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Objective: To analyze the occurrence of adverse drug events (ADEs) associated with Stiripentol (STP) use in children aged 0-17 years in real-world clinical settings., Methods: ADE reports on STP in children aged 0-17 years were collected from the WHO Global Case Safety Pathology Reporting Database (VigiBase), the U.S. Food and Drug Administration's Spontaneous Adverse Event Reporting System database (FAERS), and the European Medicines Agency's Pharmacovigilance database (Eudra Vigilance). Pharmacovigilance signals were identified through Reporting Odds Ratio (ROR), and Proportional Reporting Ratio (PRR)., Results: In total, 31,990 ADEs were reported with "Stiripentol" as the primary suspect drug. This includes 595 ADEs from the Eudra Vigilance, 1,353 ADEs from the FAERS, and 998 ADEs from the VigiBase. All three databases indicate a higher incidence of ADEs related to STP in the categories of nervous system disorders, general disorders and administration site conditions, injury, poisoning and procedural complications, and metabolism and nutrition disorders. A higher proportion of children aged 3-11 years reported (16.48 %-32.44 %). The FAERS data shows that cerebellar atrophy (PRR of 332.94, ROR of 532.10) is the strongest signal for children aged 0-2 years, while changes in seizure presentation (PRR of 110.76, ROR of 121.06) is the strongest signal for children aged 3-11 years. For children aged 12-17 years, seizures (PRR of 46.99, ROR of 47.40) and decreased appetite(PRR of 45.51, ROR of 45.96) are the strongest signals. The Eudra Vigilance results show that boys have higher ADEs than girls for investigations, blood and lymphatic system disorders, hepatobiliary disorders, infections and infestations in children aged 0-17 years. On the other hand, girls have higher ADEs than boys for skin and subcutaneous tissue disorders, injury, poisoning and procedural complications, general disorders and administration site conditions, and gastrointestinal disorders., Conclusion: In the clinical application of STP in pediatrics, it is important to examine ADEs in Nervous system disorders, Injury, poisoning and procedural complications, General disorders and administration site conditions, and Metabolism and nutrition disorders. Further studies should confirm whether there are age and gender differences in different ADEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first-line add-on therapies in DS., Methods: We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trial (RCT) data for licensed add-on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% (clinically meaningful), ≥75% (profound), and 100% (seizure-free); serious adverse events (SAEs); discontinuations due to AEs., Results: We identified relevant data from two placebo-controlled RCTs for each drug. Stiripentol 50 mg/kg/day and fenfluramine 0.7 mg/kg/day had similar efficacy in achieving ≥50% (clinically meaningful) and ≥75% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: -20% to 22%; p = 0.93] and 6% [-15% to 27%; p = 0.59], respectively), and both were statistically superior (p < 0.05) to licensed dose regimens of cannabidiol (10 or 20 mg/kg/day, with/irrespective of clobazam) for these outcomes. Stiripentol was statistically superior in achieving seizure-free intervals compared to fenfluramine (RD = 26% [CI: 8% to 44%; p < 0.01]) and licensed dose regimens of cannabidiol. There were no significant differences in the proportions of patients experiencing SAEs. The risk of discontinuations due to AEs was lower for stiripentol, although the stiripentol trials were shorter., Significance: This NMA of RCT data indicates stiripentol, as a first-line add-on therapy in DS, is at least as effective as fenfluramine and both are more effective than cannabidiol in reducing convulsive seizures. No significant difference in the incidence of SAEs between the three add-on agents was observed, but stiripentol may have a lower risk of discontinuations due to AEs. These results may inform clinical decision-making and the continued development of guidelines for the treatment of people with DS., Plain Language Summary: This study compared three drugs (stiripentol, fenfluramine, and cannabidiol) used alongside other medications for managing seizures in a severe type of epilepsy called DS. The study found that stiripentol and fenfluramine were similarly effective in reducing seizures and both were more effective than cannabidiol. Stiripentol was the best drug for stopping seizures completely based on the available clinical trial data. All three drugs had similar rates of serious side effects, but stiripentol had a lower chance of being stopped due to side effects. This information can help guide treatment choices for people with DS., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: This is an updated version of the Cochrane Review first published in 2014 and last updated in 2020. For nearly 30% of people with epilepsy, current treatments do not control seizures. Stiripentol is an antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 as an adjunctive therapy with valproate and clobazam for the treatment of Dravet syndrome., Objectives: To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with drug-resistant focal epilepsy who are taking AEDs., Search Methods: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE on 28 March 2022. We contacted the manufacturer of stiripentol and epilepsy experts to identify published, unpublished and ongoing trials., Selection Criteria: Randomised controlled trials of add-on stiripentol in people with drug-resistant focal epilepsy., Data Collection and Analysis: Review authors independently selected trials for inclusion and extracted data. We investigated outcomes including 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life., Main Results: On the basis of our selection criteria, we included no new studies in the present review update. We included only one study from the original review (32 children with focal epilepsy). This study adopted a responder-enriched design and found no clear evidence of a reduction of 50% or more in seizure frequency (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82; low-certainty evidence) and no clear evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43; low-certainty evidence) when comparing add-on stiripentol with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47; low-certainty evidence). When we considered specific adverse effects, CIs were very wide and showed the possibility of substantial increases and small reductions in risks of neurological adverse effects (RR 2.65, 95% CI 0.88 to 8.01; low-certainty evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47; low-certainty evidence), which was high in both groups (53.3% in placebo group and 35.3% in stiripentol group; low-certainty evidence). The external validity of this study was limited because only responders to stiripentol (i.e. participants experiencing a decrease in seizure frequency of 50% or greater during an open prerandomisation phase compared with baseline) were included in the randomised, add-on, placebo-controlled, double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole may occur more often with add-on stiripentol than with add-on placebo., Authors' Conclusions: We have found no new studies since the last version of this review was published. Hence, we have made no changes to the conclusions as presented in previous versions. We can draw no conclusions to support the use of stiripentol as add-on treatment for drug-resistant focal epilepsy. Additional large, randomised, well-conducted trials are needed., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)