Stiripentol and vigabatrin current roles in the treatment of epilepsy

ABSTRACT

Introduction: Stiripentol and vigabatrin are the two anticonvulsant drugs currently approved in severe infantile-onset epilepsies, respectively Dravet syndrome and infantile spasms.

Areas covered: For both, the indication was discovered by chance thanks to an exploratory study. Both demonstrated indisputable efficacy through randomized-controlled trials. Stiripentol as adjunctive therapy to clobazam and valproate performed better than placebo, and vigabatrin as first-line monotherapy better than the reference steroid therapy in spasms due to tuberous sclerosis. At one-year treatment vigabatrin and steroids were equally efficient in the other etiologies of spasms. However, it took more than 20 years for both drugs to be approved world-wide.

Expert opinion: Stiripentol suffered from pharmacokinetic potentiation of clobazam, thus raising the question whether it was efficient per se. Finally, animal models and pharmacogenetic data on CYP2C19 confirmed its specific anticonvulsant effect. Stiripentol (in comedication with clobazam and valproate) is therefore to be recommended for Dravet patients. Vigabatrin was found to have a frequent and irreversible retinal toxicity, which required an alternative visual testing to be detected in young children. Today the benefit/risk ratio of vigabatrin as first-line is considered to be positive in infantile spasms, given the severity of this epilepsy and the lack of a safer alternative therapy.

KEYWORDS:

• Antiepileptic drug trials
• clobazam
• CYP2C19
• drug-drug interactions
• dravet syndrome
• Electroretinogram
• infantile spasms
• stiripentol
• vigabatrin
• visual field loss

Article highlights

• STP and VGB are the only ‘new’ AEDs currently approved for infantile-onset epileptic encephalopathies, respectively, for DS and West syndrome (IS).

• STP and VGB both benefited from a clinical strategy based on an exploratory/confirmatory sequence in order to minimize the risk missing new therapeutic possibilities and to maximize the power of controlled trials.

• STP (in comedication with CLB and VPA) is to be recommended for Dravet patients with refractory seizures as soon as the first year of life.

• A dose adjustment of CLB is required when it is used as comedication with STP.

• VGB is to be recommended as first-line drug in IS due to TS. In the other etiologies of IS, the benefit/risk ratio of VGB as first-line drug remains positive.

• ERG is to be recommended to control the retinal toxicity of VGB in the young patients unable to perform visual-field testing.

This box summarizes key points contained in the article.

Declaration of interest

C Chiron has held scientific advisory roles for BIOCODEX (2013–2015), Brabant Pharma (2014 & 2015), Zogenix (2015), UCB Pharma (2015), and Bial (2015). She has received conference fees from BIOCODEX (2012–2014), Novartis (2012), Desitin Pharma (2014) and has received reimbursement for seminar attendance from BIOCEDEX (2012–2014), Novartiz (2012), ViroPharma (2013), Desitin Pharma (2014) and Advicenne Pharma (2015). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.