Can ramelteon (rozerem) be used as needed (prn)?

Ramelteon (Rozerem) Should Not Be Used PRN for Insomnia

Ramelteon is not recommended for as-needed (PRN) use due to its mechanism of action as a melatonin receptor agonist that works best with regular nightly administration. 1

Mechanism of Action and Efficacy Considerations

Ramelteon is a highly selective melatonin MT1/MT2 receptor agonist that primarily targets the body's "master clock" in the suprachiasmatic nucleus, making it a chronohypnotic rather than a traditional sedative hypnotic 2. This distinct mechanism explains why:

• Ramelteon shows only marginal efficacy for sleep onset, with meta-analyses demonstrating a mean reduction in sleep latency of only 9.57 minutes compared to placebo 1
• The drug provides minimal improvement in total sleep time (only about 6.58 minutes) 1
• Its effects on sleep efficiency and sleep quality show no clinically significant improvement over placebo 1

Evidence Against PRN Use

Several factors make ramelteon unsuitable for PRN use:

1. Delayed and Modest Efficacy: The clinical trials showing even modest efficacy for ramelteon were based on nightly use, not intermittent administration 1

2. Plateau Effect: In long-term studies, improvements in sleep parameters reached a plateau by week 20 of continuous use, suggesting the drug works through gradual adjustment of circadian rhythms rather than immediate sedation 3

3. Absence of PRN Studies: No clinical trials have specifically evaluated ramelteon's efficacy when used on an as-needed basis 1

4. Lack of Immediate Sedative Properties: Unlike benzodiazepines or Z-drugs, ramelteon does not directly enhance GABA activity and therefore lacks the immediate sedative effects that would make it suitable for PRN use 2

Safety Profile

While ramelteon has a favorable safety profile compared to other hypnotics, this does not justify PRN use:

• Common adverse effects include somnolence (5% vs 3% for placebo), fatigue (4% vs 2%), and dizziness (5% vs 3%) 4
• Ramelteon lacks abuse potential and dependence risk 4, 5
• No evidence of rebound insomnia or withdrawal symptoms has been observed 6, 3
• The drug does not impair next-day cognitive or motor performance 5

Appropriate Use of Ramelteon

For patients with chronic insomnia characterized by difficulty with sleep onset:

• Ramelteon should be administered at a dose of 8 mg approximately 30 minutes before bedtime on a nightly basis 1
• The drug should be taken consistently at the same time each night to maximize its chronobiotic effects 6
• Patients should be advised that the full benefits may take several weeks of consistent use to become apparent 3
• Treatment duration should be carefully considered, as long-term studies beyond 6 months are limited 6

Clinical Pitfalls to Avoid

1. Expecting Immediate Results: Unlike traditional hypnotics, ramelteon works through regulation of circadian rhythms rather than direct sedation, so patients should not expect immediate sleep induction

2. Inconsistent Timing: Taking ramelteon at variable times can disrupt its chronobiotic effects and reduce efficacy

3. Combining with Other Sedatives: Using ramelteon alongside benzodiazepines or alcohol may increase sedation without improving sleep architecture

4. Unrealistic Expectations: Patients should be informed about the modest effects on sleep latency (approximately 10 minutes improvement) to set appropriate expectations

In conclusion, the available evidence strongly suggests that ramelteon should be used on a scheduled nightly basis rather than as needed (PRN) to achieve even its modest benefits for sleep onset insomnia.