Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment.
OBJECTIVE
Evaluate the efficacy of ramelteon, an MT/1MT2-receptor agonist, for the treatment of transient insomnia in healthy adults.


METHODS
Randomized, double-blind, placebo-controlled design using a model of transient insomnia related to sleeping in a novel environment.


METHODS
Fourteen sleep research centers.


METHODS
Healthy adults (N=375; 228 women), aged 35 to 60 years, who had never previously slept in a sleep laboratory and had a reported usual sleep duration of 6.5 to 8.5 hours and usual bedtime between 8:30 PM and midnight.


METHODS
Single administration of ramelteon (16 or 64 mg) or placebo 30 minutes before bedtime.


METHODS
Primary efficacy measure was latency to persistent sleep. Also evaluated were total sleep time, wake after sleep onset, percentage of each sleep stage, subjective estimates of sleep from postsleep questionnaire, number of awakenings, and subjective number of awakenings. Residual effects were assessed via Digit Symbol Substitution Test and postsleep questionnaire.


RESULTS
Participants in ramelteon-treated groups had significantly shorter latency to persistent sleep relative to placebo. They also were associated with significantly longer total sleep time. Wake after sleep onset and time spent in each sleep stage were not significantly different from placebo. The use of ramelteon (16 mg) was associated with a shorter subjective sleep latency compared to placebo. Other subjective measures of sleep did not differ significantly from placebo. Digit Symbol Substitution Test scores did not differ significantly among the 3 groups, but the use of the 64-mg [corrected] dose was associated with subjective reports of impairment in the morning.


CONCLUSIONS
Ramelteon significantly improved latency to persistent sleep and total sleep time in this model of transient insomnia in healthy adults. No dose-related differences in latency to persistent sleep were observed, and both doses were well tolerated.
Roth
Thomas
T
Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI 48202, USA. troth1@hfhs.org
Stubbs
Charlene
C
Walsh
James K
JK
D000328:Adult; D004311:Double-Blind Method; D004777:Environment; D005260:Female; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects*; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013997:Time Factors
D007192:Indenes; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; C495910:ramelteon