Roth Thomas, Schwartz Jonathan R L, Hirshkowitz Max, Erman Milton K, Dayno Jeffrey M, Arora Sanjay
Henry Ford Sleep Disorders Center, Detroit, MI 48202, USA.
J Clin Sleep Med. 2007 Oct 15;3(6):595-602.
Modafinil is a wake-promoting agent shown to improve wakefulness in patients with excessive sleepiness (hypersomnolence) associated with shift work sleep disorder, obstructive sleep apnea, or narcolepsy. Safety and tolerability data from 6 randomized, double-blind, placebo-controlled studies were combined to evaluate modafinil across these different patient populations.
One thousand five hundred twenty-nine outpatients received modafinil 200, 300, or 400 mg or placebo once daily for up to 12 weeks. Assessments included recording of adverse events and effects of modafinil on blood pressure/heart rate, electrocardiogram intervals, polysomnography, and clinical laboratory parameters.
Two hundred seventy-three patients with shift work sleep disorder, 292 with obstructive sleep apnea, and 369 with narcolepsy received modafinil; 567 received placebo. Modafinil was well tolerated versus placebo, with headache (34% vs 23%, respectively), nausea (11% vs 3%), and infection (10% vs 12%) the most common adverse events. Adverse events were similar across all patient groups. Twenty-seven serious adverse events were reported (modafinil, n = 18; placebo, n = 9). In modafinil-treated patients, clinically significant increases in diastolic or systolic blood pressure were infrequent (n = 9 and n = 1, respectively, < 1% of patients). In the studies, 1 patient in the modafinil group and 1 in the placebo group had a clinically significant increase in heart rate. New clinically meaningful electrocardiogram abnormalities were rare with modafinil (n = 2) and placebo (n = 4). Clinically significant abnormalities in mean laboratory parameters were observed in fewer than 1% of modafinil-treated patients at final visit. Modafinil did not affect sleep architecture in any patient population according to polysomnography.
Modafinil is well tolerated in the treatment of excessive sleepiness associated with disorders of sleep and wakefulness and does not affect cardiovascular or sleep parameters.
莫达非尼是一种促醒药物，已被证明可改善与轮班工作睡眠障碍、阻塞性睡眠呼吸暂停或发作性睡病相关的过度嗜睡（嗜睡症）患者的清醒程度。将来自6项随机、双盲、安慰剂对照研究的安全性和耐受性数据合并，以评估莫达非尼在这些不同患者群体中的情况。
1529名门诊患者接受每日一次200、300或400毫克莫达非尼或安慰剂治疗，最长治疗12周。评估包括记录不良事件以及莫达非尼对血压/心率、心电图间期、多导睡眠图和临床实验室参数的影响。
273名轮班工作睡眠障碍患者、292名阻塞性睡眠呼吸暂停患者和369名发作性睡病患者接受了莫达非尼治疗；567名患者接受了安慰剂治疗。与安慰剂相比，莫达非尼耐受性良好，最常见的不良事件为头痛（分别为34%和23%）、恶心（11%和3%）和感染（10%和12%）。所有患者组的不良事件相似。报告了27起严重不良事件（莫达非尼组18起；安慰剂组9起）。在接受莫达非尼治疗的患者中，舒张压或收缩压出现临床显著升高的情况很少见（分别为9例和1例，<1%的患者）。在研究中，莫达非尼组有1名患者，安慰剂组有1名患者心率出现临床显著升高。使用莫达非尼（2例）和安慰剂（4例）时，新出现的具有临床意义的心电图异常很少见。在最后一次随访时，接受莫达非尼治疗的患者中，平均实验室参数出现临床显著异常的比例不到1%。根据多导睡眠图，莫达非尼在任何患者群体中均未影响睡眠结构。
莫达非尼在治疗与睡眠和觉醒障碍相关的过度嗜睡方面耐受性良好，且不影响心血管或睡眠参数。
