Fenfluramine reduced seizure frequency in three of four girls with MECP2-related Rett syndrome, according to a retrospective multicenter pediatric case series published in Epilepsy & Behavior.

Researchers in Italy reviewed outcomes for four girls aged about 9–14 with drug-resistant epilepsy who received fenfluramine as an add-on therapy. Three patients showed measurable seizure reductions; one did not respond and stopped treatment after a year.

In the first case, tonic-clonic seizures were halved and tonic seizures disappeared within days of starting fenfluramine. Those benefits persisted for at least nine months, and caregivers reported increased engagement and less irritability. No side effects were recorded.

The second girl’s seizures fell from roughly 40 per month to 10–12 (about a 70% drop). Both tonic-clonic and atypical absence seizures decreased, and improvements in participation and communication were reported at 13 months of follow-up with no side effects documented.

The third patient showed only a 10–12% seizure reduction. Clinicians were unable to reach an ideal weight-based dose because the child developed apathy and slowed movements and thinking. Those side effects resolved after pausing treatment, and fenfluramine was restarted, but seizure reduction remained limited.

The fourth patient had no reduction in seizures after one year and discontinued fenfluramine.

All four patients received routine cardiac surveillance, including ECGs and echocardiograms every six to 12 months; results were consistently normal. The authors note that fenfluramine is already approved as add-on therapy for Dravet and Lennox-Gastaut syndromes and that Rett commonly involves seizures, with prior estimates that about 60% or more of people with Rett experience seizures and roughly one-third have drug-resistant epilepsy.

“Fenfluramine shows promise as add-on therapy in severe [Rett] epilepsy and should be assessed in adequately powered controlled trials,” the researchers wrote. They added that future studies should be prospective, larger, and include long-term monitoring of seizure control and cognitive‑behavioral outcomes.

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Tags: Rett syndrome, fenfluramine, drug-resistant epilepsy, MECP2, add-on therapy

Topics: Neuromodulation, Neuroscience & neuroplasticity, Vagus nerve & taVNS