Lamotrigine add-on therapy for drug-resistant focal epilepsy
藥物耐受型局部癲癇的Lamotrigine附加療法(drug-resistant focal epilepsy)
研究背景
癲癇為一種大腦異常放電、造成發作(Seizure)的疾病。
儘管使用了(舊型)抗癲癇藥物治療(Antiepilepsy Drugs, AEDs), 仍有約3分之1患者經常癲癇發作。此外, 由於現今的AEDs治療仍有許多副作用, 故發展有效的頑固型癲癇新療法非常重要。因此, 一系列新的AEDs被發展為「附加療法」, 而Lamotrigine 為眾多選項的其中之一。
研究目的
本次回顧文獻(review)希望確定Lamotrigine在癲癇發作、副作用、認知功能(理解能力與學習)和生活品質的影響, 並與安慰劑組比較, 用於對現有AEDs無效的局部癲癇附加療法。在本次文獻更新中, 沒有發現新發表的研究要加入討論, 因此結論與前一次回顧相同。
本次回顧文獻收錄14項隨機對照試驗, 共包含1806位受試者。
研究結果
Lamotrigine合併使用其他AEDs, 可更佳的減低藥物耐受型癲癇患者發作頻率。雖然如此, 在常規治療加入Lamotrigine與較高的不良反應比率有關, 例如不穩定(共濟失調,ataxia)、頭暈、複視、噁心嘔吐。
證據品質
我們評估了試驗的偏差風險, 整體來說這些風險為低、或不明確的。而關於證據品質, 我們評價為高到中等可信度。
研究結論
需要進一步的高質量研究,以全面評估Lamotrigine的療效和耐受性,並將Lamotrigine與其他新型AED進行比較。證據收錄截至2020年3月9日。
Reference
----------其他文章--------------------
Background
This is an updated version of the Cochrane Review previously published in 2016.
Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs. Lamotrigine, in combination with other antiepileptic drugs (add‐on), can reduce seizures, but with some adverse effects.
Objectives
To determine the effects of lamotrigine on (1) seizures, (2) adverse‐effect profile, and (3) cognition and quality of life, compared to placebo, when used as an add‐on treatment for people with drug‐resistant focal epilepsy.
Search methods
For the latest update of the review, we searched the following databases on 9 March 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 06, 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 Epilepsy. No language restrictions were imposed.
Selection criteria
Randomised placebo‐controlled trials of people with drug‐resistant focal epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double‐, single‐ or unblinded, placebo‐controlled. For cross‐over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug‐resistant focal epilepsy.
Data collection and analysis
For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention‐to‐treat. Sensitivity best‐ and worse‐case analyses were undertaken to account for missing outcome data. Pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, we calculated pooled RRs and 99% Cls.
Main results
We did not identify any new studies for this update, therefore, the results and conclusions are unchanged.
In previous updates of this review, the authors found five parallel add‐on studies, eight cross‐over studies in adults or children with drug‐resistant focal epilepsy, and one parallel add‐on study with a responder‐enriched design in infants. In total, these 14 studies included 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks; treatment phases from eight to 36 weeks. Overall, 11 studies (1243 participants) were rated as having low risk of bias, and three (697 participants) had unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in four studies (563 participants).
The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate‐certainty evidence) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate‐certainty evidence). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia (double vision), and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 trials; 1525 participants; high‐certainty evidence); dizziness 2.00 (99% Cl 1.52 to 2.64;13 trials; 1768 participants; moderate‐certainty evidence); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 trials, 944 participants; high‐certainty evidence); nausea 1.81 (99% Cl 1.22 to 2.68; 12 studies,1486 participants; moderate‐certainty evidence). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate certainty, due to incomplete data for some outcomes.
Authors' conclusions
Lamotrigine as an add‐on treatment for drug‐resistant focal seizures appears to be effective in reducing seizure frequency, and seems to be fairly well‐tolerated. However, the trials were of relatively short duration and provided no evidence for the long term. Further trials are needed to assess the long‐term effects of lamotrigine, and to compare lamotrigine with other add‐on drugs.
留言列表
