Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 May 10;5(5):CD009887.
doi: 10.1002/14651858.CD009887.pub4.

Stiripentol add-on therapy for focal refractory epilepsy

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

Stiripentol add-on therapy for focal refractory epilepsy

Francesco Brigo et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: This is an updated version of the Cochrane review last published in 2015 (Issue 10). For nearly 30% of people with epilepsy, seizures are not controlled by current treatments. Stiripentol is a new antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 for the treatment of Dravet syndrome as an adjunctive therapy with valproate and clobazam, with promising effects.

Objectives: To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with focal refractory epilepsy who are taking AEDs.

Search methods: For the latest update, we searched the following databases on 21 August 2017: Cochrane Epilepsy Specialized Register, CENTRAL , MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We contacted Biocodex (the manufacturer of stiripentol) and epilepsy experts to identify published, unpublished and ongoing trials.

Selection criteria: Randomised, controlled, add-on trials of stiripentol in people with focal refractory epilepsy.

Data collection and analysis: Review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 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. Only one study was included from the earlier review (32 children with focal epilepsy). This study adopted a 'responder enriched' design and found no clear evidence of a reduction in seizure frequency (≥ 50% seizure reduction) (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82, low-quality evidence) nor evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43, low-quality evidence) when add-on stiripentol was compared 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-quality evidence). When specific adverse events were considered, confidence intervals were very wide and showed the possibility of substantial increases and small reductions in risks of neurological (RR 2.65, 95% CI 0.88 to 8.01, low-quality evidence) or gastrointestinal adverse effects (RR 11.56, 95% CI 0.71 to 189.36, low-quality evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47, low-quality evidence), which was high in both groups (35.0% in add-on placebo and 53.3% in stiripentol group, low-quality evidence). The external validity of this study was limited because only responders to stiripentol (i.e. patients experiencing a ≥ 50% decrease in seizure frequency 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 seemed to occur significantly more often with add-on stiripentol than with add-on placebo.

Authors' conclusions: Since the last version of this review was published, we have found no new studies. Hence, we have made no changes to the conclusions of this update as presented in the initial review. We can draw no conclusions to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Additional large, randomised, well-conducted trials are needed.

PubMed Disclaimer

Conflict of interest statement

Francesco Brigo: none known Nicola L. Bragazzi: none known Stanley C. Igwe: none known

Figures

1
1
Study flow diagram. The results shown in this figure refer both to the searches conducted in the present version of the review and in its previous versions (Brigo 2014; Brigo 2015).
1.1
1.1. Analysis
Comparison 1 Add‐on stiripentol versus placebo, Outcome 1 ≥ 50% seizure reduction.
1.2
1.2. Analysis
Comparison 1 Add‐on stiripentol versus placebo, Outcome 2 Seizure freedom.
1.3
1.3. Analysis
Comparison 1 Add‐on stiripentol versus placebo, Outcome 3 ≥ 1 adverse effect.
1.4
1.4. Analysis
Comparison 1 Add‐on stiripentol versus placebo, Outcome 4 Neurological adverse effects.
1.5
1.5. Analysis
Comparison 1 Add‐on stiripentol versus placebo, Outcome 5 Gastrointestinal adverse effects.
1.6
1.6. Analysis
Comparison 1 Add‐on stiripentol versus placebo, Outcome 6 Dropouts.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Chiron 2006 {published data only}
    1. Chiron C, Tonnelier S, Rey E, Brunet ML, Tran A, d'Athis P, et al. Stiripentol in childhood partial epilepsy: randomized placebo‐controlled trial with enrichment and withdrawal design. Journal of Child Neurology 2006;21(6):496‐502. - PubMed
    1. Chiron C, Tran A, Rey E, d'Athirs P, Vincent J, Tonnelier S, et al. Stiripentol in childhood partial epilepsy: a placebo‐controlled trial. Epilepsia 2000;41:Suppl 7:191. - PubMed

References to studies excluded from this review

Chiron 2000 {published data only}
    1. Chiron C, Tran A, Rey E, d'Athirs P, Vincent J, Tonnelier S, et al. Stiripentol in childhood partial epilepsy: a placebo‐controlled trial. Epilepsia 2000;41(Suppl.7):191. - PubMed
Loiseau 1988 {published data only}
    1. Loiseau P, Strube E, Tor J, Levy RH, Dodrill C. Neurophysiological and therapeutic evaluation of stiripentol in epilepsy. Preliminary results. Revue Neurologique 1988;144(3):165‐72. - PubMed
Loiseau 1990 {published data only}
    1. Loiseau P, Levy RJ, Houin G, Rascol O, Dordain G. Randomized double‐blind, parallel, multicenter trial of stiripentol added to carbamazepine in the treatment of carbamazepine‐resistant epilepsies. An interim analysis. Epilepsia 1990;31(5):618‐9.
Perez 1999 {published data only}
    1. Perez J, Chiron C, Musial C, Rey E, Blehaut H, d'Athis P, et al. Stiripentol: efficacy and tolerability in children with epilepsy. Epilepsia 1999;40(11):1618‐26. - PubMed
Rascol 1989 {published data only}
    1. Rascol O, Squalli A, Montastruc JL, Garat A, Houin G, Lachau S, et al. A pilot study of stiripentol, a new anticonvulsant drug, in complex partial seizures uncontrolled by carbamazepine. Clinical Neuropharmacology 1989;12(2):119‐23. - PubMed

Additional references

Berg 2006
    1. Berg AT, Kelly MM. Defining intractability: comparisons among published definitions. Epilepsia 2006;47(2):431‐6. - PubMed
Berg 2010
    1. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51(4):676‐85. - PubMed
Brigo 2013
    1. Brigo F, Storti M. Antiepileptic drugs for the treatment of severe myoclonic epilepsy in infancy. Cochrane Database of Systematic Reviews 2013, Issue 11. [DOI: 10.1002/14651858.CD010483.pub2] - DOI - PubMed
Chiron 2005
    1. Chiron C. Stiripentol. Expert Opinion on Investigational Drugs 2005;14:905‐11. - PubMed
Chiron 2007
    1. Chiron C. Stiripentol. Neurotherapeutics 2007;4:123. - PMC - PubMed
Cockerell 1995
    1. Cockerell OC, Johnson L, Sander JWAS, Hart YM, Shorvon SD. Remission of epilepsy: results from the National General Practice Study of Epilepsy. Lancet 1995;346:104‐44. - PubMed
Fisher 2009
    1. Fisher JL. The anti‐convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator. Neuropharmacology 2009;56:190‐7. - PMC - PubMed
French 2006
    1. French JA. Refractory epilepsy: one size does not fit all. Epilepsy Currents 2006;6:177‐80. - PMC - PubMed
Giraud 2006
    1. Giraud C, Treluyer JM, Rey E, Chiron C, Vincent J, Pons G, et al. In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism. Drug Metabolism and Disposition 2006;34:608‐11. - PubMed
Granata 2009
    1. Granata T, Marchi N, Carlton E, Ghosh C, Gonzalez‐Martinez J, Alexopoulos AV, et al. Management of the patient with medically refractory epilepsy. Expert Review of Neurotherapeutics 2009;9:1791‐802. - PMC - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐YtterY, Alonso‐Coello P, et al. GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924‐6. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
International League Against Epilepsy 1989
    1. International League Against Epilepsy. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389‐99. - PubMed
Kwan 2010
    1. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51:1069‐77. - PubMed
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org/.
Quilichini 2006
    1. Quilichini PP, Chiron C, Ben‐Ari Y, Gozlan H. Stiripentol, a putative antiepileptic drug, enhances the duration of opening of GABA‐A receptor channels. Epilepsia 2006;47:704‐16. - PubMed
Strauss 2005
    1. Strauss S, Richardson W, Glasziou P, Haynes R. Evidence‐Based Medicine: How to Practice and Teach EBM. 3rd Edition. Edinburgh, United Kingdom: Churchill Livingstone, 2005.

References to other published versions of this review

Brigo 2012
    1. Brigo F, Storti M. Stiripentol for focal refractory epilepsy. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD009887] - DOI - PubMed
Brigo 2014
    1. Brigo F, Storti M. Stiripentol for focal refractory epilepsy. Cochrane Database of Systematic Reviews 2014, Issue 1. [DOI: 10.1002/14651858.CD009887.pub2] - DOI - PubMed
Brigo 2015
    1. Brigo F, Igwe SC, Bragazzi NL. Stiripentol for focal refractory epilepsy. Cochrane Database of Systematic Reviews 2015, Issue 10. [DOI: 10.1002/14651858.CD009887.pub3] - DOI - PubMed

Publication types

LinkOut - more resources