Add-On Melatonin Improves Sleep Behavior in Children With Epilepsy: Randomized, Double-Blind, Placebo-Controlled Trial

Madhur Gupta MD; Satinder Aneja MD; Kamlesh Kohli, MD


J Child Neurol. 2005;20(2):112-115. 

In This Article

Abstract and Introduction

This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire. Of the 31 patients, 16 randomly received add-on melatonin, whereas 15 received add-on placebo. The questionnaire showed good internal consistency in our patient population (Cronbach's α = .83). The percentage decrease in the median total sleep score was 24.4 (range 0.0-34.9) in the valproate + melatonin group compared with 14.0 (range -2.2-18.8) in the valproate + placebo group, the difference being statistically significant ( P < .05). The median percentage decrease in the parasomnias score was 60 (range 0.0-70.8) in the valproate + melatonin group compared with 36.4 (range 0.0-63.2) in the valproate + placebo group, the difference being statistically significant (P < .05). There was no significant difference between the percentage decrease in the daytime drowsiness scores and sleep fragmentation scores. Parent-child interaction subscale scores were not significantly different between age groups. The age at onset of seizures and the type of seizures did not correlate significantly to the total sleep scores. Given that sleep problems are known to complicate epilepsy, add-on melatonin, which has a wide safety window, can be of promise in the pharmacotherapy of pediatric epilepsy.

Studies on sleep problems in children with epilepsy are promising but limited. Zaiwalla and Stores found a generally higher rate of severe and persistent sleep problems, especially sleeplessness, daytime lethargy, and unrefreshing sleep, in children with epilepsy.[1] In a parental questionnaire study, they investigated the sleep problems and daytime behavior of schoolchildren with mild forms of epilepsy. Compared with normal controls, children with epilepsy showed a higher rate of sleep problems and disturbed daytime behavior.[1] Chronic sleep disorders can affect the child's development adversely because sleep plays a major role in the early maturational processes in the brain.[2] Sleep deprivation leads to reduced attention span, low frustration threshold, mood changes, impaired social interactions, and difficulties with memory formation and recall.[3] There is an association of epilepsy being exacerbated by sleep deprivation.[4] Sleep disorders have also been reported to resemble seizures.[5] Some children with incompletely controlled epilepsy experience fewer seizures following melatonin treatment once they are no longer sleep deprived.[6] There is evidence that children often reveal cognitive, emotional, and behavioral manifestations of inadequate sleep without showing frank sleepiness.[7]

Antiepileptic drugs might also affect sleep patterns differentially. Patients on valproate monotherapy have been shown to have some impairment in attention, with increased daytime sleepiness.[8] Valproic acid, a γ-aminobutyric acid (GABA)ergic drug, has been found to suppress nocturnal plasma melatonin levels in young, healthy adults, suggesting increased sleep problems in these patients owing to the drug's action on endogenous melatonin synthesis.[9]

In the last decade, much interest in melatonin has arisen. Melatonin helps regulate sleep-wake cycles through its action on the suprachiasmatic nucleus in the hypothalamus. Melatonin (5-methoxy- N -acetyltryptamine), a pineal hormone, has been extensively tried in the treatment of sleep-wake cycle disorders.[10] However, melatonin treatment has been studied mostly in uncontrolled trials. Therefore, a randomized, double-blind, placebo-controlled trial was conducted on epileptic children to assess the effects of add-on melatonin administration on sleep problems in epileptic children on valproate monotherapy.


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