Sejal V Jain1, Paul S Horn2, Narong Simakajornboon3, Dean W Beebe4, Katherine Holland5, Anna W Byars5, Tracy A Glauser5. 1. Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: Sejal.Jain@cchmc.org. 2. 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. 3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Pulmonology and Sleep Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 5. Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Abstract
OBJECTIVE: 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. METHODS: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. RESULTS: 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. CONCLUSION: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.
RCT Entities:
OBJECTIVE: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. METHODS: 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. RESULTS: 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. CONCLUSION:SRmelatonin 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.
Authors: Darcy A Krueger; Marguerite M Care; Katherine Holland; Karen Agricola; Cynthia Tudor; Prajakta Mangeshkar; Kimberly A Wilson; Anna Byars; Tarek Sahmoud; David Neal Franz Journal: N Engl J Med Date: 2010-11-04 Impact factor: 91.245
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