Stiripentol for the treatment of seizures associated with Dravet syndrome in patients 6 months and older and taking clobazam

ABSTRACT

Introduction

Stiripentol (STP) is a structurally unique molecule with anticonvulsant and neuroprotective properties in animal and human studies. STP enhances gamma-aminobutyric acid (GABA)ergic neurotransmission and inhibits multiple hepatic isoenzymes (i.e. cytochrome P450 system) involved in the metabolism of other antiseizure medications (ASMs) potentiating their anticonvulsant effects and has proven to be a promising therapy in Dravet Syndrome (DS).

Areas covered

The authors review randomized clinical trials and observational studies showing STP efficacy, safety, and tolerability when used as adjunctive therapy with VPA and clobazam in patients with DS. Moreover, they include recent evidence of its use in patients<2 years of age.

Expert opinion

Evidence on STP demonstrates clinically meaningful efficacy in both short and long term in patients with DS. In addition to reducing convulsive seizure frequency, STP also markedly reduces the number of status epilepticus episodes and associated medical complications which are more common in younger children. STP adverse effects are generally not severe and often resolve following STP dose reduction or adjustments of concomitant ASMs. STP is approved by the FDA for children aged 6 months and older with DS who are also taking clobazam, making it the only DS-specific ASM for children under age 1 year.

KEYWORDS:

• Developmental and epileptic encephalopathy
• Dravet syndrome
• Refractory epilepsy
• Seizure
• Stiripentol

Article highlights

• STP is a chiral molecule that belongs to the group of aromatic allylic alcohols and exhibits anticonvulsant properties through the enhancement of gamma-aminobutyric acid (GABA)ergic neurotransmission.

• Administration of STP as adjunctive therapy to clobazam and/or VPA in patients with Dravet Syndrome results in significant reduction in convulsive seizure frequency, prolonged seizures, and hospital and emergency department admissions.

• STP has pharmacokinetic interactions with multiple antiseizure medication (e.g. clobazam).

• As a result of these interactions, dose adjustments of concomitant therapies are needed to optimize efficacy and tolerability.

• STP is FDA approved and should be considered as second-line therapy for patients with DS aged 6months and older with inadequately controlled seizures on clobazam and/or valproate.

Declaration of interest

EC Wirrell has received research funding from Biocodex, Zogenix (now UCB), GW Pharma (now Jazz Pharma) and Stoke Therapeutics with monies directed to the Mayo Clinic. Additionally, she has received funding from Encoded Therapeutics for study consultation. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.