Bootsma Hans P, Ricker Lukas, Hekster Yechiel A, Hulsman Jacques, Lambrechts Danielle, Majoie Marian, Schellekens Ad, de Krom Marc, Aldenkamp Albert P
Departments of Neurology, Clinical Neurophysiology, Neuropsychology and Pharmacology of the Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands.
Seizure. 2009 Jun;18(5):327-31. doi: 10.1016/j.seizure.2008.11.006. Epub 2008 Dec 24.
To determine long-term retention, percentage of patients withdrawing because of adverse events, percentage of patients achieving seizure freedom, safety profile of the new anti-epileptic drugs lamotrigine, levetiracetam and topiramate.
All patients treated with lamotrigine, levetiracetam or topiramate in the Epilepsy Centre were identified. Each drug was analyzed from introduction of the drug in the Netherlands up to a final assessment point 2 years later.
Data from 1066 patients were included: 336 for lamotrigine, 301 for levetiracetam, 429 for topiramate. Two-year retention rates were 69.2% (lamotrigine), 45.8% (levetiracetam), 38.3% (topiramate); (LTG vs. LEV at p<0.001; LTG vs. TPM at p<0.001; LEV vs. TPM at p=0.005). Seizure freedom rates were lowest for lamotrigine and highest for levetiracetam. Adverse events played a role in drug discontinuation in 154/429 patients (35.9%) on topiramate, 52/336 patients (15.5%) on lamotrigine (p<0.001), 68/301 patients (22.5%) on levetiracetam (p<0.001). Mood and general CNS-effects are common in patients on lamotrigine and levetiracetam, and neurocognitive side effects are most prevalent in patients on topiramate. A positive effect on cognition is frequently noted in patients on lamotrigine.
A drug that is only modestly efficacious but has a favourable safety profile may look better than a drug that is more efficacious but produces clinically meaningful adverse events. Therefore, a drug's retention rate is mainly determined by its side effect profile. As a consequence, retention rate was highest for lamotrigine and lowest for topiramate. Intermediate retention rates were seen with levetiracetam use.
确定新型抗癫痫药物拉莫三嗪、左乙拉西坦和托吡酯的长期留存率、因不良事件停药的患者百分比、实现无癫痫发作的患者百分比及其安全性。
确定癫痫中心所有接受拉莫三嗪、左乙拉西坦或托吡酯治疗的患者。从每种药物在荷兰引入开始分析，直至2年后的最终评估点。
纳入了1066例患者的数据：拉莫三嗪组336例，左乙拉西坦组301例，托吡酯组429例。两年留存率分别为69.2%（拉莫三嗪）、45.8%（左乙拉西坦）、38.3%（托吡酯）；（拉莫三嗪与左乙拉西坦相比，p<0.001；拉莫三嗪与托吡酯相比，p<0.001；左乙拉西坦与托吡酯相比，p = 0.005）。拉莫三嗪的无癫痫发作率最低，左乙拉西坦最高。不良事件导致托吡酯组154/429例患者（35.9%）停药，拉莫三嗪组52/336例患者（15.5%）停药（p<0.001），左乙拉西坦组68/301例患者（22.5%）停药（p<0.001）。情绪和一般中枢神经系统效应在拉莫三嗪和左乙拉西坦治疗的患者中常见，神经认知副作用在托吡酯治疗的患者中最为普遍。拉莫三嗪治疗的患者经常出现对认知的积极影响。
一种疗效一般但安全性良好的药物可能比一种疗效更好但会产生具有临床意义不良事件的药物看起来更好。因此，药物的留存率主要由其副作用情况决定。结果，拉莫三嗪的留存率最高，托吡酯最低。左乙拉西坦的留存率处于中间水平。
