Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial.

To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to receive either 5-mg melatonin or placebo. The study consisted of a 1-week baseline, consecutively followed by a 4-week treatment period. After that period, treatment was continued if the parents wished so. The study's impact was assessed by measurements of lights-off time, sleep onset, and wake-up time, recorded in a diary (n = 33). Sleep onset was also recorded with an actigraph (n = 25). Endogenous dim light melatonin onset was measured in saliva (n = 27). Sustained attention was evaluated with the Bourdon-Vos reaction time test (n = 36). In the melatonin group, mean (95% CI) lights-off time advanced 34 (6-63) minutes, diary sleep onset 63 (32-94) minutes, actigraphic sleep onset 75 (36-114) minutes, and melatonin onset 57 (24 to 89) minutes; total sleep time increased 41 (19-62) minutes. In the placebo group, these parameters did not shift significantly. The change during the 4-week treatment period differed between the treatment groups significantly as to lights-off time, diary and actigraphic sleep onset, sleep duration, and melatonin onset. There were no significant differences between the treatment groups in the change of sleep latency, wake-up time, and sustained attention reaction times. Mild headache occurred in 2 children during the first 2 days of the melatonin treatment. Eighteen months after the start of the trial, in 13 of the 38 children who could be followed up, melatonin treatment was stopped because their sleep problem was solved and in 1 child because sleep was not improved. Twelve children used melatonin 5 mg, the other 1.0 to 2.5 mg. One child developed mild generalized epilepsy 4 months after the start of the trial. The results show that melatonin, 5 mg at 6 PM, was relatively safe to take in the short term and significantly more effective than placebo in advancing sleep onset and dim light melatonin onset and increasing sleep duration in elementary school children with chronic sleep onset insomnia. Sustained attention was not affected.

Correlation between concentrations of melatonin in saliva and serum in patients with delayed sleep phase syndrome.

Exogenous melatonin, which can be used to treat certain circadian rhythm disorders, maximally advances delayed rhythms when administered 5 hours before the endogenous melatonin starts to increase. The time of the start of the endogenously melatonin is defined as Dim Light Melatonin Onset (DLMO). The DLMO concentration has been defined in serum to be 10 pg/ml. Because of the greater practicability of frequent saliva sampling over blood sampling, we have validated radioimmunoassay (RIA) measurements of melatonin in saliva in patients diagnosed as suffering from a typical circadian rhythm disorder: Delayed Sleep Phase Syndrome (DSPS). Based on these results we have defined the equivalent salivary DLMO concentration to be 4 pg/ml.

Comparison between regional myocardial perfusion reserve and coronary flow reserve in the canine heart.

Diameter stenosis and flow reserve are indices of morphological and functional severity of coronary artery stenosis. Flow reserve can be determined at coronary arterial or at myocardial level. In the presence of functional collateral circulation, coronary flow reserve and myocardial perfusion reserve may differ. We studied coronary flow, coronary flow reserve and myocardial perfusion reserve in an open chest dog model with intact collateral circulation, before and after induction of coronary artery stenosis. Coronary flow was determined with perivascular ultrasonic flow probes and myocardial perfusion reserve from digital angiographic images, in the stenotic as well as the adjacent non-stenotic coronary arteries. Before induction of a stenosis, a significant correlation existed between coronary flow reserve and myocardial perfusion reserve of the left anterior descending (r = 0.59; P < 0.005) and the left circumflex arteries (r = 0.84, P < 0.005). In stenotic arteries, coronary flow reserve and myocardial perfusion reserve decreased significantly (P < 0.005), but in the adjacent non-stenotic arteries coronary flow reserve was not affected. Myocardial perfusion reserve in the non-stenotic adjacent left anterior descending artery decreased significantly (P < 0.05) and no correlation was found between coronary flow reserve and myocardial perfusion reserve, whereas in the adjacent non-stenotic left circumflex artery there was no statistically significant decrease (4.1 +/- 1.6 --> 3.5 +/- 1.4) but there was a good correlation between coronary flow reserve and myocardial perfusion reserve (r = 0.85; P < 0.005). This study demonstrates that, in the presence of a stenosis and functioning collateral circulation, coronary flow reserve is not a reliable predictor of myocardial perfusion reserve; both parameters provide mutually complementary information.