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Light, melatonin can reset clock in circadian sleep disorders.

SCOTTSDALE, ARIZ.--Before traveling from California to South Africa, Dr. Alon Y. Avidan prepared for the time change by spending afternoons in his office, out of the sun. After he arrived in South Africa, he awoke between 5 a.m. and 7 a.m. every morning and took a walk for an hour or more in bright sunlight.

"In a few days, I was on South African time," he told attendees at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Light therapy can be highly effective in correcting jet lag and other circadian rhythm disorders, according to Dr. Avidan, medical director of the University of California, Los Angeles, neurology clinic and associate director of UCLA's sleep disorders center.

Melatonin, a dietary supplement with no approved medical indications, is another useful treatment when delayed sleep is a problem, he said, and ramelteon (Rozerem) shows promise. Although ramelteon is approved only for insomnia, Dr. Avidan said he prescribes it off label to patients with the type of circadian rhythm disorder that causes night owls to complain they can't fall asleep at normal bedtimes or wake up early in the morning.

Often they are tired all day, but not at night, with detriment to their quality of life. "Circadian-related disruption leads to insomnia, hypersomnia, or both," he said, and it can cause impairment of social, occupational, or other areas of functioning.

Sunlight is the most powerful external time cue for regulating and synchronizing circadian rhythms with the environment, Dr. Avidan said. It promotes wakefulness as input from the retina goes to the suprachiasmatic nucleus (SCN) of the hypothalamus, which contains a circadian pacemaker.

To opposite ends, the pineal gland releases melatonin in response to darkness. Melatonin promotes sleep, but levels of it decrease with aging. Compensating with the dietary supplement has been shown to help advance the circadian clock, according to Dr. Avidan.

For patients with delayed sleep phase, he recommends exposure to bright light--as much as 10,000 amps--in the early morning and taking 0.5 mg of melatonin 5-7 hours before the habitual sleep time, or 12-14 hours before the time a person wishes to awake.

In response to an audience question, Dr. Avidan said several small unpublished studies suggest ramelteon also can advance sleep time. It acts on the melatonin receptors MT1 and MT2, he noted, and is "a true drug." When using ramelteon off label for a circadian sleep disorder, he prescribes a 4-mg dose (which is half the 8-mg dose approved for insomnia).

Advanced sleep-phase disorder is often seen in poorly lit nursing homes, according to Dr. Avidan. People become sleepy very early in the evening, which causes them to go to bed before 8 p.m. and wake, still sleepy, as early as 3 a.m. or 4 a.m. To delay sleep time and wake time, he recommended exposure to bright lights from 7 p.m. to 9 p.m., but not melatonin because--in addition to promoting sleep--it can exacerbate coronary artery disease in some patients.

Irregular sleep-wake patterns also are seen in nursing homes, he noted. In these cases, although residents accumulate normal sleep time for their age, they do so in three or more irregular periods of sleep. Low doses of melatonin did not help in a multicenter study with Alzheimer's disease patients, according to Dr. Avidan, but 10-mg doses produced a trend toward improvement.

"Free-running" sleep disorder with no circadian pattern occurs in about 40% of blind people, Dr. Avidan continued, but is rare in sighted people. He recommended 10 mg of melatonin an hour before bedtime.

For patients whose weariness is related to working night shifts, Dr. Avidan suggested having the patients align circadian rhythms by wearing dark glasses in the morning, keeping the bedroom dark, going to bed soon after the night shift, and seeking exposure to bright light while working. Other possible interventions include stimulants such as caffeine and modafinil (approved for excessive sleepiness caused by shift work), short-acting hypnotics for insomnia, and melatonin to improve duration of daytime sleep, although it has shown little impact on alertness during night shifts.

Finally, the direction of travel can affect the presentation and treatment of jet lag, according to Dr. Avidan. People traveling east across two or more time zones will have difficulty falling asleep, whereas those traveling west may struggle to maintain sleep. In both cases, exposure to and avoidance of light at appropriate times can be "very, very effective." People traveling west should seek morning light at the new location and avoid exposure to light in the evening. When traveling east, they should do the opposite. "Avoid light in the early morning, and get as much light as possible in the afternoon/early evening," Dr. Avidan said.

He advised avoiding excessive use of caffeine and alcohol in either direction, although slow-release caffeine has been shown to improve daytime alertness. Melatonin can foster sleep after an eastbound flight. For specific recommendations geared to time zones of departure and arrival, he recommended using the jet lag calculator in the travel clinic section of www.fleetstreetclinic. com, a British Web site.

Dr. Avidan disclosed receiving a consultant fee and serving on the speakers bureau and adviso ry committee of Takeda Pharma ceutical Co., which sells ramel teon in North America. He also listed relationships with Sepracor Inc., GlaxoSmithKline, and Boehringer Ingelheim.

To avoid jet lag when traveling west, seek morning light at the new location and avoid light in the evening. When traveling east, do the opposite.


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Title Annotation:Psychiatry
Author:Salodof Macneil, Jane
Publication:Internal Medicine News
Geographic Code:1USA
Date:Jul 15, 2008
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