Abstracts

Rationale: Drug-resistant epilepsy affects about 30% of the patients suffering from any type of epilepsy. Combinations of medications, neuromodulation and epilepsy surgery are the primary treatment options for such patients. Pediatric non-surgical patients pose a treatment challenge to the epileptologists given the limited number of approved medications for early onset drug resistant epilepsies. Stiripentol, a medication that most likely works by increasing the GABA-A inhibition is one such medication. Currently, it is FDA approved for Dravet syndrome but it might also be an effective medication for drug resistant epilepsies other than Dravet syndrome. In this study, we analyze the off-label use of stiripentol in non-Dravet epilepsies.

Methods: We retrospectively reviewed the charts of 28 pediatric patients with drug resistant epilepsies other than Dravet syndrome from 2 institutions in Ohio (Rainbow Babies and Children's Hospital, Cleveland; and Nationwide Children's Hospital, Columbus). Patients with drug-resistant epilepsy with convulsive seizures were included in the study. We looked at the diagnoses, seizure types, concomitant medications and response of seizures to the addition of stiripentol to their regimen. Nine patients with a diagnosis of Lennox-Gastaut syndrome, and 20 patients with other drug-resistant generalized epilepsies were analyzed.

Results: The average number of concomitant anti seizures medications (ASM) was 3.1 with a range of 1 to 5 ASMs. Nineteen out of 28 patients were taking concomitant clobazam. All patients presented with multiple seizure types. The most common seizure type was bilateral tonic-clonic seizures seen in 16 patients, followed by tonic seizures in 7 patients. Myoclonic seizures, and atonic seizures were seen in the rest. Duration of therapy with stiripentol ranged from 100 to 917 days. Seizure response and possible side effects were assessed during clinic visits, epilepsy monitoring unit admissions or phone calls to the office. Treatment failure or success was based on the control of convulsive seizures. Eleven patients had a greater than 90% decrease in seizures from baseline with a 75% decrease in 7 patients from baseline, 50% decrease in 5 patients, 25-50% in 3 and < 25% in 2 patients. Six patients had other ASMs started after stiripentol initiation. Therapy with stiripentol was discontinued in 4 patients, 2 due to side effects and 2 due to inefficacy. One of the patients who discontinued the medication due to side effects was given another trial 1 year later with slower titration with good tolerability and seizure control. The most common side effect seen was sedation in 5 patients, followed by weight loss in 3. 2 patients presented with persistent vomiting. Weight loss and vomiting responded well to the addition of cyproheptadine in 2 patients.

Conclusions: Stiripentol, an anti-seizure medication that enhances the inhibitory action of GABA-A receptors is currently approved by the FDA for use in Dravet syndrome. This medication may also be an effective therapeutic option for pediatric patients with drug-resistant epilepsy other than Dravet syndrome.

Funding: None