Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT.
Study Goal
The researchers aimed to establish a dose-response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children with chronic sleep onset insomnia (CSOI).
Results Summary
Melatonin significantly advanced SO and DLMO by approximately 1 hour and decreased SOL by 35 minutes, with no dose-response relationship found within the 0.05-0.15 mg/kg range. The effect increased with earlier circadian time of administration.
Population
Children aged 6-12 years with chronic sleep onset insomnia (n=72).
Effective Dosage
0.05, 0.1, and 0.15 mg/kg melatonin administered once daily.
Duration
1 week.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin | increase | sleep onset (SO) | children between 6 and 12 years with chronic sleep onset insomnia (CSOI) | approximately 1 h | significantly advanced | #1 |
melatonin | increase | dim light melatonin onset (DLMO) | children between 6 and 12 years with chronic sleep onset insomnia (CSOI) | approximately 1 h | significantly advanced | #2 |
melatonin | decrease | sleep onset latency (SOL) | children between 6 and 12 years with chronic sleep onset insomnia (CSOI) | 35 min | decreased | #3 |
melatonin 0.05, 0.1, and 0.15 mg/kg | no change | sleep onset (SO), sleep onset latency (SOL), and dim light melatonin onset (DLMO) | children with CSOI | no significant change | effect size was not different | #4 |
melatonin | decrease | dim light melatonin onset (DLMO) | - | r (s) = -0.33, p = 0.022 | correlated significantly with treatment effect | #5 |
melatonin | decrease | sleep onset (SO) | - | r (s) = -0.38, p = 0.004 | correlated significantly with treatment effect | #6 |
melatonin | decrease | sleep onset (SO) shift | - | r = -0.35, p = 0.006 | was correlated with | #7 |
melatonin | increase | sleep onset (SO), sleep onset latency (SOL), and dim light melatonin onset (DLMO) | - | - | increases with an earlier circadian time of administration | #8 |
melatonin | increase | soporific effects | - | - | enhance the sleep onset shift | #9 |
melatonin | increase | treatment of CSOI | children | in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime | is effective | #10 |
RATIONALE: Pharmacokinetics of melatonin in children might differ from that in adults. OBJECTIVES: This study aims to establish a dose-response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI). METHODS: The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n = 72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL. RESULTS: Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (r (s) = -0.33, p = 0.022) and SO (r (s) = -0.38, p = 0.004), whereas clock TOA was correlated with SO shift (r = -0.35, p = 0.006) and not with DLMO shift. CONCLUSIONS: No dose-response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05-0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime.