This article is a summary of the efficacy and safety of stiripentol (Diacomit), a drug indicated for use in patients with Dravet syndrome as an adjunctive therapy in conjunction with clobazam (Onfi) and valproate (Depakote). Stiripentol was first reported to be helpful in Dravet syndrome in 2000, and was approved in the EU in 2007 and in Canada and Japan in 2012, and in the U.S. in 2018.
Stiripentol is an allosteric modulator of the GABAA receptor. However, it is also an inhibitor of the cell’s metabolizing enzymes, and as such can raise the levels of partner drugs such as clobazam – so, its mode of action is complicated.
Approval was based primarily on two short-term randomized, controlled trials performed in France and Italy, in which 70% of patients experienced a significant reduction in seizure frequency, with 39% becoming seizure-free. These results have been supported and extended by findings from prospective and retrospective open-label studies, some of which have occurred under real-world conditions (that is, freedom to change dosage and adjunctive therapies). In one such study, the efficacy of stiripentol (combined with clobazam and valproate) when started at pediatric age was maintained in mid-adulthood – a quarter of patients experienced seizure‐free periods of > 1 year, although only a few patients achieved complete seizure freedom. It has also been noted that stiripentol initiation can cause a marked reduction in status epilepticus, one of the most serious manifestations for Dravet patients.
Stiripentol as an add-on to clobazam and valproate is generally well tolerated, both in the short and longer-term, with the most common adverse events being sleepiness, loss of appetite, ataxia, weight loss, hypotonia, tremor, and nausea.
In Europe, where stiripentol has been available for over a decade, it has become the most common add-on therapy when it is felt that clobazam plus valproate is no longer providing adequate seizure control. Of course, new candidates for adjunct therapy are always appearing; the recently approved cannabidiol, for example.
Since stiripentol positively impacts the late prognosis of epilepsy, especially when initiated before adolescence, the article suggests it may be worth starting it with young patients even though they are satisfactorily controlled, and pursuing treatment into adulthood.