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In brief: A new sleeping pill

In Brief

A new sleeping pill

The most widely used prescription sleeping pills are benzodiazepines, including lorazepam (Ativan) and the related drugs zolpidem (Ambien) and eszopiclone (Lunesta). Some physicians and patients also favor antidepressants, especially trazodone (Desyrel). Benzodiazepine receptor agonists increase the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is found throughout the brain. Antidepressants influence the neurotransmitters norepinephrine and serotonin, which also have pervasive effects on the brain.

Ramelteon (Rozerem), approved in 2005 by the FDA, is a new kind of sleeping pill, more selective in its effects and — the hope is — safer. Whether it will prove to be as effective is still uncertain. It acts at receptors for the hormone melatonin, which helps to regulate the body's circadian (24-hour) rhythms, including the cycle of sleep and waking.

Ramelteon is a short-acting drug that clears the body within an hour or two. In early trials individuals slept normally, and the drug seemed less likely than benzodiazepine receptor agonists to cause hangovers or rebound insomnia. Animal experiments suggest that, unlike benzodiazepine receptor agonists, it does not cause a withdrawal reaction or create a risk of addiction and abuse. Fatigue, sluggishness, and dizziness are the most common side effects.

Because of insufficient information, ramelteon is not recommended for pregnant women, nursing mothers, or children. Certain drugs, including the antidepressant fluvoxamine (Luvox), compete with ramelteon to bind the enzymes that degrade it, slowing its clearance and increasing the risk of side effects. People with liver disease should not take ramelteon, and combining it with alcohol may cause confusion, irritability, depression, or hallucinations.

To judge ramelteon's risks and benefits more accurately, doctors and patients will have to wait until it has been available longer. It's always important to keep in mind that side effects missed in clinical trials often appear once a drug is in wider use.

Erman M, et al. "An Efficacy, Safety, and Dose-Response Study of Ramelteon in Patients with Chronic Primary Insomnia," Sleep Medicine (January 2006), Vol. 7, No.1, pp. 17–24.

France CP, et al. "Acute and Chronic Effects of Ramelteon in Rhesus Monkeys (Macaca mulatta): Dependence Liability Studies," Behavioral Neuroscience (June 2006), Vol. 120, No. 3, pp. 535–41.

McGechan A, et al. "Ramelteon," CNS Drugs (December 2005), Vol. 19, No. 12, pp. 1057–65.

Roth T, et al. "Effects of Ramelteon on Patient-Reported Sleep Latency in Older Adults with Chronic Insomnia," Sleep Medicine (June 2006), Vol. 7, No. 4, pp. 312–18.

Last updated:	September 05, 2008