Ramelteon for the treatment of insomnia in adults: a systematic review and meta-analysis

Sleep Med. 2014 Apr;15(4):385-92. doi: 10.1016/j.sleep.2013.11.788. Epub 2014 Feb 8.


Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis assessed the efficacy and safety of ramelteon for the treatment of insomnia in adults. We included both published and unpublished data from randomized placebo-controlled trials evaluating the efficacy of ramelteon in adults with insomnia in the analysis. Our primary outcomes were sleep quality, subjective sleep latency (sSL), and subjective total sleep time (sTST). Secondary outcomes included latency to persistent sleep (LPS), total sleep time (TST), sleep efficiency (SE), proportion of rapid eye movement (REM) sleep, wakefulness after sleep onset (WASO), subjective WASO, number of nighttime awakenings (NAW), subjective NAW, and adverse events. Thirteen trials involving 5812 patients with insomnia or insomnia symptoms with a mean study duration of 38 days were pooled. Ramelteon was associated with reduced sSL (weighted mean difference [WMD], -4.30 min [95% confidence interval {CI}, -7.01 to -1.58]) and improved sleep quality (standardized mean differences, -0.074 [95% CI, -0.13 to -0.02]) but was not associated with increased sTST. Ramelteon also was associated with improvement in LPS, SE, and TST. The only significant adverse event was somnolence. Short-term use of ramelteon was associated with improvement in some sleep parameters in patients with insomnia, but its clinical impact is small. Long-term trials are needed before solid conclusions can be established.

Keywords: Insomnia; Melatonin receptor agonist; Meta-analysis; Primary insomnia; Ramelteon; Systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Indenes / adverse effects
  • Indenes / therapeutic use*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Receptors, Melatonin / agonists*
  • Sleep / drug effects
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Treatment Outcome
  • Young Adult


  • Indenes
  • Receptors, Melatonin
  • ramelteon