Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT - PubMed (original) (raw)

Randomized Controlled Trial

. 2010 Oct;212(3):379-91.

doi: 10.1007/s00213-010-1962-0. Epub 2010 Jul 29.

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Randomized Controlled Trial

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

Ingeborg M van Geijlswijk et al. Psychopharmacology (Berl). 2010 Oct.

Abstract

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.

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Figures

Fig. 1

Fig. 1

Randomization scheme and justification of obtained outcome data (per group actigraphy and DLMO data obtained within the same group of included participants)

Fig. 2

Fig. 2

a DLMO (threshold = 4 pg/ml) advance (individual differences between baseline and treatment week) in the four treatment groups. b SO shift (individual differences between baseline and treatment week) in the four treatment groups. c SOL reduction (individual differences baseline and treatment week) in the four treatment groups. Solid box upper and lower quartiles, box length contains the middle 50% of the data (IQR); line median, lines extending from box (whiskers) the distance to the largest and smallest observations that are less than one quartile range from the box, dots O outliers (>1.5 × IQR) × = extremes (>3 × IQR). DLMO dim light melatonin onset, SO sleep onset, SOL sleep onset latency

Fig. 3

Fig. 3

a DLMO, SO, and SOL shifts with clock TOA in the three melatonin-treatment groups. b DLMO, SO, and SOL shifts with circadian TOA in the three melatonin-treatment groups

Fig. 4

Fig. 4

DLMO, SO, and SOL shifts with PAD in the three melatonin-treatment groups

Fig. 5

Fig. 5

a DLMO shift (individual differences between baseline and treatment week) with TOA related to baseline DLMO, for all groups, plotted on top of a 24-h phase response curve adapted from Burgess et al. (2008). b SO shift (individual differences between baseline and treatment week) with TOA related to baseline DLMO in all treatment groups

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