Clinical Benefits of Ramelteon for Insomnia Small, Hints New Meta-Analysis
By Reuters Staff
NEW YORK - Short-term use of the selective melatonin receptor agonist ramelteon (Rozerem) is associated with improvement in some sleep parameters in adults with insomnia but its clinical impact is "small," say the authors of an updated meta-analysis of 13 trials.
Ramelteon is currently approved in the United States and Japan for treatment of insomnia.
A prior review and meta-analysis of efficacy studies of ramelteon for chronic insomnia published in 2012 in the International Journal of Clinical Practice suggested that the drug improves both subjective and objective sleep latency and total sleep time.
"However, the number of studies included in the review was small (seven), unpublished data were not included, and a methodologic issue was observed," according to Dr. Akira Kuriyama from Kurashiki Central Hospital in Okayama, Japan, and colleagues.
Their review of ramelteon, online February 10 in Sleep Medicine, included both published and unpublished data from 13 randomized placebo-controlled trials involving 5812 patients treated for 38 days, on average.
Their analysis showed that ramelteon was associated with reduced subjective sleep latency (weighted mean difference, -4.30 minutes; p=0.01) and improved sleep quality (standardized mean difference, -0.074; p=0.74) but not with increased subjective total sleep time (weighted mean difference, 3.23 minutes; p=0.09).
Ramelteon was also associated with increased sleep efficiency (4.42%, p<0.01), increased total sleep time (7.26 minutes, p=0.55), and reduced latency to persistent sleep (-9.36 minutes, p=0.40).
However, the drug was not associated with improvement in other key sleep parameters, including the proportion of REM sleep (-0.08, p=0.88), number of nighttime awakenings (0.50, p=0.82), subjective nighttime awakenings (-0.03, p=0.43), wakefulness after sleep onset (1.95 minutes/night, p=0.76), or subjective wakefulness after sleep onset (3.74 minutes/night, p=0.32).
"Although our study suggested that the improvement of several sleep parameters associated with ramelteon was statistically significant, the magnitude of their improvement was clinically small," the reviewers say.
Ramelteon was "fairly safe; the only statistically significant adverse event was somnolence," they add.
They say their meta-analysis has its share of limitations. The durations of the reviewed studies were relatively short, given that insomnia is a chronic disorder. Meta-regression showed that sleep efficiency with ramelteon "could increase over time. Thus when future trials are conducted with longer durations, results may not support our study," they say.
The fact that many of the trials underreported their methodology is another limitation. Also, the reviewers only had aggregate data. "The lack of patient-level data precluded investigating the statistical heterogeneity for some outcomes," they say.
The authors conclude, "Future clinical trials should examine the efficacy of long-term use of ramelteon on insomnia. They also should report detailed study procedures to facilitate critical appraisals and interpretations. Despite our exhaustive research, no studies have compared ramelteon and other hypnotic agents for insomnia management. To determine the role of ramelteon in the treatment of insomnia, comparative effectiveness studies with ramelteon and other agents should be conducted."
The authors report no conflicts of interest. They did not respond to a request for comment by press time.
