The Efficacy and Safety of the Melatonin Agonist beta-Methyl-6-Chloromelatonin in Primary Insomnia: A Randomized, Placebo-Controlled, Crossover Clinical Trial
J Clin Psychiatry 2005;66(3):384-390
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Background: While melatonin agonists are known
to regulate circadian sleep rhythms, it is not clear whether
melatonin agonists have a direct soporific effect. It has been
suggested that melatonin's soporific effect is secondary to its
ability to induce hypothermia. beta-Methyl-6-chloromelatonin is a
high-affinity melatonin receptor agonist that is not associated
with hypothermia. The purpose of the present study was to
determine if the melatonin agonist beta-methyl-6-chloromelatonin has
a direct soporific effect in subjects with primary insomnia.
Method: A double-blind, placebo-controlled,
crossover safety and efficacy study of 20 mg, 50 mg, and 100 mg
of beta-methyl-6-chloromelatonin and placebo was conducted in
subjects with DSM-IV-TR primary insomnia. Of 84 subjects
screened, 40 progressed to randomly receive each of 3
beta-methyl-6-chloromelatonin doses or placebo on each of 2
consecutive nights with 5-day washout periods between treatments.
The effect of treatment on both polysomnographic and subjectively
measured sleep parameters, next-morning psychomotor performance,
and safety measures was determined. The primary outcome measure
was latency to persistent sleep measured by polysomnography.
Results: A significant effect of
beta-methyl-6-chloromelatonin on the primary efficacy variable,
latency to persistent sleep, was observed (p = .0003). The 20-mg
dose resulted in a significant 31% improvement in sleep latency
compared with placebo, while significant 32% and 41% improvements
were observed at the 50-mg and 100-mg doses, respectively (20 mg,
p = .0082; 50 mg, p = .0062; 100 mg, p < .0001). Similarly, a
significant effect of beta-methyl-6-chloromelatonin on subjective
measures of time to fall asleep occurred (p = .0050), with
significant improvement observed at both the 50-mg and 100-mg
doses (p = .0350 and .0198, respectively) and a trend toward
improvement observed at the 20-mg dose (p = .0582). Adverse
events were mild to moderate in severity and did not differ in
frequency between beta-methyl-6-chloromelatonin and placebo
significantly decreases both objective and subjective measures of
sleep latency in subjects with primary insomnia. Thus, these data
suggest that melatonin agonists may exert a direct soporific
effect, as previous research indicates that
beta-methyl-6-chloromelatonin is not associated with changes in body
temperature, heart rate, or blood pressure.