Melatonin 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

Abstract

The aim of the present study was to verify the clinical efficacy of melatonin (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 cross-over trial. Twenty-five patients (16 males, nine females), aged from 3.6 to 26 years (mean 10.5 years), all affected with mental retardation mostly with epileptic seizures, were randomized to oral synthetic fast-release MLT or placebo. Melatonin was initiated at the daily dose of 3 mg, at nocturnal bedtime. In case of inefficacy, MLT dose could be titrated up to 9 mg the following 2 weeks at increments of 3 mg/week, unless the patient was unable to tolerate it. The analysis of all the sleep logs disclosed a significant treatment effect of melatonin on sleep latency (P=0.019). Melatonin was well tolerated in all patients and no side effects were reported. In conclusion, our study supports the efficacy of MLT in young patients with mental disabilities and epileptic seizures in improving the wake–sleep disorders such as time to fall asleep. Overall, MLT appeared to influence the seizure frequency poorly, though there may be occasional seizure worsening or improving. Such a dual effect requires further studies in young epileptic patients.

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.