From the Guidelines
The maximum recommended dose of ramelteon (Rozerem) is 8 mg taken once daily within 30 minutes before bedtime. This recommendation is based on the most recent and highest quality study available, which suggests that there is no established benefit to exceeding this 8 mg dose, and higher doses have not been shown to provide additional therapeutic effects for insomnia 1. Ramelteon works by selectively targeting melatonin receptors in the brain that help regulate the sleep-wake cycle, specifically the MT1 and MT2 receptors in the suprachiasmatic nucleus.
Key Considerations
- The medication should not be taken with or immediately after a high-fat meal as this can reduce its effectiveness.
- Unlike many other sleep medications, ramelteon is not a controlled substance and does not appear to cause dependence or withdrawal symptoms.
- Patients with severe hepatic impairment should use ramelteon with caution, as their maximum blood levels of the drug may be significantly higher.
- The medication should be avoided in patients taking fluvoxamine, as this can increase ramelteon levels substantially.
Evidence Summary
The evidence from the 2017 clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults supports the use of ramelteon 8 mg for the treatment of sleep onset disturbance, with marginal reduction of sleep latency and minimal increase in total sleep time 1. However, the overall quality of evidence was downgraded to very low due to substantial heterogeneity across studies, imprecision, and potential publication bias. Despite this, the task force determined that the majority of well-informed patients would use ramelteon over no treatment, based on the evidence of improved sleep latency and low potential for adverse events.
Clinical Implications
In clinical practice, the maximum dose of 8 mg should not be exceeded, as higher doses have not been shown to provide additional therapeutic effects for insomnia. Additionally, patients should be cautioned about the potential for adverse effects, such as sleepwalking, eating, driving, and sexual behavior, and advised to use the medication only as prescribed and to avoid combining it with alcohol, other sedatives, or sleep restriction 1.
From the FDA Drug Label
The recommended dose of ramelteon tablets is 8 mg taken within 30 minutes of going to bed. ... The total ramelteon tablets dose should not exceed 8 mg per day. The maximum dose of Ramelteon (Rozerem) is 8 mg per day 2.
- The dose should not exceed 8 mg per day.
From the Research
Maximum Dose of Ramelteon
The maximum dose of Ramelteon (Rozerem) given is not explicitly stated in the provided studies as a universally agreed-upon maximum. However, the doses tested in various studies are as follows:
- Ramelteon is available as an 8 mg tablet, which should be taken approximately 30 minutes prior to bedtime 3.
- Doses of 4,8,16, and 32 mg of Ramelteon were tested in a study, with all doses resulting in statistically significant reductions in latency to persistent sleep (LPS) and increases in total sleep time (TST) 4.
- Another study tested doses of 4,8,16,32, and 64 mg, with no significant next-day residual effects apparent at any dose 5.
- The most common doses used in clinical studies were 4,8, or 16 mg 6.
Key Findings
- Ramelteon has been shown to be effective in decreasing latency to persistent sleep and increasing total sleep time in patients with chronic primary insomnia 4, 6, 7.
- The medication is well-tolerated, with the most commonly reported adverse events being headache, somnolence, and sore throat 4, 7.
- Ramelteon does not have a direct sedating effect, but rather enhances sleep through effects on sleep regulatory mechanisms within the suprachiasmatic nucleus 3.