Ramsay R Eugene, Uthman Basim, Pryor Flavia M, Rowan A James, Bainbridge Jacquelyn, Spitz Mark, Sirven Joseph I, Frederick Tim E
Miami VA Medical Center, Miami, Florida, USA.
Epilepsia. 2008 Jul;49(7):1180-5. doi: 10.1111/j.1528-1167.2008.01584.x.
Pharmacokinetics of antiepileptic drugs (AEDs) can be altered by age-related changes in physiology, thereby altering clinical effects, especially tolerability, in older adults. We compared two dosages of topiramate (TPM) in a pilot study of patients >or=60 years of age with partial-onset seizures.
In this 24-week, double-blind, randomized, parallel-group study, patients with one or more seizures in previous 6 months were randomized to treatment with 50 or 200 mg/day TPM. TPM was initiated as monotherapy or added to one AED and titrated by 25 mg/day per week to target or maximum tolerated dose as the concomitant AED, if any, was withdrawn.
Thirty-eight patients were randomized to the 50 mg/day TPM (mean age, 68 years) and 39-200 mg/day TPM (69 years). Seizure control was similar with the two dosages when TPM could be used as monotherapy, whereas 200 mg TPM was more effective than 50 mg in patients requiring adjunctive therapy. The overall incidence of adverse events was similar for the two dosages--66% with 50 mg and 62% with 200 mg TPM. Most common adverse events were somnolence (TPM 50, 13%; TPM 200, 8%), dizziness (13% vs. 8%), and headache (13% vs. 5%). Of 10 (13%) patients reporting a cognitive-related adverse event, six patients were assigned to the 50-mg group. A total of 14 patients (18%; seven in each group) discontinued TPM due to adverse events.
This pilot study supports the practice of using low-to-moderate dosages of AEDs in older adults.
抗癫痫药物（AEDs）的药代动力学可因生理上与年龄相关的变化而改变，从而改变老年人的临床疗效，尤其是耐受性。在一项针对≥60岁部分性发作患者的初步研究中，我们比较了两种托吡酯（TPM）剂量。
在这项为期24周的双盲、随机、平行组研究中，将过去6个月内有一次或多次发作的患者随机分为接受50或200mg/天TPM治疗组。TPM开始时作为单一疗法或添加到一种AED中，并每周以25mg/天的剂量滴定至目标剂量或最大耐受剂量，若有伴随使用的AED，则将其停用。
38例患者被随机分配至50mg/天TPM组（平均年龄68岁），39例患者被分配至200mg/天TPM组（69岁）。当TPM可作为单一疗法使用时，两种剂量的癫痫控制效果相似，而在需要辅助治疗的患者中，200mg TPM比50mg更有效。两种剂量的不良事件总发生率相似——50mg组为66%，200mg TPM组为62%。最常见的不良事件为嗜睡（50mg TPM组为13%，200mg TPM组为8%）、头晕（13%对8%）和头痛（13%对5%）。在报告有认知相关不良事件的10例（13%）患者中，6例被分配至50mg组。共有14例患者（18%；每组7例）因不良事件停用TPM。
这项初步研究支持在老年人中使用低至中等剂量AEDs的做法。
