Tohoku J. Exp. Med., 2014 October, 234(2)

The Melatonin Receptor Agonist Is Effective for Free-Running Type Circadian Rhythm Sleep Disorder: Case Report on Two Sighted Patients

MARIKO YANAGIHARA,^1,2,3 MASAKI NAKAMURA,^1,2,4 AKIRA USUI,^1,2,4 SHINGO NISHIDA,^1,2,4 EIKI ITO,^1,2,4 MASAKO OKAWA^1,2,4,5 and YUICHI INOUE^1,2,4

¹Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan
²Yoyogi Sleep Disorder Center, Tokyo, Japan
³First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan
⁴Department of Somnology, Tokyo Medical University, Tokyo, Japan
⁵Japan Foundation for Neuroscience and Mental Health, Kodaira, Tokyo, Japan

Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at first and the free-running cycle stopped after treatment day 15. Triazolam was added from the day 25 to promote earlier sleep onset. And the sleep-wake schedule was normalized by the day 34. Patient 2 (33-year-old male) had suffered from FRT for nearly 8 months after starting to take a leave of absence from his job. He was given sleep hygiene education and was treated with ramelteon and methylcobalamin. His sleep-wake schedule was normalized from the first treatment day. By the combined treatment with ramelteon, both patients have maintained favorable sleep-wake schedules. The agonist action of ramelteon at the melatonin 2 receptor may have primarily contributed to the cessation of the free-running cycle in these patients.

keywords —— circadian rhythm sleep disorder; free running type; melatonin agonist; non-24-hour sleep wake disorder; sighted patient

© 2014 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2014, 234, 123-128

Correspondence: Yuichi Inoue, M.D., Ph.D., Japan Somnology Center, Neuropsychiatric Research Institute, 1-24-10 Yoyogi, Shibuya-ku, Tokyo 151-0053, Japan.

e-mail: inoue@somnology.com