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Stiripentol: A Review in Dravet Syndrome

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Abstract

Stiripentol (Diacomit®) is an orally-active, structurally unique anti-epileptic drug (AED) with multiple potential mechanisms of action, including enhancement of central γ-aminobutyric acid transmission. In the EU, stiripentol is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with Dravet syndrome (DS; previously known as severe myoclonic epilepsy of infancy), whose seizures are not adequately controlled with clobazam and valproate. This approval (and similar DS indications in the USA, Canada and Japan), reflect the results of the STICLO studies, two small, randomized controlled trials in which stiripentol as adjunctive therapy was associated with a markedly superior response rate after 2 months compared with placebo in patients aged between 3 and ≈ 21 years with DS that was inadequately controlled with clobazam and valproate. These short-term results have subsequently been supported and extended by findings from longer-term, open-label, observational studies, including a retrospective longitudinal cohort study, which showed that the efficacy of combining stiripentol with clobazam and valproate when started at paediatric age was maintained in mid-adulthood with up to 24 years of exposure, and up to 40 years of age. Drowsiness, appetite loss, weight loss, ataxia and tremor are the most common adverse events associated with the addition of stiripentol to clobazam and valproate. Based on the available evidence, stiripentol, as an adjunct to clobazam and valproate, is a demonstrably beneficial and generally well-tolerated second-line treatment for patients with DS.

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Acknowledgements

During the peer review process, the manufacturer of stiripentol was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    James E. Frampton

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The preparation of this review was not supported by any external funding.

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James Frampton is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.

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Enhanced material for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.9876596.

The manuscript was reviewed by:S. Balestrini, Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; C. Chiron, INSERM U1141, Neurospin (CEA) and Neuropediatric Department, Necker Enfants-Malades Hospital, Paris, France; C. Dravet, Childhood Neuropsychiatry, Catholic University, Rome, Italy; A. Strzelczyk, Department of Neurology, Epilepsy Center Frankfurt Rhine‐Main, Goethe University, Frankfurt am Main, Germany; A. Verrotti, Department of Pediatrics, University of L’Aquila, L’Aquila, Italy.

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Frampton, J.E. Stiripentol: A Review in Dravet Syndrome. Drugs 79, 1785–1796 (2019). https://doi.org/10.1007/s40265-019-01204-y

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