(Nickels KC, Wirrell EC 2017). This article reviews the current knowledge on stiripentol (Diacomit), as related to its mechanism of action (including its effects on the GABA-A receptor and inhibition of lactate dehydrogenase, a key enzyme in the brain used in the conversion of lactate to pyruvate); inhibition of several cytochrome P450 enzymes; safety and tolerability; and efficacy.
Enzyme inhibition results in increased plasma concentration (measured blood levels) of many AEDs when stiripentol is added to treatment. Affected AEDs include clobazam, phenobarbital, phenytoin, carbamazepine, valproate, diazepam, ethosuximide, and tiagabine, and doses must be adjusted accordingly. There is some evidence that stiripentol has a neuroprotective effect, decreasing cell injury after status epilepticus; oxygen or glucose deprivation; or high levels of glutamate.
There are several studies on efficacy in Dravet syndrome and it is currently approved in Europe, Canada, and Japan for the treatment of Dravet syndrome. It is not US FDA-approved and requires an Investigational New Drug (IND) application for each prescription. Traditionally, stiripentol is prescribed in conjunction with clobazam and valproic acid. A recent US-based retrospective study of 82 patients showed a roughly 80% responder rate for stiripentol with clobazam but without valproic acid, 57% for stiripentol with valproic acid but without clobazam, and 63% for stiripentol with clobazam and valproic acid.