ObjectiveTo investigate the effectiveness and safety of Perampanel (PER) add-on treatment in the pediatric patients with uncontrolled epilepsy. MethodsPatients aged 0 ~ 18 years who visited the Xi'an Children's Hospital between June 2021 and December 2024 were recruited. They had uncontrolled seizures and were treated with PER as add-on therapy. The outcomes included response rate, seizure-free rate, and retention rate at 3, 6, and 12 months, and at the last visit. Tolerability was also assessed throughout follow-up. ResultsA total of 105 pediatric patients with epilepsy were followed up for at least 6 months. Eighty-three cases were aged ≥4 years while 22 cases were aged <4 years. Focal seizures occurred in 76 (72.4%) cases and 29 (27.6%) cases suffered other seizure types. The cause of epilepsy was clarified in 46 (43.8%) cases. The diagnosis of epileptic syndrome could be established in 34 (32.4%) cases at the time of PER add-on. The median seizure frequency per 28 days was 8 at baseline. The median number of prior antiseizure therapy before PER add-on was 3. The overall response rates at 3, 6 and 12 months were 61.9%, 63.8%, and 64.7%, respectively. The seizure-free rates were 39.0%, 42.9%, and 52.9%, respectively. There was no significant difference in the response rate between focal seizures and other seizure types at the last visit (69.7% vs. 51.7%, P=0.084). No significant difference was perceived in the response rate between patients aged ≥4 years and those aged <4 years as well (68.7% vs. 50%, P=0.103). Multivariate Logistic regression analysis showed that the effectiveness of PER was probably related to the maintenance dose and numbers of pervious treatments. At the last visit, the retention rate of PER was 80.0% and the adverse events (AEs) occurred in 30.0% patients. The most common AEs include somnolence/sleepy in 12 (11.4%) cases and dizziness in 8 (7.6%) cases. ConclusionPER add-on treatment has a good effectiveness, safety and tolerability in the pediatric patients with epilepsy. It is probably that the effectiveness is related to the maintenance dose and previous treatment numbers.