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. 2022 Sep 6;9(9):CD009887.
doi: 10.1002/14651858.CD009887.pub6.

Stiripentol add-on therapy for drug-resistant focal epilepsy

Francesco Brigo  1 , Stanley C Igwe  2 , Nicola Luigi Bragazzi  3
Affiliations

Stiripentol add-on therapy for drug-resistant focal epilepsy

Francesco Brigo et al. Cochrane Database Syst Rev. .

Abstract

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 We contacted the manufacturer of stiripentol and epilepsy experts to identify published, unpublished and ongoing trials.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.

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Conflict of interest statement

FB: none SI: none NB: none

Figures

1
1
Study flow diagram. The results shown in this figure include the original searches conducted for the review and all subsequent updates.
1.1
1.1. Analysis
Comparison 1: Add‐on stiripentol versus add‐on placebo, Outcome 1: ≥ 50% seizure reduction
1.2
1.2. Analysis
Comparison 1: Add‐on stiripentol versus add‐on placebo, Outcome 2: Seizure freedom
1.3
1.3. Analysis
Comparison 1: Add‐on stiripentol versus add‐on placebo, Outcome 3: ≥ 1 adverse effects
1.4
1.4. Analysis
Comparison 1: Add‐on stiripentol versus add‐on placebo, Outcome 4: Neurological adverse effects
1.5
1.5. Analysis
Comparison 1: Add‐on stiripentol versus add‐on placebo, Outcome 5: Dropouts
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to other published versions of this review

Brigo 2012
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Brigo 2014
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Brigo 2015
    1. Brigo F, Igwe SC, Bragazzi NL. Stiripentol for focal refractory epilepsy. Cochrane Database of Systematic Reviews 2015, Issue 10. Art. No: CD009887. [DOI: 10.1002/14651858.CD009887.pub3] - DOI - PubMed
Brigo 2018
    1. Brigo F, Igwe SC, Bragazzi NL. Stiripentol add-on therapy for focal refractory epilepsy. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No: CD009887. [DOI: 10.1002/14651858.CD009887.pub4] - DOI - PMC - PubMed
Brigo 2020
    1. Brigo F, Igwe SC, Bragazzi NL. Stiripentol add-on therapy for drug-resistant focal epilepsy. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No: CD009887. [DOI: 10.1002/14651858.CD009887.pub5] - DOI - PMC - PubMed

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