• Francesco Brigo and Monica Storti.
• Cochrane Db Syst Rev. 2014 Jan 1;1:CD009887.

BackgroundNearly 30%of people with epilepsy do not have their seizures controlled with current treatments. Stiripentol is a new antiepileptic drug(AED) developed in France and recently approved by the European Medicines Agency (EMA) for the treatment of Dravet syndrome as an adjunctive therapy with valproate and clobazam, with a promising effect.ObjectivesTo evaluate the efficacy and tolerability of stiripentol as add-on treatment for patients with focal refractory epilepsy taking any AEDs.Search MethodsWe searched the Cochrane Epilepsy Group Specialized Register (19 August 2013), Cochrane Central Register of Controlled Trials(CENTRAL Issue 7, The Cochrane Library July 2013), MEDLINE (Ovid) (1946 to 19 August 2013) and EMBASE (31 May 2012).(The last search in EMBASE was made on 31th May 2012. Since then we no longer have access to that database.) We also contacted Biocodex (the manufacturer of stiripentol) and epilepsy experts to identify published, unpublished and ongoing trials.Selection CriteriaRandomised controlled add-on trials of stiripentol in patients with focal refractory epilepsy.Data Collection And AnalysisReview authors independently selected trials for inclusion and extracted data. The outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life.Main ResultsUsing our selection criteria, one study was included (32 children with focal epilepsy). This study adopted a 'responder enriched' design.There was no clear evidence of a reduction in seizure reduction 50% seizure reduction) (RR 1.51, 95% CI 0.81 to 2.82) or in seizure freedom (RR 1.18, 95% CI 0.31 to 4.43) with add on stiripentol compared with placebo. Add-on stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47) compared with placebo. When considered as specific adverse events, the confidence intervals are very wide and include the possibility of substantial increases and small reductions in the risk of neurological (RR 2.65, 95% CI 0.88 to 8.01) or gastrointestinal adverse effects (RR 11.56, 95% CI 0.71 to 189.36). There was no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47), which was high in both groups (35.0% in add-on placebo and 53.3% in stiripentol group). The external validity of the study was limited because only responders to stiripentol (that is patients experiencing at least a 50% decrease in seizure frequency compared with baseline) were included in the randomised add on placebo-controlled double-blind phase. Furthermore, a carry-over and a withdrawal effect probably affected the outcome related to seizure frequency. Although restricted by the very limited information derived by the only one included study, adverse effects considered as a whole seemed to occur significantly more often with add-on stiripentol compared with add-on placebo.Authors' ConclusionsNo conclusions can be drawn to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Further large, randomised,well-conducted trials are needed.

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