Drug-drug interaction between anti-seizure medications in Dravet syndrome and Lennox-Gastaut syndrome.

Abstract

Introduction: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare, severe epileptic encephalopathies requiring complex, individualized treatment due to drug-resistant seizures, non-seizure outcomes, and comorbidities. Polytherapy is an inevitable aspect of managing these conditions, making the management of drug-drug interactions (DDIs) crucial for optimizing efficacy, minimizing toxicity, and addressing broader patient needs.

Areas covered: This review discusses current and emerging pharmacological therapies for seizures in DS and LGS. We explore documented and theoretical DDIs between these drugs and other antiseizure medications (ASMs), focusing on pharmacokinetic and pharmacodynamic characteristics. The clinical significance of these DDIs is emphasized, with practical recommendations for their management.

Expert opinion: Advances in understanding DDIs are key to optimizing treatment, particularly through the combination of ASMs with distinct mechanisms of action. A rational therapeutic approach should consider not only seizure control but also comorbidities. Understanding metabolic pathways involved in pharmacokinetic interactions is essential for predicting and avoiding adverse effects. Digital tools and decision-support apps can assist clinicians in quickly assessing DDIs and selecting the most effective drug combinations. Ongoing research in pharmacogenetics and personalized medicine holds promise for improving the management of complex conditions like DS and LGS, offering potential for better, individualized therapeutic strategies.