van der Heijden Kristiaan B, Smits Marcel G, van Someren Eus J W, Boudewijn Gunning W
Department of Child and Adolescent Psychiatry, University of Amsterdam, Amsterdam, The Netherlands.
J Sleep Res. 2005 Jun;14(2):187-94. doi: 10.1111/j.1365-2869.2005.00451.x.
Research has shown efficacy of melatonin treatment to advance sleep-wake rhythms in insomnia. In healthy adults, direction and magnitude of the phase shift depends on the timing of administration relative to the phase position of the circadian system. Therefore, in the present study we investigated whether in children with chronic sleep onset insomnia (SOI) efficacy of melatonin treatment in the early evening could be predicted from dim light melatonin onset (DLMO), a phase marker of the circadian system. We combined data of two previously published double blind, randomized, placebo-controlled trials in 110 participants, aged 6-12 years. Sleep was actigraphically estimated, and saliva collected, at baseline and in the third week of a 4-week treatment period with 5 mg melatonin or placebo at 18:00 or 19:00 hours. Primary outcome measures were pre- to post-treatment changes in dim light melatonin onset (DeltaDLMO), sleep onset (DeltaSO), sleep latency (DeltaSL), and total sleep duration (DeltaTSD). Melatonin advanced DLMO with +1:12 h (P < 0.001), SO with +0:42 h (P = 0.004), SL decreased with 25 min (P = 0.019), and TSD did not change significantly, as compared with placebo. In the melatonin-treated group, but not in the placebo-treated group, pretreatment DLMO was significantly related to DeltaDLMO [F(1, 29) = 7.28, P = 0.012] and DeltaSO [F(1, 25) = 7.72, P = 0.010]. The time interval between treatment administration and pretreatment DLMO (INT) was only significantly related to DeltaSO [F(1,26) = 5.40, P = 0.028]. The results suggest that in children with SOI, the efficacy of early evening melatonin to advance sleep onset and endogenous melatonin onset increases the later the pretreatment DLMO is.
研究表明褪黑素治疗可改善失眠患者的睡眠-觉醒节律。在健康成年人中,相位偏移的方向和幅度取决于给药时间相对于昼夜节律系统相位位置的关系。因此,在本研究中,我们调查了对于患有慢性入睡困难型失眠(SOI)的儿童,能否根据昼夜节律系统的相位标记——暗光褪黑素起始时间(DLMO)来预测傍晚早期褪黑素治疗的疗效。我们合并了之前发表的两项双盲、随机、安慰剂对照试验的数据,这两项试验共有110名6至12岁的参与者。在基线以及为期4周的治疗期的第三周,通过活动记录仪估计睡眠情况,并采集唾液样本,治疗采用5毫克褪黑素或安慰剂,给药时间为18:00或19:00。主要结局指标为治疗前至治疗后暗光褪黑素起始时间的变化(DeltaDLMO)、入睡时间(DeltaSO)、睡眠潜伏期(DeltaSL)和总睡眠时间(DeltaTSD)。与安慰剂相比,褪黑素使DLMO提前了+1:12小时(P < 0.001),SO提前了+0:42小时(P = 0.004),SL缩短了25分钟(P = 0.019),TSD无显著变化。在褪黑素治疗组中,而非安慰剂治疗组中,治疗前的DLMO与DeltaDLMO [F(1, 29) = 7.28, P = 0.012] 和DeltaSO [F(1, 25) = 7.72, P = 0.010] 显著相关。治疗给药与治疗前DLMO之间的时间间隔(INT)仅与DeltaSO显著相关 [F(1,26) = 5.40, P = 0.028]。结果表明,对于患有SOI的儿童,傍晚早期褪黑素促进入睡和内源性褪黑素起始的疗效会随着治疗前DLMO的延迟而增加。