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Successful treatment of adult Dravet syndrome patients with cenobamate

Dravet syndrome (DS) is a rare, drug‐resistant, severe developmental and epileptic encephalopathy caused by pathogenic variants in the α subunit of the voltage‐gated sodium channel gene SCN1A. Hyperexcitability in DS results from loss of function in inhibitory interneurons. Thus sodium channel blockers are usually contraindicated in patients with DS as they may lead to disease aggravation. Cenobamate (CNB) is a novel antiseizure medication (ASM) with promising rates of seizure freedom in patients with focal‐onset, drug‐resistant epilepsy. CNB blocks persistent sodium currents by promoting the inactive states of sodium channels. In a multi‐center study, we analyzed retrospectively the effect of an add‐on therapy of CNB in adult patients with DS. We report four adult patients with DS in whom the use of CNB resulted in a significant seizure reduction of more than 80%, with a follow‐up of up to 542 days. CNB was the first drug in these patients that resulted in a long‐lasting and significant seizure reduction. No severe adverse events occurred. We highlight CNB as an ASM that may lead to a clinically meaningful reduction of seizure frequency in adult patients with DS. It is unclear, however, if all patients with DS benefit, requiring further investigation and functional experiments.