What is drug-resistant epilepsy?
Epilepsy is one of the more common long-lasting neurological disorders; it affects 1% of the population worldwide. Up to 30% of people with epilepsy continue to have seizures (sudden bursts of electrical activity in the brain that change how it works for a short time) despite adequate therapy with antiepileptic medicines. These people are regarded as having drug-resistant epilepsy.
What did we want to find out?
Antiepileptic medicines can be used singularly (as monotherapy) or in combination (polytherapy). Stiripentol is an antiepileptic medicine that was developed in France and was approved in 2007 by the European Medicines Agency as add-on therapy with valproate and clobazam for the treatment of Dravet syndrome (a rare, drug-resistant epilepsy that begins in the first year of life in an otherwise healthy infant). This review assesses the evidence for the use of stiripentol as add-on treatment for drug-resistant focal epilepsy in people taking antiepileptic medicines.
What did we find?
On the basis of our review criteria, we included only one study in the review. In the included study, 67 children were given a dummy medicine (placebo) in addition to their usual treatment for one month, and were then given add-on stiripentol (without the placebo) for four months. The 32 children who responded to stiripentol (who had half the number of seizures or fewer when taking stiripentol compared with during the first month) were included in the next part of the study. Seventeen of these children continued add-on stiripentol, while the other 15 received add-on placebo. This stage of the study was randomised and double-blind (the treatment was allocated at random, and neither the children nor the doctors knew who was receiving what treatment).
After two months, the study authors found no clear differences between the two treatment groups in terms of seizure reduction (the number of children with half the number of seizures or fewer) or seizure freedom (the number of children who had no seizures). However, the children taking stiripentol were more likely to have harmful side effects than those taking the placebo. The results of the study may not apply to a more general population because it only included children who responded to stiripentol.
What are the limitations of the evidence?
We have little confidence in the evidence because the study included a small number of children, several children left the study before the end, and the treatment given to all children in the first part of the study might have affected the number of seizures in the randomised, double-blind part of the study.
Currently, no available evidence supports the use of stiripentol as add-on treatment for drug-resistant focal epilepsy. Large, randomised, well-conducted trials on this topic are needed.
The evidence is current to March 2022.
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.
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.
To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with drug-resistant focal epilepsy who are taking AEDs.
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.
Randomised controlled trials of add-on stiripentol in people with drug-resistant focal epilepsy.
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.
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.