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 2016 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
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.