Prediction of melatonin efficacy by pretreatment dim light melatonin onset in children with idiopathic chronic sleep onset insomnia
Research has shown efficacy of melatonin treatment to advance sleep–wake rhythms in insomnia. In healthy adults, direction and magnitude of the phase shift depends on the timing of administration relative to the phase position of the circadian system. Therefore, in the present study we investigated whether in children with chronic sleep onset insomnia (SOI) efficacy of melatonin treatment in the early evening could be predicted from dim light melatonin onset (DLMO), a phase marker of the circadian system. We combined data of two previously published double blind, randomized, placebo-controlled trials in 110 participants, aged 6–12 years. Sleep was actigraphically estimated, and saliva collected, at baseline and in the third week of a 4-week treatment period with 5 mg melatonin or placebo at 18:00 or 19:00 hours. Primary outcome measures were pre- to post-treatment changes in dim light melatonin onset (ΔDLMO), sleep onset (ΔSO), sleep latency (ΔSL), and total sleep duration (ΔTSD). Melatonin advanced DLMO with +1:12 h (P < 0.001), SO with +0:42 h (P = 0.004), SL decreased with 25 min (P = 0.019), and TSD did not change significantly, as compared with placebo. In the melatonin-treated group, but not in the placebo-treated group, pretreatment DLMO was significantly related to ΔDLMO [F(1, 29) = 7.28, P = 0.012] and ΔSO [F(1, 25) = 7.72, P = 0.010]. The time interval between treatment administration and pretreatment DLMO (INT) was only significantly related to ΔSO [F(1,26) = 5.40, P = 0.028]. The results suggest that in children with SOI, the efficacy of early evening melatonin to advance sleep onset and endogenous melatonin onset increases the later the pretreatment DLMO is.
Document Type: Research Article
Affiliations: 1: Department of Child and Adolescent Psychiatry, University of Amsterdam, Amsterdam 2: Centre for Sleep-Wake disorders and Chronobiology, Hospital Gelderse Vallei, Ede 3: Department of Neurology, Epilepsy Centre, Kempenhaeghe, Heeze, The Netherlands
Publication date: June 1, 2005