Stiripentol As An Adjuvant Therapy For Dravet Syndrome:A Meta-analysis Of Effectiveness And Safety

Background: Dravet syndrome(DS) was put forward by the French physician Dravet first time in 1978, formerly known as infant severe myoclonic epilepsy(Severe Myoclonic Epilepsy Of Infancy, SMEI) [1]. DS often occurs in the first year of life, with or without febrile seizures.The most common onset form of seizure is myoclonic seizures, atypical absence seizures and focal seizures.With the development of the course,regress of cognitive function and behavioral disorders will happen to the patient, the quality of the patients' life could be seriously impacted on. With the gradual deepening of DS research and diagnosis of the disease gradually increased, more and more patients are diagnosed DS earlier. DS is a severe epileptic encephalopathy, the main traditional antiepileptic drugs treatment is valproate joint clobazam, but the treatment is not good enough to have a control of the seizures and there is resistance. Therefore, the search for new treatment of epilepsy in children is a hot spot. Stiripentol: also known as benzene dioxide heptanol(stiripentol, STP),is a new anti-epileptic drugs, often used as adjuvant therapy for a variety of refractory epilepsy, in recent years, many scholars as an auxiliary STP Drug used in the treatment of DS.Objective: To evaluate the efficacy and safety of stiripentol as an add-on therapy to Dravet syndrome compared with placebo.Search strategy: Chinese database includes Chinese Biomedical Literature Database(CBM), China Journal Full-text Database(CNKI), VIP database(VIP)and Wanfang database; Keyword use stiripentol, STP, Dravet syndrome, severe muscle baby clonic seizures, SMEI. Searchable database including Embase1974 to 2016 March 18, Medline 1946 to 2016 March 18, Cochrane Epilepsy Group's Specialized Register(18 March 2016) and the Cochrane Central Register of Controlled Trials(CENTRAL, The Cochrane Library Issue 18 of3,2012).Inclusion criteria: randomized controlled trials or quasi-randomized controlled trials.Collection and analysis of data:Two authors independently process the data, including screening literature,literature quality assessment, data extraction and analysis, summary and concluding observations together again reviewed in order to reduce the risk of subjective offset.Results: There are totally included two randomized controlled trials of stiripentol as an add-on therapy to Dravet syndrome,combined with valproate and clobazam for Dravet syndrome seizure frequency control action analysis(stiripentol use a dose of 50 mg / kg / 24h). Meta analysis: stiripentol as add-on therapy to reduce the effectiveness of Dravet seizure of more than 50% and50% was significantly higher than the placebo group, the difference was statistically significant(22/33 vs 2/31; RR 10.40, 95 % CI 2.64 to 40.87), the effectiveness of stiripentol as add-on therapy for Dravet complete control of seizures was significantly higher than the placebo group, the difference was statistically significant(12/33 vs 1/31; RR 7.93, 95% CI 1.52 to 41.21). Of which only one reported stiripentol reported the side effects,include: lethargy,loss of appetite, weight loss or gain, stiripentol related side effects as compared to placebo added to treatment, the difference was statistically significant(95%vs 25%; RR 3.82, 95% CI 1.78 to 8.20).Conclusion: There is limited based on the best evidence which we can find shows that stiripentol as an add-on therapy programs, joint valproate and clobazam for Dravet syndrome seizure control has a good effect, but stiripentol as adjuvant therapy for drug-related side effects also increased significantly,simply can not be determined from the two papers included in the side effects of stiripentol generating mechanism has a direct relationship, or because the use of the stiripentol which can increases the drug concentration in the blood of clobazam and valproate caused side effects,so whether it should be appropriate to reduce the amount of drug clobazam need further proof. The current need for more high-quality and large sample randomized, double-blind controlled clinical monotherapy trials, efforts to strengthen the evidence that stiripentol adjuvant treatment of Dravet syndrome results demonstrate the effectiveness and safety of a more comprehensive and objective.