Tabaee Damavandi Payam, Fabin Natalia, Giossi Riccardo, Matricardi Sara, Del Giovane Cinzia, Striano Pasquale, Meletti Stefano, Brigo Francesco, Trinka Eugen, Lattanzi Simona
Department of Neurology, Fondazione IRCCS San Gerardo dei Tintori, School of Medicine and Surgery, Milan Center for Neuroscience, University of Milano, Bicocca, Monza, Italy.
Laboratory of Epidemiological and Clinical Cardiology, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Neurol Ther. 2023 Apr;12(2):669-686. doi: 10.1007/s40120-023-00452-1. Epub 2023 Feb 28.
Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy.
We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome.
Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73-11.54) and 4.71 (95% CI 0.57-39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33-5.02) and 0.50 (95% CI 0.031-7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89-3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93-14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment.
Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.
芬氟拉明（FFA）是一种苯丙胺衍生物，可促进血清素的释放并阻断其神经元再摄取。FFA最初作为食欲抑制剂引入，也显示出抗癫痫特性。本系统评价旨在评估FFA治疗癫痫患者癫痫发作的疗效和安全性。
我们于2022年6月第3周系统检索了MEDLINE、Cochrane对照试验中央登记库和美国国立卫生研究院临床试验登记库。纳入了关于FFA治疗癫痫且癫痫发作未得到控制患者的随机、双盲或单盲、安慰剂对照研究。疗效指标包括治疗期间基线癫痫发作频率降低≥50%和100%的患者比例。耐受性指标包括因任何原因退出治疗和发生不良事件（AE）的患者比例。根据Cochrane干预措施系统评价手册的建议评估纳入研究的偏倚风险。对每个结局估计风险比（RR）及其95%置信区间（CI）。
共识别出三项试验，总计469例患有德雷维特综合征（DS）和伦诺克斯-加斯东综合征（LGS）的受试者被随机分组。所有三项试验被判定偏倚风险较低。在DS患者中，与安慰剂相比，FFA组惊厥发作频率降低≥50%和100%的RR分别为5.61（95%CI 2.73 - 11.54）和4.71（95%CI 0.57 - 39.30）。在LGS患者中，跌倒发作频率降低≥50%和100%的相应RR分别为2.58（95%CI 1.33 - 5.02）和0.50（95%CI 0.031 - 7.81）。接受FFA和安慰剂治疗的患者中，分别有10.1%和
