Liverpool Reviews and Implementation Group, Department of Health Data Science, University of Liverpool, Liverpool, UK.
Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
Cochrane Database Syst Rev. 2023 Apr 14;4(4):CD010961. doi: 10.1002/14651858.CD010961.pub2.
Epilepsy is one of the most common neurological disorders. Approximately 30% of people with epilepsy are considered to be drug-resistant, and usually need treatment with a combination of other antiepileptic drugs. Perampanel is a newer antiepileptic drug that has been investigated as add-on therapy for drug-resistant focal epilepsy.
To evaluate the benefits and harms of perampanel as add-on therapy for people with drug-resistant focal epilepsy.
We used standard, extensive Cochrane search methods. The latest search date was 20 October 2022.
We included randomised controlled trials comparing add-on perampanel with placebo.
We used standard Cochrane methods. Our primary outcome was 1. 50% or greater reduction in seizure frequency. Our secondary outcomes were 2. seizure freedom, 3. treatment withdrawal due to any reason, 4. treatment withdrawal due to adverse effects, and 5.
We used an intention-to-treat population for all primary analyses. We presented the results as risk ratios (RR) with 95% confidence intervals (CIs), except for individual adverse effects, which we reported with 99% CIs to compensate for multiple testing. We used GRADE to assess certainty of evidence for each outcome.
We included seven trials involving 2524 participants, all aged over 12 years. The trials were double-blind, randomised, placebo-controlled trials with treatment duration of 12 to 19 weeks. We assessed four trials at overall low risk of bias, and three trials at overall unclear risk of bias, due to risk of detection, reporting, and other biases. Compared with placebo, participants receiving perampanel were more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.67, 95% CI 1.43 to 1.95; 7 trials, 2524 participants; high-certainty evidence). Compared to placebo, perampanel increased seizure freedom (RR 2.50, 95% CI 1.38 to 4.54; 5 trials, 2323 participants; low-certainty evidence) and treatment withdrawal (RR 1.30, 95% CI 1.03 to 1.63; 7 trials, 2524 participants; low-certainty evidence). Participants treated with perampanel were more likely to withdraw from treatment due to adverse effects compared to those receiving placebo (RR 2.36, 95% CI 1.59 to 3.51; 7 trials, 2524 participants; low-certainty evidence). A higher proportion of participants receiving perampanel reported one or more adverse effects when compared to participants who received placebo (RR 1.17, 95% CI 1.10 to 1.24; 7 trials, 2524 participants; high-certainty evidence). Compared with placebo, participants receiving perampanel were more likely to experience ataxia (RR 14.32, 99% CI 1.09 to 188.31; 2 trials, 1098 participants; low-certainty evidence), dizziness (RR 2.87, 99% CI 1.45 to 5.70; 7 trials, 2524 participants; low-certainty evidence), and somnolence (RR 1.76, 99% CI 1.02 to 3.04; 7 trials, 2524 participants). Subgroup analysis indicated that a larger proportion of participants who received perampanel at a dose of 4 mg/day (RR 1.38, 95% CI 1.05 to 1.83; 2 trials, 710 participants), 8 mg/day (RR 1.83, 95% CI 1.51 to 2.22; 4 trials, 1227 participants), or 12 mg/day (RR 2.38, 95% CI 1.86 to 3.04; 3 trials, 869 participants) achieved a 50% or greater reduction in seizure frequency compared to placebo; however, treatment with perampanel 12 mg/day also increased treatment withdrawal (RR 1.77, 95% CI 1.31 to 2.40; 3 trials, 869 participants).
AUTHORS' CONCLUSIONS: Add-on perampanel is effective at reducing seizure frequency and may be effective at maintaining seizure freedom for people with drug-resistant focal epilepsy. Although perampanel was well-tolerated, there was a higher proportion of treatment withdrawals with perampanel compared with placebo. Subgroup analysis suggested that 8 mg/day and 12 mg/day are the most efficacious perampanel doses; however, the use of 12 mg/day would likely increase the number of treatment withdrawals. Future research should focus on investigating the efficacy and tolerability of perampanel with longer-term follow-up, as well as exploring an optimal dose.
癫痫是最常见的神经系统疾病之一。大约 30%的癫痫患者被认为是耐药的，通常需要联合使用其他抗癫痫药物治疗。吡仑帕奈是一种新型抗癫痫药物，已被研究作为耐药性局灶性癫痫的附加治疗药物。
评估吡仑帕奈作为耐药性局灶性癫痫附加治疗的疗效和安全性。
我们使用标准的、广泛的 Cochrane 检索方法。最新检索日期为 2022 年 10 月 20 日。
我们纳入了比较添加吡仑帕奈与安慰剂的随机对照试验。
我们使用标准的 Cochrane 方法。我们的主要结局是 1. 癫痫发作频率减少 50%或更多。我们的次要结局是 2. 无癫痫发作，3. 因任何原因停药，4. 因不良反应停药，和 5. 不良反应。我们对所有主要分析采用意向治疗人群。我们以风险比（RR）和 95%置信区间（CI）表示结果，除了个别不良反应，我们报告了 99%CI 以补偿多次检验。我们使用 GRADE 评估每个结局的证据确定性。
我们纳入了 7 项涉及 2524 名参与者的试验，所有参与者年龄均超过 12 岁。这些试验均为双盲、随机、安慰剂对照试验，治疗持续时间为 12 至 19 周。我们评估了四项试验为总体低偏倚风险，三项试验为总体不确定偏倚风险，原因是检测、报告和其他偏倚的风险。与安慰剂相比，接受吡仑帕奈治疗的患者更有可能达到癫痫发作频率减少 50%或更多（RR 1.67，95%CI 1.43 至 1.95；7 项试验，2524 名参与者；高确定性证据）。与安慰剂相比，吡仑帕奈增加了无癫痫发作（RR 2.50，95%CI 1.38 至 4.54；5 项试验，2323 名参与者；低确定性证据）和停药（RR 1.30，95%CI 1.03 至 1.63；7 项试验，2524 名参与者；低确定性证据）。与接受安慰剂治疗的患者相比，接受吡仑帕奈治疗的患者因不良反应而停药的可能性更高（RR 2.36，95%CI 1.59 至 3.51；7 项试验，2524 名参与者；低确定性证据）。与接受安慰剂治疗的患者相比，接受吡仑帕奈治疗的患者更有可能报告一种或多种不良反应（RR 1.17，95%CI 1.10 至 1.24；7 项试验，2524 名参与者；高确定性证据）。与安慰剂相比，接受吡仑帕奈治疗的患者更有可能出现共济失调（RR 14.32，99%CI 1.09 至 188.31；2 项试验，1098 名参与者；低确定性证据）、头晕（RR 2.87，95%CI 1.45 至 5.70；7 项试验，2524 名参与者；低确定性证据）和嗜睡（RR 1.76，95%CI 1.02 至 3.04；7 项试验，2524 名参与者）。亚组分析表明，接受吡仑帕奈 4 mg/天（RR 1.38，95%CI 1.05 至 1.83；2 项试验，710 名参与者）、8 mg/天（RR 1.83，95%CI 1.51 至 2.22；4 项试验，1227 名参与者）或 12 mg/天（RR 2.38，95%CI 1.86 至 3.04；3 项试验，869 名参与者）治疗的患者癫痫发作频率减少 50%或更多的比例更大；然而，吡仑帕奈 12 mg/天治疗也增加了停药（RR 1.77，95%CI 1.31 至 2.40；3 项试验，869 名参与者）。
添加吡仑帕奈可有效降低癫痫发作频率，可能有助于维持耐药性局灶性癫痫患者无癫痫发作。虽然吡仑帕奈耐受良好，但与安慰剂相比，因不良反应停药的比例更高。亚组分析表明，8 mg/天和 12 mg/天是吡仑帕奈最有效的剂量；然而，使用 12 mg/天可能会增加停药的数量。未来的研究应侧重于长期随访，以调查吡仑帕奈的疗效和耐受性，并探索最佳剂量。
