Pediatric Neurology Section, Department of Neurology, University of Wisconsin, Madison, Wisconsin, USA.
Curr Opin Neurol. 2010 Apr;23(2):157-63. doi: 10.1097/WCO.0b013e32833735b5.
The aim is to review rational polytherapy of antiepileptic drugs in terms of conventional and novel mechanisms of action, consider combinations that might be beneficial when used as polytherapy, and discuss whether animal models can predict clinical efficacy.
Many patients with epilepsy require concurrent treatment with more than one antiepileptic drug (rational polytherapy), but there is little information available as to which drugs might work best in combination. Conventional antiepileptic drugs act by blocking sodium channels or enhancing gamma-aminobutyric acid function. Some newer antiepileptic drugs have novel mechanisms of action, including impairment of the slow inactivation of sodium channels, binding to the presynaptic vesicle protein SV2A, binding to the calcium channel alpha2delta subunit, and opening select potassium channels. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Quantitative techniques such as isobolography can be used to compare the efficacy and side effects of antiepileptic drug combinations in animals. However, neither such methods nor antiepileptic drug mechanisms of action have yet proven useful in predicting clinical benefit in patients.
Animal models can be used to help predict drug combinations that might be effective clinically, based on novel mechanisms of action. However, at this point, antiepileptic drug choice in patients with epilepsy remains empirical.
本文旨在从传统和新作用机制的角度来回顾抗癫痫药物的合理联合治疗，考虑可能作为联合治疗有益的组合，并讨论动物模型是否可以预测临床疗效。
许多癫痫患者需要同时使用多种抗癫痫药物（合理的联合治疗），但关于哪些药物联合使用可能效果最好的信息却很少。传统的抗癫痫药物通过阻断钠通道或增强γ-氨基丁酸功能起作用。一些新的抗癫痫药物具有新的作用机制，包括损害钠通道的缓慢失活、与突触前囊泡蛋白 SV2A 结合、与钙通道 α2δ亚基结合以及打开选择性钾通道。一些抗癫痫药物具有多种或不确定的作用机制。定量技术，如等辐射分析法，可用于比较动物中抗癫痫药物组合的疗效和副作用。然而，这些方法和抗癫痫药物的作用机制都尚未在预测患者的临床获益方面证明有用。
动物模型可用于帮助预测基于新作用机制的临床有效药物组合。然而，在这一点上，癫痫患者的抗癫痫药物选择仍然是经验性的。
