Yanagihara Mariko, Nakamura Masaki, Usui Akira, Nishida Shingo, Ito Eiki, Okawa Masako, Inoue Yuichi
Japan Somnology Center, Neuropsychiatric Research Institute.
Tohoku J Exp Med. 2014 Oct;234(2):123-8. doi: 10.1620/tjem.234.123.
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.
随着生活环境的城市化，昼夜节律睡眠障碍（CRSD）患者的数量一直在增加。CRSD有几种治疗方法可供选择，如光照疗法、药物（褪黑素和维生素B12）以及睡眠卫生教育。然而，尚未确立成功的治疗方法。在自由运行型（FRT）CRSD中，内源性昼夜节律无法与24小时明暗周期同步，导致以比24小时周期长0.5 - 2.5小时的周期自由运行。这种情况在盲人中相对常见，而在有视力的个体中并不常见。在此，我们报告两名有视力的FRT患者，他们用褪黑素受体激动剂雷美替胺成功治疗。患者1（36岁女性）辞职后患有FRT近4个月。起初她接受了睡眠卫生教育并服用雷美替胺，治疗第15天后自由运行周期停止。从第25天起加用三唑仑以促进更早入睡。到第34天时睡眠 - 觉醒时间表恢复正常。患者2（33岁男性）开始休假后患有FRT近8个月。他接受了睡眠卫生教育，并接受雷美替胺和甲钴胺治疗。从首次治疗日起他的睡眠 - 觉醒时间表就恢复了正常。通过雷美替胺的联合治疗，两名患者都维持了良好的睡眠 - 觉醒时间表。雷美替胺对褪黑素2受体的激动作用可能是这些患者自由运行周期停止的主要原因。
