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Eventual Entrainment of the Human Circadian Pacemaker by Melatonin is Independent of the Circadian Phase of Treatment Initiation: Clinical Implications

Sleep and Mood Disorders Laboratory, Departments of Psychiatry, Ophthalmology and Physiology/Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA, lewy{at}ohsu.edu

Jonathan S. Emens

Sleep and Mood Disorders Laboratory, Departments of Psychiatry, Ophthalmology and Physiology/Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA

Rebecca A. Bernert

Sleep and Mood Disorders Laboratory, Departments of Psychiatry, Ophthalmology and Physiology/Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA

Bryan J. Lefler

Sleep and Mood Disorders Laboratory, Departments of Psychiatry, Ophthalmology and Physiology/Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA

About 15% of the legally blind completely lack light perception. Most of these individuals have abnormally phased circadian rhythms and many free-run. Light treatment is not an option for them. However, melatonin treatment can be highly effective. A daily dose of 0.5 mg of melatonin usually results in entrainment. It has been suggested that treatment in individuals with circadian periods > 24 h should be initiated on the advance zone of the melatonin phase response curve, which was based on findings in which melatonin initiated on the delay zone were less likely to result in entrainment, even though treatment continued across all circadian phases. In the present study, 7 totally blind people started low-dose melatonin treatment (0.5 mg; 1 person was given 0.05 mg) on the delay zone. All entrained as circadian phase free-ran and the advance zone of the melatonin phase response curve coincided with the time of melatonin administration. These results are consistent with studies in other mammals. It does not appear that low-dose melatonin treatment needs to be initiated on the advance zone to induce eventual entrainment in blind people with free-running rhythms > 24 h. Therefore, it is not essential that circadian phase be ascertained before starting low-dose melatonin treatment of blind people.

Key Words: circadian • human • melatonin • melatonin phase response curve • entrainment • blindness

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