Drug-drug interaction between anti-seizure medications in dravet syndrome and lennox-gastaut syndrome

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. 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. 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.

德雷夫综合征（Dravet syndrome, DS）与伦诺克斯-加斯托综合征（Lennox-Gastaut syndrome, LGS）均为罕见且严重的癫痫性脑病。由于存在耐药性癫痫发作、非癫痫发作相关结局及共病问题，此类疾病的治疗需采用复杂的个体化方案。多药联合治疗是此类疾病管理中不可避免的环节，因此优化药物相互作用（drug-drug interactions, DDIs）的管理，对提升治疗疗效、降低毒性反应并满足患者整体需求至关重要。

本综述探讨了针对DS与LGS患者癫痫发作的现有及新兴药物治疗方案。我们梳理了此类药物与其他抗癫痫药物（antiseizure medications, ASMs）之间已被报道的及理论上存在的药物相互作用，重点关注药代动力学与药效动力学特征。本综述着重强调了此类药物相互作用的临床意义，并给出了相应的临床管理实用建议。

深入理解药物相互作用机制是优化治疗方案的关键，尤其是将具有不同作用机制的抗癫痫药物联合使用时。合理的治疗策略不仅应考虑癫痫发作的控制，还需兼顾患者的共病情况。明确参与药代动力学相互作用的代谢通路，对预测并避免不良反应至关重要。数字化工具与决策支持应用程序可帮助临床医师快速评估药物相互作用，并筛选出最优的药物联合方案。

当前在药物遗传学与精准医学领域开展的研究，为改善DS与LGS等复杂疾病的管理提供了前景，有望催生更优质的个体化治疗策略。