A prospective randomized crossover trial investigating melatonin versus sleep deprivation for sleep induction in nap electroencephalography.

Abstract

OBJECTIVE: Electroencephalography (EEG) plays a fundamental role in the diagnosis and classification of epilepsy, and inducing sleep during EEG can improve patient cooperation and enhance the detection of epileptiform activity. Despite its importance, there is currently no standardized approach for sleep induction in pediatric EEG recordings. Consequently, practices such as melatonin administration and sleep deprivation are commonly utilized. This study aimed to compare the effectiveness of 5 mg melatonin versus partial sleep deprivation in inducing sleep during nap-time EEGs in children with epilepsy. METHODS: A randomized crossover trial was conducted involving 33 participants (mean age 14.5 years), each undergoing EEG following either melatonin administration or partial sleep deprivation. In the melatonin arm, participants received an oral dose 30 min before the recording, while in the sleep deprivation arm, sleep was restricted the previous night. The primary outcome was sleep onset latency, defined as the time from relaxation to non-REM stage 2 sleep on EEG. Additionally, melatonin and its metabolite, 6-hydroxy-melatonin, were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: The study showed a mean sleep onset latency of 8.5 min after sleep deprivation and 10.1 min after melatonin administration, with a mean difference of 1.5 min. The analysis of covariance conducted with stratification based on sleep onset latency (five classes) and considering all patients confirmed that melatonin is non-inferior to sleep deprivation in sleep onset latency, with 97.5% lower confidence limits of -0.37. Melatonin levels in the treated group confirmed adequate absorption, while they were undetectable in the sleep-deprived group. SIGNIFICANCE: Melatonin is non-inferior to partial sleep deprivation in reducing sleep onset latency, with comparable diagnostic yield and a favorable tolerability profile. The study demonstrates that 5 mg of melatonin is a safe, effective, and well-tolerated alternative to partial sleep deprivation for sleep induction in pediatric EEG evaluations. Given its ease of use and consistent results, melatonin may be recommended as a practical standard for facilitating EEG recordings in children, particularly those with neurodevelopmental disorders. PLAIN LANGUAGE SUMMARY: This randomized crossover trial evaluated the effectiveness and tolerability of melatonin administered before an EEG recording to induce sleep, compared with partial sleep deprivation. The results showed that melatonin helped children achieve sleep and was non-inferior to sleep deprivation. Moreover, melatonin demonstrated a favorable tolerability profile, representing a safe and easier alternative to support sleep during EEG, particularly in children with neurodevelopmental disorders, and could enhance the efficiency and quality of pediatric EEG recordings.