Fluoxetine as adjunctive therapy in pediatric patients with refractory epilepsy: A retrospective analysis

Approximately 30 % of children with epilepsy develop refractory epilepsy, which has a major impact on neurodevelopmental processes, cognitive functioning, and daily life. Furthermore, children with highly refractory epilepsy are at particular risk of sudden unexpected death. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has shown antiseizure action and was associated with a decreased severity of peri-ictal hypoxemia in adult patients with focal epilepsy. However, therapeutic studies on SSRI use in children are scarce - particularly in epileptic patients. We retrospectively recruited 14 pediatric patients; inclusion criteria were i) refractory epilepsy ii) frequent generalized or focal seizures (more than 1/week) iii) treated with fluoxetine as adjunctive therapy for one month at least. We analyzed their clinical outcome (efficacy and tolerance). The median age at fluoxetine initiation was 9.5 years (2-19), and fluoxetine was combined with a median number of 4 (2-6) anti-seizure medications. The median dose of fluoxetine at the last follow-up was 0.4 mg/kg/day (0.2-0.8). Among the 14 patients, we observed 6 (43 %) good responders. Complete freedom from seizures with cyanosis was reached in 3 (21 %) patients, and only one patient with early-onset epilepsy related to an FHF1 mutation was completely seizure-free. None of the recruited patients experienced seizure worsening, and 8 patients showed no effect on seizure frequency. Fluoxetine as adjunctive therapy in refractory epilepsy could be a beneficial therapeutic option. Future prospective, randomized and controlled studies are needed to study the efficacy of fluoxetine better.