Sleep Medicine Program, Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Nat Sci Sleep. 2010 May 17;2:85-94. doi: 10.2147/nss.s6680. Print 2010.
Jet lag syndrome (JLS) is a clinical syndrome of disrupted nocturnal sleep and daytime neurocognitive impairment which occurs in the context of rapid transmeridian travel. Many strategies for treatment of JLS exist, and include hypnotics to enhance nocturnal sleep, chronotherapeutic approaches (eg, light therapy, melatonin, or gradual schedule shifting), and alerting agents to counter daytime sleepiness. Safety concerns have prompted renewed interest in managing JLS-associated excessive daytime sleepiness (JLSAEDS). Off-label use of the newer alerting agents modafinil and armodafinil is increasing for this indication, often at the specific request of patients. In order to better evaluate the potential risks and benefits of these medications for the management of JLSAEDS, clinicians must be aware of what is known - and still not known. In this article, the pharmacology and pharmacokinetics of modafinil and armodafinil are reviewed, along with evidence for their efficacy in treating sleepiness associated with narcolepsy, obstructive sleep apnea and shift work sleep disorder. Clinical trial data for use of alerting agents in the management of JLSAEDS are limited to one three-day trial involving armodafinil, dosed in the morning to treat JLSAEDS in the setting of eastbound transmeridian travel. This study showed improvement in objective measures of daytime sleepiness at doses of 50 and 150 mg per day. However, global impression of clinical severity of symptom scores only improved on day 1 for those patients receiving 150 mg, and were otherwise not superior to placebo. Consideration for the use of modafinil or armodafinil for the treatment of sleepiness associated with JLS involves careful integration of patient-reported goals, a review of medical contraindications, and an awareness of rare adverse events. More research is needed in order to identify those who are most likely to benefit from this intervention and better define the risk-benefit ratio for this indication.
时差综合征（JLS）是一种因跨子午线快速旅行而导致夜间睡眠紊乱和日间神经认知障碍的临床综合征。目前有许多治疗 JLS 的策略，包括催眠药来促进夜间睡眠、时间疗法（如光照疗法、褪黑素或逐渐调整作息时间）和提神药物来对抗日间嗜睡。出于安全考虑，人们对管理与 JLS 相关的日间过度嗜睡（JLSAEDS）重新产生了兴趣。出于这一适应证，新型提神药物莫达非尼和阿莫达非尼的超适应证使用正在增加，通常是应患者的具体要求。为了更好地评估这些药物治疗 JLSAEDS 的潜在风险和益处，临床医生必须了解已知的和未知的情况。本文综述了莫达非尼和阿莫达非尼的药理学和药代动力学，以及它们在治疗与发作性睡病、阻塞性睡眠呼吸暂停和轮班工作睡眠障碍相关的嗜睡方面的疗效证据。关于在管理 JLSAEDS 中使用提神药物的临床试验数据仅限于一项涉及阿莫达非尼的为期三天的试验，该试验在向东跨子午线旅行的背景下，在早上使用阿莫达非尼来治疗 JLSAEDS。这项研究显示，在每天 50 毫克和 150 毫克的剂量下，日间嗜睡的客观测量指标有所改善。然而，对于接受 150 毫克治疗的患者，只有在第 1 天，总体临床严重程度症状评分才有所改善，否则与安慰剂相比没有优势。考虑使用莫达非尼或阿莫达非尼治疗 JLS 相关的嗜睡，需要仔细整合患者报告的目标、审查医疗禁忌症，并意识到罕见的不良事件。需要进一步研究，以确定最有可能从这种干预中受益的人群，并更好地定义该适应证的风险效益比。
