Is Ramelteon (Romerone) effective for sleep?

Ramelteon (Rozerem) for Sleep Disorders

Ramelteon is moderately effective for treating insomnia characterized by difficulty with sleep onset, but has limited effect on sleep maintenance and overall sleep quality. 1

Efficacy Profile

• Ramelteon is a selective melatonin receptor (MT1 and MT2) agonist that works by enhancing sleep through effects on sleep regulatory mechanisms within the suprachiasmatic nucleus rather than through direct sedation 2
• Ramelteon primarily reduces sleep latency (time to fall asleep) by approximately 9-13 minutes compared to placebo but has minimal effect on total sleep time, sleep efficiency, or sleep quality 3
• The standard therapeutic dose is 8 mg taken 30 minutes before bedtime 3, 1
• Clinical trials supporting its FDA approval showed improvements in objectively measured latency to persistent sleep, but subjective improvements in sleep latency were inconsistent across studies 1, 4
• The American Academy of Sleep Medicine suggests ramelteon as a treatment for sleep onset insomnia with only a WEAK recommendation 3

Safety Profile

• Ramelteon has no abuse liability and is not classified as a controlled substance by the DEA, making it suitable for patients with a history of substance use disorders 2, 5
• The medication is generally well-tolerated with minimal side effects compared to other sleep medications 4, 6
• Somnolence is the main reported adverse effect, occurring in approximately 7% of patients versus 3% with placebo 7
• Unlike benzodiazepines and non-benzodiazepine hypnotics, ramelteon does not cause next-day cognitive or motor impairment, withdrawal symptoms, or rebound insomnia 4, 8
• FDA approval contains no limitation on duration of use, though clinical trials supporting efficacy were up to six months in duration 1

Comparative Efficacy

• For elderly patients, the American Academy of Sleep Medicine recommends suvorexant (15 mg) as the first-line medication for insomnia due to its more favorable efficacy profile (55% response rate vs. 42% with placebo) 9
• Ramelteon showed limited efficacy in clinical trials with older adults, with minimal improvements in sleep onset and no improvement in total sleep time 9
• In a randomized trial investigating ramelteon for prevention of delirium in cardiac surgery patients, it did not show significant benefit (32% vs. 38%, ramelteon vs. placebo) 7

Clinical Application

• Ramelteon is most appropriate for patients specifically struggling with sleep onset rather than sleep maintenance issues 3, 1
• The medication should be taken approximately 30 minutes before bedtime 2
• Patients should be informed that while ramelteon may help them fall asleep faster, the improvement may be modest (approximately 10 minutes) 3, 4
• Ramelteon may be particularly suitable for patients who prefer non-controlled substances or have a history of substance use disorders 3, 2
• First-line treatment for insomnia should still be cognitive behavioral therapy for insomnia (CBT-I) before considering medication 3

Important Considerations

• Ramelteon's effects are primarily on sleep onset; it has little effect on waking after sleep onset (WASO) 3
• The 16 mg dose confers no additional benefit for sleep initiation compared to the 8 mg dose and may increase side effects including fatigue, headache, and next-day somnolence 1
• While ramelteon is FDA-approved without duration limitations, most clinical evidence is from short-term studies, with limited long-term efficacy data beyond 6 months 1, 8