Table 6.
Melatonin Studies in Children in the European Union (Countries Include Netherlands) (cont.)
| Study | N (age range, yr) | Melatonin Dosage | Duration | Summary/Comments |
|---|---|---|---|---|
| Insomnia | ||||
| Smits71 | 33 (6–12) | 5 mg at 1800, adjusted to results. Melatonin was provided from Helsinn Chemicals. |
5 wk (1-wk baseline, 4 wk tx) | Children were randomly assigned to receive either melatonin or placebo for 4 wk but could continue post study. Actigraphy and sleep diaries/determine sleep onset and DLMO was measured via saliva. Lights off time improved by about 40 min based on diary responses in the melatonin group (p = 0.035) but did not change in the placebo group. Sleep onset evaluated via actigraphy also changed significantly with an approximate 1 hr of improvement from baseline in the melatonin group (p = 0.005) and a worsening of onset in the placebo group. DLMO and sleep onset, using diary reports and actigraphy, did not correlate. Transient headache at initiation of melatonin (n = 2) and new onset epilepsy (n = 1) were reported. |
| Braam72 | 58 (1–58) | 5 mg at 1900 for those ≥6, 2.5 mg at 1800 for those <6 yr. Melatonin was supplied by Duchefa Farma BV. |
5 wk (1-wk baseline, and 4 wk tx) | Participants were randomly assigned melatonin or placebo after 1 wk of baseline. The melatonin group experienced significantly shorter sleep onset time (~34 min, p = 0.005), decreased sleep latency (~30 min, p = 0.002), increased sleep time (~48 min, p = 0.032), and less time awake during the night (42% improvement, p = 0.012). SEs in the melatonin group were included restlessness (n = 5), daytime crying (n = 5), decreased appetite (n = 5), and restless legs (n = 1). |
| Neurodevelopmental disorders | ||||
| Braam73 | 49 (4–78) | <6 yr received 2.5 mg at 1800, >6 yr received 5 mg at 1900 Melatonin was supplied by Duchefa Farma BV. |
4 wk tx with a 1-wk washout period | Includes adults and children with intellectual disabilities experiencing chronic insomnia. About 33% were over 20 yr. Outcome measures were Maladaptive Behavior Scale for the Mentally Retarded (SGZ) scores (components: SGZ-A, aggressive maladaptive behavior; SGZ-V, verbal aggressive behavior; SGZ-Z, mixed maladaptive behavior; SGZ-T scores from SGZ-A, SGZ-V, and SGZ-M that reflects the overall severity of challenging behavior), time lights went out, sleep latency, total sleep time, and number and duration of night wakes. Statistical significance in change/improvement was determined for SGZ-M (p = 0.003), SGZ-T (p = 0.005), sleep latency (−34 minutes, p < 0.001), decrease in wake time (0.66, p = 0.002), and total sleep time (increased by ~34 minutes, p = 0.043). Limitation: inclusion of adults may not be clinically applicable to children. |
| De Leersnyder74 | 88 (6–12) | 4 mg of PR if body weight < 40 kg. If > 40 kg then 6 mg Circadin produced by Neurim Pharmaceuticals. | 6–72 mo | Questionnaire results used to determine sleep quality, mood, and onset. PR melatonin increased sleep duration (10.1%, p < 0.001), improved quality of sleep (75%, p < 0.001), decreased sleep latency (44.0%, p < 0.001), and the number of awakenings (75%, p < 0.001). Daytime somnolence was reported (n = 2). Other SEs were mild, but specifics not provided. Limitation: no placebo group. |
ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CBT, cognitive-behavioral therapy; CR, controlled release; CSOI, chronic sleep onset insomnia; DLMO, dim light melatonin onset; FR, fast release; IR, immediate release; PR, prolonged release; SE, side effect; tx, treatment