Anderson Gail D, Hakimian Shahin
Department of Pharmacy and Regional Epilepsy Center, University of Washington, Seattle, WA, 98195, USA.
Department of Neurology and Regional Epilepsy Center, University of Washington, Seattle, WA, 98195, USA.
Drugs Aging. 2018 Aug;35(8):687-698. doi: 10.1007/s40266-018-0562-2.
The incidence of epilepsy is highest in the older adult age group. Seizures in older adults can be more difficult to diagnose because their presentation is often subtle and can easily be mistaken for other conditions. Fortunately, new-onset epilepsy in the older adult is often pharmaco-responsive, with as many as 80-85% of patients achieving remission, often with monotherapy at modest doses. Many physiological and pathological changes occur with aging that can alter the pharmacokinetics of antiseizure drugs (ASDs). For the majority of the old- and new-generation ASDs, a decrease in dose may be needed to maintain concentrations equivalent to those found in young adults. The risk of drug interactions with ASDs is substantial, as polypharmacy is common. The first-generation ASDs (carbamazepine, phenytoin, phenobarbital, and valproic acid) have the potential to interact with many drugs, but many newer ASDs either do not have significant interactions or are selective inhibitors and inducers of specific hepatic enzymes. The differences in adverse effects between younger and older adults are not just due to dosing and pharmacokinetics. Older adults are more susceptible to the gait, balance, and cognitive effects of ASDs. Overall, the improved tolerability and decreased drug interaction potential of the newer-generation ASDs, such as lamotrigine and levetiracetam, have demonstrated their superiority in the treatment of seizures in older adults and, as such, are clearly favored for new-onset epilepsy in older adults.
癫痫发病率在老年人群体中最高。老年人的癫痫发作可能更难诊断,因为其表现往往较为隐匿,很容易被误诊为其他病症。幸运的是,老年人新发癫痫通常对药物有反应,多达80% - 85%的患者可实现缓解,通常采用小剂量单药治疗。随着年龄增长会出现许多生理和病理变化,这些变化会改变抗癫痫药物(ASD)的药代动力学。对于大多数新一代和老一代ASD,可能需要降低剂量以维持与年轻人相当的血药浓度。由于联合用药很常见,ASD发生药物相互作用的风险很大。第一代ASD(卡马西平、苯妥英、苯巴比妥和丙戊酸)有可能与许多药物相互作用,但许多新一代ASD要么没有显著的相互作用,要么是特定肝酶的选择性抑制剂和诱导剂。年轻人和老年人在不良反应上的差异不仅仅是由于给药和药代动力学。老年人更容易受到ASD对步态、平衡和认知方面的影响。总体而言,新一代ASD(如拉莫三嗪和左乙拉西坦)具有更好的耐受性和更低的药物相互作用可能性,已证明它们在治疗老年人癫痫发作方面的优越性,因此显然更适合用于老年人新发癫痫的治疗。