Original articleMelatonin in wake–sleep disorders in children, adolescents and young adults with mental retardation with or without epilepsy: a double-blind, cross-over, placebo-controlled trial
Introduction
Sleep disorders, mainly including increased latency to sleep onset, an increased number and duration of awakenings after sleep onset, reduced sleep efficiency (total sleep time/total sleep time plus waking time after sleep onset), are common in children and adolescents with mental impairment and motor handicap [1], [2]. Such disorders are more frequent when associated with both crypto-symptomatic [3], [4] or idiopathic [5] generalized and partial seizures, that disrupt night-time sleep. Moreover, sleep disturbances were seen with and without the occurrence of seizures during the course of the polygraphic recordings and may not be attributed to recent seizure events. A wake–sleep disorder, on the other hand, contributes significantly per se to worsen both seizure frequency and cognitive-behavioral pattern in these patients.
Among the pharmacologic armamentarium for sleep problems in children, melatonin (MLT), which is a substance naturally produced in the human pineal gland that helps to regulate our sleep–wake cycle through its action on the suprachiasmatic nucleus in the hypothalamus, has raised much interest in recent years. Mostly uncontrolled data are reported in the literature on its efficacy in children without [6], [7] or with developmental disabilities [8], [9], [10], [11], [12] and, to a lesser extent, with epilepsy [13].
The aim of the present study was to verify the clinical efficacy of MLT in children, adolescents and young adults with wake–sleep disorder and mental retardation, most of them on chronic anticonvulsant therapy for epileptic seizures, by means of a randomized, double-blind placebo-controlled trial.
Section snippets
Materials and methods
Patients were enrolled into the study based on the following criteria: (i) mental retardation with/without epileptic seizures; (ii) age more than 12 months, in order to avoid difficulty with calculating infant dosages; (iii) diagnosis of sleep disorder, defined according to the Diagnostic and Statistical Manual of Mental Disorders (DSM), 4th edition (IV) criteria (307,45) as the circadian rhythm sleep disorder [14] including delayed onset of sleep, multiple night awakenings, and short duration
Results
Patients enrolled in the study were 32, of whom 25 completed both MLT and placebo phases. The main characteristics of these patients were: 16 males, nine females, aged from 3.6 to 26 years (mean age 10.5 years), all affected by mental retardation with or without epilepsy. Mental delay was mild in 3 (12%) patients, moderate in 8 (32%), and severe in 14 (56%). Epileptic seizures were present in 18/25 patients (72%); they were complex partial (8), with secondary generalization (5), tonic–clonic
Discussion
In the present randomized controlled study, melatonin was effective in decreasing the time to fall asleep in children with mental disabilities, most of them on antiepileptic drugs for epileptic seizures. This result is very much in keeping with other series relative to young patients affected with developmental disabilities [9], [15]. Similar to other series in which a short-acting preparation of melatonin was employed, in our patients the number of night awakenings did not appear to be
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