Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

Psychopharmacology (Berl). 2010 Oct;212(3):379-91. doi: 10.1007/s00213-010-1962-0. Epub 2010 Jul 29.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Actigraphy
  • Child
  • Circadian Rhythm
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Hypnotics and Sedatives / pharmacokinetics
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Melatonin / administration & dosage*
  • Melatonin / pharmacokinetics
  • Melatonin / pharmacology
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Treatment Outcome


  • Hypnotics and Sedatives
  • Melatonin