Effects of a Low Dose of Melatonin on Sleep in Children with Angelman Syndrome

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Abstract
The effects of low dose melatonin therapy on sleep behavior and serum melatonin levels were studied in Angelman syndrome (AS) children suffering from insomnia. 24-hour motor activity was monitored in 13 AS children (age 2-10 yr) in their home environments for 7 days prior to melatonin treatment and for 5 days during which a 0.3 mg dose of melatonin was administered daily 0.5-1 hour before the patient's habitual bedtime. Blood samples were with-drawn at hourly intervals over two 21-hour periods in order to measure individual endogenous serum melatonin levels and the levels induced by melatonin treatment. Actigraphic recording of motor activity, confirmed by parents' reports, showed a significant improvement in the patients' nocturnal sleep pattern as a result of melatonin treatment. Analysis of the group data revealed a significant decrease in motor activity during the total sleep period following melatonin treatment, and an increase in the duration of the total sleep period. Endogenous peak nocturnal melatonin values ranged from 19 to 177 pg/ml. The administration of melatonin elevated peak serum hormone levels to 128-2800 pg/ml in children of different ages and body mass. These data suggest that a moderate increase in circulating melatonin levels significantly reduces motor activity during the sleep period in Angelman syndrome children, and promotes sleep.