May 2, 2006 Researchers at Oregon Health and Science University (OHSU) have found that melatonin, a naturally occurring brain substance, can relieve the doldrums of winter depression, also known as seasonal affective disorder, or SAD. The study is publishing online this week in the Proceedings of the National Academy of Science.
The study was led by Alfred Lewy, M.D., Ph.D., an internationally recognized pioneer in the study of circadian (24-hour) rhythm disturbances, such as those found in air travelers and shift workers, as well as in totally blind people.
Lewy and his colleagues in the OHSU Sleep and Mood Disorders Lab set out to test the hypothesis that circadian physiological rhythms become misaligned with the sleep/wake cycle during the short days of winter, causing some people to become depressed. Usually these rhythms track to the later dawn in winter, resulting in a circadian phase delay with respect to sleep similar to what happens flying westward. Some people appear to be tracking to the earlier dusk of winter, causing a similar amount of misalignment but in the phase-advance direction. Symptom severity in SAD patients correlated with the misalignment in either direction.
The treatment of choice for most SAD patients is bright light exposure, which causes phase advances when scheduled in the morning. Because patients know when they are exposed to bright light, however, there is a considerable placebo response associated with it. Melatonin can also cause phase advances, but it has to be taken in the afternoon. The Lewy team used afternoon melatonin to test if it was more antidepressant than melatonin taken in the morning, which causes phase delays.
The researchers randomly assigned 68 SAD patients to one of three treatment groups, taking placebo capsules or melatonin in the morning or afternoon for three weeks. After four years of study, they concluded that, similar to persistent jet lag, circadian misalignment is a major part of SAD.
Most patients, typically phase-delayed types or "night owls," have misalignment that responded best to taking low-dose melatonin in the afternoon or evening. A longer-than-expected subgroup of SAD patients, phase-advanced types or "morning larks," responded best to taking low-dose melatonin in the morning. Melatonin did not cause drowsiness, because the doses used were lower than what is usually taken at bedtime.
In addition to bright light exposure, another treatment may be in the offing once low-dose, sustained-release melatonin formulations become available. "However, people in the phase-advanced subgroup should use these treatments at different times of the day than the typically phase-delayed type of patient," explained Lewy, adding that more research is needed.
Lewy is the Richard H. Phillips Professor of Biological Psychiatry, senior vice chairman of psychiatry, and director of the Sleep and Mood Disorders Lab, OHSU School of Medicine.
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