Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, 100070 Beijing, China.
Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, China.
Cochrane Database Syst Rev. 2021 May 11;5(5):CD011922. doi: 10.1002/14651858.CD011922.pub4.
Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018.
To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease).
For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies.
We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events.
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data.
We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low.
AUTHORS' CONCLUSIONS: This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.
任何类型的癫痫发作都可能在阿尔茨海默病中观察到。抗癫痫药物似乎可以预防大多数阿尔茨海默病患者癫痫发作的复发。阿尔茨海默病患者的癫痫有药物和非药物治疗方法,但目前没有系统评价来评估这些治疗方法的疗效和耐受性。本综述旨在研究这些不同的方法。这是之前于 2018 年发表的 Cochrane 综述的更新版本。
评估用于治疗阿尔茨海默病(包括散发性阿尔茨海默病和显性遗传性阿尔茨海默病)患者癫痫的药物或非药物干预措施的疗效和耐受性。
对于最新更新,我们于 2020 年 8 月 3 日检索了 Cochrane 研究注册库(CRS Web)和 MEDLINE(Ovid,1946 年至 2020 年 7 月 31 日)。CRS Web 包括来自 PubMed、EMBASE、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台(ICTRP)、Cochrane 对照试验中心注册库(CENTRAL)和 Cochrane 综述组的专门注册库的随机或准随机对照试验,包括 Cochrane 癫痫。为了确定进一步发表的、未发表的和正在进行的试验,我们检索了正在进行的试验登记处、参考文献列表和相关会议记录;我们还联系了试验作者和制药公司。
我们纳入了调查阿尔茨海默病患者癫痫治疗的随机和准随机对照试验,主要结局为无癫痫发作参与者的比例和出现不良事件的参与者的比例。
两名综述作者独立筛选了确定记录的标题和摘要,选择了纳入的研究,提取了数据,交叉核对了数据的准确性,并评估了方法学质量。由于可用数据有限,我们没有进行荟萃分析。
我们纳入了一项关于药物干预的随机对照试验;该试验纳入了 95 名参与者。未发现非药物干预的研究。关于无癫痫发作参与者的比例,在左乙拉西坦与拉莫三嗪(RR)1.20,95%CI 0.53 至 2.71;67 名参与者;极低确定性证据)、左乙拉西坦与苯巴比妥(RR 1.01,95%CI 0.47 至 2.19;66 名参与者;极低确定性证据)或拉莫三嗪与苯巴比妥(RR 0.84,95%CI 0.35 至 2.02;57 名参与者;极低确定性证据)之间无显著差异。似乎左乙拉西坦可以改善认知,拉莫三嗪可以缓解抑郁,而苯巴比妥和拉莫三嗪可以恶化认知,左乙拉西坦和苯巴比妥可以恶化情绪。关于分配、盲法和选择性报告的偏倚风险尚不清楚。我们判断所有结局的证据确定性均为极低。
本综述没有提供足够的证据支持左乙拉西坦、苯巴比妥或拉莫三嗪用于治疗阿尔茨海默病患者的癫痫。关于疗效和耐受性,左乙拉西坦、苯巴比妥和拉莫三嗪之间未发现显著差异。需要进行大型随机对照试验,采用双盲、平行组设计,以确定阿尔茨海默病患者癫痫治疗的疗效和耐受性。