West China Clinical Medical School, West China Hospital, Sichuan University, Chengdu, China.
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China.
Epilepsia Open. 2022 Jun;7(2):271-279. doi: 10.1002/epi4.12574. Epub 2022 Feb 2.
The last decade has seen an increase in the use of anti-seizure medications (ASMs); however, the burden of treating drug-resistant epilepsy has not fallen. We performed this meta-analysis to evaluate the optimal dose of Perampanel (PER) as a new adjunctive treatment for drug-resistant seizures.
We searched for studies published from inception to February 1, 2021 from PubMed, Central Register of Controlled Trials (CENTRAL), and ScienceDirect. Research characteristics, patients' characteristics, and treatment regimen, concomitant ASMs, clinical outcomes were extracted. The practical outcome included a reduction in seizures frequency ≥50%, ≥75%, and ≥100% from baseline convulsive seizure frequency, and the safety outcome included the proportion of drug withdrawal and adverse reactions. Odds ratios (OR) for 95% confidence intervals (95% CI) were estimated by the inverse variance method.
Four trials which enrolled 2187 participants (1569 in the PER group and 618 in the placebo group) were included. Results showed that 8 or 12 mg per day had the best effect on all three outcomes, with no significant difference between 8 and 12 mg per day (≥50% reduction, 35.5% vs 36.1%, P = .84; ≥75% reduction, 17.8% vs 19.1%, P = .64; seizure-free, 3.5% vs 3.7%, P = .85). In addition, 12-mg PER compared to 8 mg had a higher proportion of trial withdrawal (8.7% vs 17.0%; P < .00001) and treatment-emergent adverse event (TEAE) resulting in dose reduction/discontinuation (18.5% vs 32.0%; P < .00001). The adverse events (AEs) significantly associated with adjunctive PER were dizziness, somnolence, fatigue, and irritability.
Adjunctive treatment of PER was associated with a more significant reduction in the frequency of seizures in patients with refractory epilepsy than placebo, but with a higher frequency of AEs. PER at a daily dose of 8 mg appears to have the best ratio between efficacy and tolerance in most study participants.
过去十年，抗癫痫药物（ASMs）的使用有所增加；然而，治疗耐药性癫痫的负担并未减轻。我们进行了这项荟萃分析，以评估作为辅助治疗耐药性癫痫的新型药物吡仑帕奈（PER）的最佳剂量。
我们从 PubMed、CENTRAL 和 ScienceDirect 搜索了从成立到 2021 年 2 月 1 日发表的研究。提取了研究特征、患者特征和治疗方案、伴随的 ASMs、临床结局。实际结局包括与基线抽搐发作频率相比，癫痫发作频率降低≥50%、≥75%和≥100%，安全结局包括停药比例和不良反应。采用逆方差法估计 95%置信区间（95%CI）的优势比（OR）。
纳入了四项试验，共纳入 2187 名参与者（PER 组 1569 名，安慰剂组 618 名）。结果表明，每天 8 或 12 mg 的效果最佳，在所有三个结局方面，8 和 12 mg 之间没有显著差异（≥50%缓解，35.5%比 36.1%，P=0.84；≥75%缓解，17.8%比 19.1%，P=0.64；无发作，3.5%比 3.7%，P=0.85）。此外，与 8 mg PER 相比，12 mg PER 停药比例更高（8.7%比 17.0%；P<0.00001），因不良反应导致剂量减少/停药的比例更高（18.5%比 32.0%；P<0.00001）。与 PER 辅助治疗显著相关的不良反应为头晕、嗜睡、疲劳和易怒。
PER 辅助治疗与安慰剂相比，可显著降低耐药性癫痫患者的癫痫发作频率，但不良反应发生率更高。在大多数研究参与者中，PER 每日 8 mg 的剂量似乎具有最佳的疗效和耐受性比值。
