Zifko Udo A, Rupp Monika, Schwarz Sigrid, Zipko Harald T, Maida Eva M
Rehabilitationsklinik Pirawarth, Bad Pirawarth, Austria.
J Neurol. 2002 Aug;249(8):983-7. doi: 10.1007/s00415-002-0765-6.
Modafinil is a unique wake-promoting agent that is chemically distinct from traditional stimulants. Results of a placebo-controlled study showed it to improve fatigue in multiple sclerosis (MS) at a dose of 200 mg daily, but not at a dose of 400 mg daily.
To establish the efficacy, safety and appropriate dose of modafinil in the treatment of fatigue and sleepiness in patients with multiple sclerosis.
A total of 50 patients diagnosed with MS (mean age 40.4 +/- 10.3 years, 30 females/20 males; MS type: 36 relapsing remitting, 1 primary progressive, 13 secondary progressive; mean disability level 3.8 +/- 1.5 on the Kurtzke EDSS) and complaining of chronic fatigue were enrolled in a prospective 3-month, two-center, open-label study. Efficacy was evaluated with the Fatigue Severity Scale (FSS, score range 0-42), the Epworth Sleepiness Scale (ESS, score range 0-24) and by subjective patient appraisal of change of fatigue, quality of life and overall satisfaction with treatment. Adverse effects (AEs) were recorded throughout the study. Treatment was started with a single daily dose of 100 mg in all patients. In non-responders the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg.
Three patients discontinued modafinil because of AEs (nervousness, dizziness). Two patients (4 %) were treated with 50 mg, 25 (50 %) with 100 mg, 21 (42 %) with 200 mg and 2 (4 %) with 300 mg daily. No patient required 400 mg daily. Mean FSS scores were 30.3 +/- 8.5 at baseline and 25.4 +/- 3.7 at 3 months (p < 0.0001). Mean ESS scores were 9.7 +/- 3.9 at baseline and 4.9 +/- 2.9 at 3 months (p < 0.0001). Self-appraisal of change of fatigue showed clear improvement in 41 patients (87.2 %), some improvement in 4 (8.5 %) and no change in 2 (4.3 %). Overall clinical condition was clearly improved in 43 patients (91.5 %), somewhat improved in 1 patient (2.1 %), and unchanged in 3 patients (6.4 %). No patient reported worsening of overall clinical condition.
Treatment with modafinil significantly improves fatigue and sleepiness and is well tolerated by patients with MS. Unlike the higher dose regimen required in narcolepsy, a low-dose regimen of modafinil is effective in MS.
莫达非尼是一种独特的促醒药物，在化学结构上与传统兴奋剂不同。一项安慰剂对照研究的结果显示，每日服用200毫克剂量的莫达非尼可改善多发性硬化症（MS）患者的疲劳症状，但每日服用400毫克剂量时则无此效果。
确定莫达非尼治疗多发性硬化症患者疲劳和嗜睡症状的疗效、安全性及合适剂量。
共有50例被诊断为MS的患者（平均年龄40.4±10.3岁，女性30例/男性20例；MS类型：复发缓解型36例，原发进展型1例，继发进展型13例；根据库茨克扩展残疾状态量表，平均残疾程度为3.8±1.5）纳入一项为期3个月的前瞻性、双中心、开放标签研究，这些患者均主诉有慢性疲劳症状。采用疲劳严重程度量表（FSS，评分范围0 - 42）、爱泼华嗜睡量表（ESS，评分范围0 - 24）以及患者对疲劳变化、生活质量和治疗总体满意度的主观评估来评价疗效。在整个研究过程中记录不良反应（AE）。所有患者均从每日单次剂量100毫克开始治疗。对于无反应者，剂量每次增加100毫克，直至最大每日剂量400毫克。
3例患者因AE（紧张、头晕）停用莫达非尼。2例患者（4%）每日服用50毫克，25例患者（50%）每日服用100毫克，21例患者（42%）每日服用200毫克，2例患者（4%）每日服用300毫克。没有患者需要每日服用400毫克。基线时平均FSS评分为30.3±8.5，3个月时为25.4±3.7（p < 0.0001）。基线时平均ESS评分为9.7±3.9，3个月时为4.9±2.9（p < 0.0001）。对疲劳变化的自我评估显示，41例患者（87.2%）有明显改善，4例患者（8.5%）有一定改善，2例患者（4.3%）无变化。43例患者（91.5%）的总体临床状况明显改善，1例患者（2.1%）有所改善，3例患者（6.4%）无变化。没有患者报告总体临床状况恶化。
莫达非尼治疗可显著改善MS患者的疲劳和嗜睡症状，且患者耐受性良好。与发作性睡病所需的高剂量方案不同，低剂量的莫达非尼方案对MS有效。
