Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia.
OBJECTIVE
Long-duration (> or = 6 months) polysomnographic studies of insomnia medications are lacking. This study evaluated the long-term efficacy of ramelteon, a selective MT1/MT2 melatonin-receptor agonist used for insomnia treatment.


METHODS
Six-month, randomized, double-blind, placebo-controlled study.


METHODS
Forty-six investigative sites in the United States, Europe, Russia, and Australia.


METHODS
Four hundred fifty-one adults (age > or = 18 years) with chronic primary insomnia.


METHODS
Ramelteon, 8 mg, or placebo 30 minutes before bedtime nightly for 6 months.


METHODS
Sleep was evaluated by polysomnography and morning questionnaires on the first 2 nights of Week 1; the last 2 nights of Months 1, 3, 5, and 6; and Nights 1 and 2 of the placebo run-out. Next-morning residual effects as well as adverse effects and vital signs were recorded at each visit. Rebound insomnia and withdrawal effects were evaluated during placebo run-out.


RESULTS
Over the 6 months of treatment, ramelteon consistently reduced latency to persistent sleep compared with baseline and with placebo; significant decreases were observed at Week 1 and Months 1, 3, 5, and 6 (P < 0.05). Ramelteon significantly reduced subjective sleep latency relative to placebo at Week 1, Month 1, and Month 5 (P < 0.05), with reductions nearing statistical significance at Months 3 and 6 (P < or = 0.08). No significant next-morning residual effects were detected during ramelteon treatment. No withdrawal symptoms or rebound insomnia were detected after ramelteon discontinuation. Most adverse events were mild or moderate in severity.


CONCLUSIONS
In adults with chronic insomnia, long-term ramelteon treatment consistently reduced sleep onset, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.
Mayer
Geert
G
Hephata-Klinik, Schwalmstadt, Germany. geert.mayer@hephata.com
Wang-Weigand
Sherry
S
Roth-Schechter
Barbara
B
Lehmann
Reiner
R
Staner
Corinne
C
Partinen
Markku
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001288:Attention / Q000187:drug effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D007192:Indenes / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D017286:Polysomnography / Q000187:drug effects; D011446:Prospective Studies; D012153:Retention, Psychology / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects; D055815:Young Adult
D006993:Hypnotics and Sedatives; D007192:Indenes; C495910:ramelteon