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An efficacy, safety, and dose–response study of Ramelteon in patients
with chronic primary insomnia
Milton Ermana, Corresponding Author Contact Information, E-mail
The Corresponding Author, David Seidenb, Gary Zammitc, Stephen Sainatid
and Jeffrey Zhangd
Received 6 July 2004; revised 13 September 2005; accepted 20 September
2005. Available online 23 November 2005.
Background and purpose
To evaluate the efficacy, safety, and dose response of Ramelteon,
a novel highly selective MT1/MT2 receptor agonist, in patients with
chronic primary insomnia.
Patients and methods
A randomized, multicenter, double-blind, placebo-controlled, five-period
crossover study design was performed. A total of 107 patients, aged
18–64 years, were randomized into a dosing sequence that included
4, 8, 16, and 32 mg of ramelteon and placebo. Patients received all
five treatments, with a 5- to 12-day washout period between treatments,
and served as their own controls. Medication was administered 30 min
before habitual bedtime and polysomnographic monitoring. Next-day
residual effects were assessed with two visual analog scales (mood
and feeling), digit symbol substitution test (DSST), word-list memory
tests (immediate recall and delayed recall), and a post-sleep questionnaire
that ascertained patients' alertness and ability to concentrate.
Results
All tested doses of ramelteon resulted in statistically significant
reductions in latency to persistent sleep (LPS) and increases in total
sleep time (TST). No next-day residual effects were apparent at any
dose, as compared with placebo. There were no differences in the number
or type of adverse events between any active treatment and placebo
group. The most commonly reported adverse events were headache, somnolence,
and sore throat.
Conclusions
Ramelteon demonstrated a statistically significant reduction in LPS
and a statistically significant increase in TST, with no apparent
next-day residual effects, in patients with chronic primary insomnia.
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