Insomnia Insomnia

176 Attarian
50 years of age who slept normally to another group of subjects who exhibited
actigraphically confirmed decreases in sleep efficiency (12). All 30 received, in
randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3 mg) orally
30 minutes before bedtime for 1 week. Treatments were separated by 1-week washout
periods. Sleep data were obtained by polysomnography on the last 3 nights of
each treatment period. The data demonstrated that the physiological melatonin dose
of 0.3 mg restored sleep efficiency, acting principally in the mid third of the night;
it also elevated plasma melatonin levels to normal. The pharmacologic dose (3 mg),
like the lowest dose (0.1 mg), also improved sleep; however, it induced hypothermia
and caused plasma melatonin to remain elevated into the daylight hours. Although
control subjects, like insomniacs, had low melatonin levels, their sleep was
unaffected by any melatonin dose (12). Melatonin has also been shown to help
aleviate chronic sleep-onset insomnia in children. Smits et al., in the Netherlands,
studied 40 elementary school children, 6 to 12 years of age, who suffered from
chronic sleep-onset insomnia for more than 1 year (13). The study was doubleblind
and placebo-controlled. The children were randomly assigned to receive either
5 mg of melatonin or placebo. The study consisted of a 1-week baseline,
followed by a 4-week treatment period. The study demonstrated that 5 mg of melatonin
taken at 6 PM was relatively safe in the short term and significantly more
effective than placebo in advancing sleep onset and increasing sleep duration in
school children with chronic sleep-onset insomnia (13). Another group in whom
melatonin seems to help alleviate insomnia are people with schizophrenia. Shamir
et al. enrolled 19 subjects who met the DSM–IV criteria for schizophrenia, in a
double-blind, randomized, cross-over, clinically based trial. They were given either
2 mg of controlled release melatonin or placebo for two treatment periods of 3
weeks each with 1-week washouts between treatment periods. Those patients who
had poor sleep at baseline had significant improvement in sleep efficiency with the
melatonin (80%) compared to when they were on placebo (67%). They also had a
significant increase in sleep duration (on average by 45 minutes) and also a significant
reduction in sleep latency (SL) on the average (by 40 minutes) (14). The data
available, however, do not support its use as a wide-spectrum hypnotic. Additionally,
there is little information on its long-term safety (15,16). The reason it seems
to improve sleep in the above mentioned distinct population groups is most likely
based on the fact that they all had low endogenous melatonin, which most primary
insomniacs do not (12,14,17). This is the same theory by which melatonin is thought
to work in circadian rhythm problems. In fact, Stone et al. studied its effects in
healthy volunteers. They compared melatonin given at 11:30 PM and at 8 PM to
temazepam given at similar times. They measured both sleep parameters and core
body temperature. They concluded that melatonin given at 11:30 had no significant
clinical effect on nocturnal sleep in healthy individuals. Hypnotic activity of melatonin,
when given in the early evening (presumably in the absence of endogenous
melatonin), was similar to 20 mg of temazepam (18).