Table 7.

Melatonin Studies in Children in the United Kingdom (cont.)

Reference	N (age range, yr)	Melatonin Dosage	Duration	Summary/Comments
Neurodevelopmental disorders
Gringras78	146 (3–15)	Doses began at 0.5 mg and were increased every 4 wk to 2, 6, and 12 mg dependent on response; Given 45 min before bedtime	12 wk	Objectively and subjectively, the authors measured sleep time and sleep onset latency. Children fell asleep faster (measured by sleep diaries: approximately −37.5 min and actigraphy approximately −45.3 min). Although melatonin increased total sleep time by 22.4 min, the change was not statistically significant. SEs were similar between both groups, but cough and mood swings were reported more in the placebo group.
Appleton79	110 (3–16)	Doses began with 0.5 mg and could increase based on response to a maximum dose of 12 mg during the first 4 wk. Melatonin was supplied by Alliance Pharma.	12 wk	This trial evaluated total-time sleep time in 146 individuals randomly assigned to receive IR melatonin or placebo. Results were determined via sleep diary and actigraphy. Total sleep time reported via sleep diaries increased from 22.43 to 44.34 min (p = 0.04). A reduction in sleep latency by ~45 min (actigraphy [95% CI, −68.75 to −21.93]; p = 0.0003), and approximately 38 min (sleep diaries [95% CI, −55.27 to −19.71 min]; p < 0.0001). There were no significant differences between groups in SEs. Prior to randomization, 16 children had a diagnosis of seizures of which 13 experienced a seizure during the study with a total of 411 seizures reported. SEs were similar between the 2 groups.
Ross80	46 (1–13)	Children < 5 yr were started on 2.5 and children > 5 yr on 5 mg. Could increase by 2.5 mg to a maximum of 7.5 (<2 yr) or 10 mg (> 2 yr). If children later awoke up to 5mg was permitted as a 2nd dose. Melatonin was supplied by Penn Pharmaceutical.	1 wk of pre-tx, followed by 1 wk of tx with melatonin	Twenty-eight children with a variety of disorders that affects CNS and impacts sleep from an outpatient neurology clinic were included in this study. Observations were made via sleep diaries. An interesting component of this study was organization of sleep problem type and corresponding response to melatonin. For fragmented sleep, 3 participants found melatonin beneficial and 2 did not. For “difficulty settling,” 12 found melatonin beneficial and 2 did not. For “low requirement,” 7 determined benefit, 1 did not. For “awaking” sleep problems, 11 found benefit, 4 did not. For delayed-sleep phase, 2 found melatonin beneficial, 9 did not. Median sleep time premelatonin and postmelatonin was 54 hr and 65.5 hr (p < 0.005). There was a significant difference (p < 0.005) in nighttime sleep premelatonin (53 hr) and postmelatonin (64 hr).

ASD, autism spectrum disorder; IR, immediate release; SE, side effect; tx, treatment