Effectiveness and safety of stiripentol in epilepsy: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to evaluate the safety and efficacy of stiripentol (STP) in patients with epilepsy, including those with Dravet syndrome (DS) and status epilepticus (SE). A comprehensive search of PubMed, Scopus, and Web of Science was conducted for articles published up to February 20, 2025. Eligible studies included clinical trials, cohort studies, case series, and cross-sectional analyses assessing STP in epilepsy. Two independent reviewers screened the studies and extracted data. Outcomes included ≥50 ​% seizure reduction, seizure freedom, and adverse events (AEs). Risk of bias was assessed using the Newcastle–Ottawa Scale and Joanna Briggs Institute tools. Meta-analyses were performed using a random-effects model to account for study heterogeneity. Twenty-nine studies ( n ​= ​1445) were included. Overall, 52.2 ​% (95 ​% confidence interval [CI]: 43.1–61.1 ​%) of patients achieved ≥50 ​% seizure reduction, and 12.0 ​% (95 ​% CI: 7.7–18.1 ​%) achieved seizure freedom. Subgroup analyses showed ≥50 ​% seizure reduction in SE (73.9 ​%, 95 ​% CI: 28.6–95.2 ​%), generalized myoclonic seizures and/or generalized atypical absence seizures (65.0 ​%, 95 ​% CI: 50.7–77.0 ​%), focal epilepsy (56.5 ​%, 95 ​% CI: 48.3–64.3 ​%), DS (47.8 ​%, 95 ​% CI: 39.8–56.0 ​%), and generalized tonic–clonic seizures (46.2 ​%, 95 ​% CI: 35.9–56.8 ​%). Seizure freedom was highest in the SE group (31.3 ​%, 95 ​% CI: 16.2–51.6 ​%) and lowest in the DS group (7.9 ​%, 95 ​% CI: 4.6–13.1 ​%). The most common AEs were drowsiness (28.2 ​%, 95 ​% CI: 18.6–37.7 ​%), behavioral changes (24.5 ​%, 95 ​% CI: 9.2–39.7 ​%), weight loss (22.6 ​%, 95 ​% CI: 14.2–31.1 ​%), and decreased appetite (22.0 ​%, 95 ​% CI: 14.7–29.3 ​%). Treatment discontinuation due to AEs occurred in 7.2 ​% (95 ​% CI: 3.6–10.8 ​%) of patients. STP is a well-tolerated and effective adjunctive treatment for refractory epilepsy, particularly in SE and DS. It significantly reduces seizure frequency, with a meaningful rate of seizure freedom in SE. Most AEs were mild, supporting the clinical value of STP in patients with difficult-to-treat epilepsy.