Czeisler Charles A, Walsh James K, Roth Thomas, Hughes Rod J, Wright Kenneth P, Kingsbury Lilliam, Arora Sanjay, Schwartz Jonathan R L, Niebler Gwendolyn E, Dinges David F
Division of Sleep Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA 02115, USA.
N Engl J Med. 2005 Aug 4;353(5):476-86. doi: 10.1056/NEJMoa041292.
Patients with shift-work sleep disorder chronically have excessive sleepiness during night work and insomnia when attempting to sleep during the day. We evaluated the use of modafinil for treating sleepiness in patients with this disorder.
In a three-month, double-blind trial, we randomly assigned 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Assessments were performed with the use of the nighttime Multiple Sleep Latency Test, the Clinical Global Impression of Change, the Psychomotor Vigilance Test, diaries of patients, and daytime polysomnography. After randomization, we conducted monthly assessments.
Treatment with modafinil, as compared with placebo, resulted in a modest improvement from baseline in mean (+/-SEM) nighttime sleep latency (the interval between the time a person attempts to fall asleep and the onset of sleep) (1.7+/-0.4 vs. 0.3+/-0.3 minutes, respectively; P=0.002), and more patients had improvement in their clinical symptoms (74 percent vs. 36 percent, respectively; P<0.001). Patients who were receiving modafinil also had a reduction in the frequency and duration of lapses of attention during nighttime testing of their performance on the Psychomotor Vigilance Test (change from baseline, a reduction in lapse frequency of 2.6 vs. an increase of 3.8, respectively; P<0.001), and proportionally fewer patients reported having had accidents or near accidents while commuting home (29 percent vs. 54 percent, respectively; P<0.001). Despite these benefits, patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. Modafinil did not adversely affect daytime sleep as compared with placebo. Headache was the most common adverse event.
Treatment with 200 mg of modafinil reduced the extreme sleepiness that we observed in patients with shift-work sleep disorder and resulted in a small but significant improvement in performance as compared with placebo. However, the residual sleepiness that was observed in the treated patients underscores the need for the development of interventions that are even more effective.
轮班工作睡眠障碍患者长期在夜间工作时极度困倦，而在白天试图睡觉时则出现失眠。我们评估了莫达非尼用于治疗该障碍患者困倦的效果。
在一项为期三个月的双盲试验中，我们将209例轮班工作睡眠障碍患者在每次轮班开始前随机分配，分别给予200毫克莫达非尼或安慰剂。使用夜间多次睡眠潜伏期试验、临床总体印象变化量表、精神运动警觉性测试、患者日记以及白天多导睡眠图进行评估。随机分组后，我们每月进行一次评估。
与安慰剂相比，莫达非尼治疗使平均（±标准误）夜间睡眠潜伏期（从一个人试图入睡到入睡开始的间隔时间）较基线有适度改善（分别为1.7±0.4分钟和0.3±0.3分钟；P = 0.002），且更多患者的临床症状得到改善（分别为74%和36%；P < 0.001）。接受莫达非尼治疗的患者在精神运动警觉性测试夜间表现测试中的注意力不集中频率和持续时间也有所降低（与基线相比的变化，注意力不集中频率分别降低2.6次和增加3.8次；P < 0.001），且在通勤回家时报告发生事故或险些发生事故的患者比例相应减少（分别为29%和54%；P < 0.001）。尽管有这些益处，但接受莫达非尼治疗的患者夜间仍持续存在过度困倦和表现受损的情况。与安慰剂相比，莫达非尼对白天睡眠没有不利影响。头痛是最常见的不良事件。
200毫克莫达非尼治疗减少了我们在轮班工作睡眠障碍患者中观察到的极度困倦，并与安慰剂相比在表现上有小幅但显著的改善。然而，在接受治疗的患者中观察到的残余困倦凸显了开发更有效干预措施的必要性。
