Jain Sejal V, Horn Paul S, Simakajornboon Narong, Beebe Dean W, Holland Katherine, Byars Anna W, Glauser Tracy A
Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Sleep Med. 2015 May;16(5):637-44. doi: 10.1016/j.sleep.2015.01.005. Epub 2015 Jan 21.
Insomnia, especially maintenance insomnia, is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, crossover study to identify the effects of melatonin on sleep and seizure control in children with epilepsy.
Eleven prepubertal, developmentally normal children aged 6-11 years with epilepsy were randomized by a software algorithm to receive placebo or a 9-mg sustained release (SR) melatonin formulation for four weeks, followed by a one-week washout and a four-week crossover condition. The pharmacy performed blinding; patients, parents, and study staff other than a statistician were blinded. The primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. The secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on electroencephalogram (EEG), and reaction time (RT) measures on psychomotor vigilance task (PVT). Statistical tests appropriate for crossover designs were used for the analysis.
Data were analyzed from 10 subjects who completed the study. Melatonin decreased sleep latency (mean difference, MD, of 11.4 min and p = 0.02) and WASO (MD of 22 min and p = 0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, slow-wave sleep duration and rapid eye movement (REM) latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin.
SR melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed, but the study was too small to allow any conclusions to be drawn in this regard.
失眠，尤其是维持性失眠，在癫痫患者中广泛存在。尽管褪黑素被广泛使用，但其疗效相关数据有限。我们进行了一项随机、双盲、安慰剂对照、交叉研究，以确定褪黑素对癫痫患儿睡眠和癫痫控制的影响。
11名6至11岁青春期前发育正常的癫痫患儿通过软件算法随机分组，接受安慰剂或9毫克缓释（SR）褪黑素制剂治疗四周，随后为期一周的洗脱期，接着进行四周的交叉治疗。药房负责设盲；患者、家长以及除统计人员外的研究人员均不知情。主要结局指标为多导睡眠图测量的入睡潜伏期和睡眠起始后觉醒时间（WASO）。次要结局指标包括癫痫发作频率、脑电图（EEG）每小时睡眠中癫痫样棘波密度以及精神运动警觉任务（PVT）的反应时间（RT）测量值。采用适用于交叉设计的统计检验进行分析。
对完成研究的10名受试者的数据进行了分析。与安慰剂相比，褪黑素缩短了入睡潜伏期（平均差值，MD，为11.4分钟，p = 0.02）和WASO（MD为22分钟，p = 0.04）。未观察到棘波密度或癫痫发作频率恶化。此外，褪黑素使慢波睡眠时间和快速眼动（REM）潜伏期增加，REM睡眠时间减少。这些变化具有统计学意义。一名偏头痛患儿在服用褪黑素时出现头痛加重。
SR褪黑素在统计学上显著缩短了入睡潜伏期和WASO。未观察到对癫痫发作有明显影响，但该研究规模过小，无法就此得出任何结论。
