS)

A severe epilepsy syndrome with multiple seizure types and developmental problems.

Dravet syndrome (DS)

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

retrospective study

A study that looks back at existing medical records instead of following people forward in a planned trial.

median

The middle value in a group of numbers, so half are higher and half are lower.

responder rate

The percentage of patients who reached a set level of improvement, such as at least a 50% drop in seizures.

adverse event (AE)

A side effect or unwanted medical problem that happens during treatment.

rescue medication

Medicine used quickly to stop or reduce a seizure emergency or seizure cluster.