Abstract
Objective: To investigate the effect of melatonin treatment on health status and sleep in children with idiopathic sleep-onset insomnia.
Method: A randomized, double-blind, placebo-controlled trial was conducted in a Dutch sleep center, involving 62 children, 6 to 12 years of age, who suffered more than 1 year from idiopathic chronic sleep-onset insomnia. Patients received either 5 mg melatonin or placebo at 7 pm. The study consisted of a 1-week baseline period, followed by a 4-week treatment. Health status was measured with the RAND General Health Rating Index (RAND-GHRI) and Functional Status II (FS-II) questionnaires. Lights-off time, sleep onset, and wake-up time were recorded in a diary, and endogenous dim light melatonin onset was measured in saliva.
Results: The total scores of the RAND-GHRI and FS-II improved significantly more during melatonin treatment compared to placebo. The magnitude of change was much higher in the melatonin group than in the placebo group, with standardized response means for the RAND-GHRI of 0.69 versus 0.07 and for the FS-II of 1.61 versus 0.64. Melatonin treatment also significantly advanced sleep onset by 57 minutes, sleep offset by 9 minutes, and melatonin onset by 82 minutes, and decreased sleep latency by 17 minutes. Lights-off time and total sleep time did not change.
Conclusions: Melatonin improves health status and advances the sleep-wake rhythm in children with idiopathic chronic sleep-onset insomnia. Chronic sleep-onset insomnia occurs in about 10% of the nondisabled school-aged population (Blader et al., 1997) and is associated with increased occurrence of fears, night wakening, and daytime fatigue (Blader et al., 1997; Dahl, 1996; Ring et al., 1998). Poor sleep severely impairs daytime functioning and overall well-being (Dahl, 1996; Wiggs and Stores, 1995) and is associated with impaired health status (Leger et al., 2001; Stein et al., 2001).
Melatonin is a chronobiotic drug with soporific properties (Wirz-Justice and Armstrong, 1996). In adults suffering from delayed sleep phase syndrome, it advances the sleep-wake rhythm (Nagtegaal et al., 1998b) and improves quality of life (Nagtegaal et al., 2000). Jan and colleagues treated more than 100 mentally handicapped children with chronic sleep disorders successfully with 2.5 to 10 mg melatonin (Jan and O'Donnell, 1996).
An earlier study (Smits et al., 2001) showed that melatonin advanced the sleep-wake rhythm and increased sleep duration in elementary school children with idiopathic chronic sleep-onset insomnia. During the follow-up period of that study, many parents reported that their child's behavior had considerably improved. Severe adverse events did not occur.
In children, behavior and the effect of disease on behavior can be assessed with the Functional Status II (FS-II) questionnaire (Stein and Jessop, 1990). General health status can be measured with the RAND General Health Rating Index for children (RAND-GHRI) (Lewis et al., 1989).
Because melatonin seemed to improve behavior in children with chronic sleep-onset insomnia, we performed another placebo-controlled study to assess the influence of melatonin on behavior, health status, and sleep pattern in these children.
