FDA Approves New Kind of Sleeping Pill

Rozerem First Drug to Target Brain's Sleep Center

From the WebMD Archives

July 22, 2005 -- Rozerem, the first of a new kind of sleeping pill, has been approved by the FDA.

Before this approval, many sleeping pills had potential narcotic-like effects. True, new nonbenzodiazepine sleeping pills -- such as Ambien, Lunesta, and Sonata -- have greatly reduced abuse potential. But they still have a sedating effect throughout the brain. And like earlier sleep drugs, they are controlled substances under federal law.

Rozerem (8-milligram tablets) is the first and only noncontrolled prescription medication for use of insomnia in adults. It is prescribed for insomnia characterized by difficulty with sleep onset.

Rozerem can be prescribed for long-term use. The medication has shown no evidence of abuse and dependence, according to a news release by Takeda Pharmaceuticals North America, the drug's maker.

Rozerem is different from other sleep drugs. It targets specific switches in the part of the brain that regulate sleep, a group of brain cells located in an area of the brain called the SCN. By flipping these switches -- called melatonin receptors -- Rozerem takes the brakes off the body's natural sleep drive.

Body Boot-Down

Here's how it's thought to work. The body has a sleep drive as well as a waking drive. As the day wears on, the sleep drive builds up. But it doesn't make you fall asleep in the daytime, because that's when the waking drive is stronger. Later in the evening, the waking drive winds down while the sleep drive continues to build up. By bedtime, the sleep drive is stronger -- and you're ready for normal sleep.

If you've got insomnia, the sleep and waking drives get out of balance. Most sleeping pills work by enhancing the sleep drive. Rozerem seems to work by relaxing the waking drive, says psychiatrist Louis J. Mini, MD, Takeda North America's medical director for neuroscience.

"In people who sleep normally, the pineal gland in the brain responds to darkness by producing a hormone called melatonin," Mini says. "This natural melatonin ... dampens the alerting signal so the sleep load overrides [the waking drive] and allows a person to fall asleep."

Unlike melatonin, which has widespread effects throughout the body, Rozerem sends two specific melatonin-like signals to the brain's sleep center. This reduces the alerting signal at the time a person wants to go to sleep.

"It is like shutting down a computer," Mini says. "You can pull the plug and it goes off -- that's how we see traditional sleep drugs -- but when you restart the computer, it takes a while. Or you can sign off appropriately, and let the computer boot down. We see Rozerem as letting the body boot down in normal fashion."

All that is still theoretical -- but it makes sense to David Neubauer, MD, associate director of the Johns Hopkins Sleep Disorders Center and author of Understanding Sleeplessness: Perspectives on Insomnia.

"It is clear that something critical is happening at the end of waking time so the body lets us transition rather rapidly from being awake to being asleep," Neubauer tells WebMD. "A lot of this has to do with the SCN. And as [Rozerem] targets melatonin receptors in the SCN, it makes sense it can make a gearshift toward sleep."

What Sleep Doctors Say

Is Rozerem going to affect the way doctors treat patients?

"I am delighted to have another thing to offer to my patients," Neubauer says. "There will be a lot of interest. One -- because it is the first sleep drug in a very long time to have a new mechanism of action. And two -- I think there is going to be a very high comfort level in prescribing this drug. The safety level is extremely positive. A lot of doctors -- and a lot of patients who haven't been interested in a sleeping pill -- may view this in a different light and may be more comfortable giving it a try."

But Milton Kramer, MD, isn't sure Rozerem is going to be better than existing sleeping pills. Kramer is director of psychiatric research, Maimonides Medical Center, Brooklyn, N.Y.

"I don't think [Rozerem] is going to have an enormous impact," Kramer tells WebMD. "The issue is around the size of the change it accomplishes -- its effectiveness in chronic [sleeping-pill] users is not enormous. But people may see it as being a more 'natural' substance, and that may give it tremendous appeal."

Rozerem should be taken within 30 minutes before going to bed. It should not be taken with or immediately after a high-fat meal. Engaging in hazardous activities that require concentration (such as operating a motor vehicle or heavy machinery) after taking Rozerem should be avoided.

The most common side effects seen with Rozerem were somnolence, dizziness, and fatigue. Rozerem should not be used in people with severe liver abnormalities.

Rozerem vs. Melatonin

So wouldn't over-the-counter melatonin supplements work as well as Rozerem? No, Mini says. Rozerem has a more potent effect on the sleep center of the brain than melatonin supplements. And unlike the supplement, Rozerem has been tested in well-designed studies.

"If you look at the melatonin data, and the recent NIH consensus panel statement, it says that there is little evidence to support the use of melatonin for the treatment of insomnia," Mini says. "And even at that, the dose needed for sleep promotion is unclear. Strict clinical trials of melatonin have not been done. It is an unregulated supplement."

According to the Takeda news release, Rozerem will be available for patients by late August.

Show Sources

SOURCES: Physician's Desk Reference, 2005. Louis J. Mini, MD, medical director, neuroscience, Takeda North America. David Neubauer, MD, associate director, Johns Hopkins Sleep Disorders Center; author, Understanding Sleeplessness: Perspectives on Insomnia, Johns Hopkins University Press, 2003. Takeda web site, News releases, Takeda Pharmaceuticals. Milton Kramer, MD, director, Sleep Disorders Center, Bethesda Hospital, Cincinnati; volunteer professor of psychiatry and adjunct professor, University of Cincinnati; clinical professor of psychiatry, Wright State University School of Medicine, Dayton, Ohio.

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