Abstracts

Rationale: Sleep related comorbidities are common in patients with epilepsy. Sleep onset insomnia is reported in 34% and maintenance insomnia is reported in 54% of the patients with epilepsy. In a retrospective study, 11% of the children with epilepsy, referred for sleep evaluation, had insomnia. Additionally, treatment of some sleep disorders such as obstructive sleep apnea has shown to improve seizure frequency. Melatonin is commonly used as a hypnotic agent in patients with epilepsy. However, limited data exists about its efficacy. We performed a prospective study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Methods: This was a randomized, double-blind, placebo-controlled, cross-over study with sustained release (SR) melatonin at 9 mg dose. Six to eleven years old pre-pubertal children with epilepsy were enrolled. After baseline testing and eligibility determination, subjects were randomized to receive placebo or melatonin for 4 weeks. After 1 week of washout, the subjects who were on placebo received melatonin for the next 4 weeks and vice versa. Outcomes were collected at baseline and at the end of each of the treatment phases. Primary outcomes were sleep latency (SL) and wakefulness after sleep onset (WASO) measured on overnight polysomnography. Other objective outcomes included interictal epileptiform spike density reported as per hour of sleep, which was analyzed on 6 channels EEG from polysomnography. Subjective outcomes included total score on the sleep behavior questionnaire (SBQ) and parent reported seizure frequency. Exact Wilcoxon rank tests were performed using traditional methods for the analysis of cross-over studies. Results: 10 pre-pubertal children with epilepsy were enrolled. Results are summarized in Table 1. SR Melatonin decreased SL (p= 0.02) and WASO (p=0.04) as compared to placebo. No differential cross-over effects were seen. No significant difference was seen in sleep interictal epileptiform spike density and the total score on SBQ. No changes in seizure frequency were seen. No changes were seen in arousal index, N1 and N2 sleep. N3 sleep was significantly increased (p=0.04) and rapid eye movement (REM) sleep was decreased (p=0.01) on melatonin as compared to placebo. Conclusions: This study provides Class 1 evidence that SR melatonin improves sleep latency and WASO. These results indicate that melatonin may be useful in the treatment of insomnia in children with epilepsy. Melatonin does not appear to worsen seizures in children with epilepsy.