Melatonin is effective in treating sleep problems in Angelman syndrome but problems in metabolising melatonin may be part of the Angelman phenotype
Melatonin is effective in treating sleep problems in Angelman syndrome but problems in metabolising melatonin may be part of the Angelman phenotype
复制标题
褪黑激素可有效治疗天使综合征的睡眠问题，但褪黑激素代谢问题可能是天使表型的一部分
DOI：
10.1111/j.1365-2788.2008.01119_11.x
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发表时间：
2008
影响因子：
3.6
通讯作者：
L. Curfs
中科院分区：
文献类型：
--
作者：
W. Braam;M. Smits;R. Didden;L. Curfs
背景：睡眠问题在Angelman综合征中很常见，而且往往很严重。以前的研究表明，褪黑激素改善了患有安格尔曼综合征的失眠患者的睡眠。方法：我们对8名患有慢性失眠的Angelman综合征儿童进行了随机安慰剂对照研究。患者根据年龄接受褪黑激素5或2.5 mg或安慰剂。父母在日记中记录熄灯时间、睡眠开始、夜间觉醒、醒来时间和癫痫发作。在为期4周的安慰剂对照研究阶段后，所有患者均接受为期4周的褪黑激素开放治疗。我们提供了这8例患者和20例新的AS患者的数据，这些患者在我们的诊所接受治疗，但在本研究中没有描述。结果：在我们的随机研究中，褪黑激素显着提前睡眠开始28分钟，睡眠潜伏期缩短32分钟，总睡眠时间增加56分钟，将醒来的夜晚从每周3.1个晚上减少到1.6个晚上。然而，开放治疗4周后，有些患者的治疗增益有下降的趋势。在基线和第4个治疗周的最后一个晚上（未服用研究药物）测量的唾液内源性褪黑激素水平显示显著增加。在褪黑激素失去作用的AS患者中，褪黑激素水平变得非常高，从而失去了正常的24小时褪黑激素节律。讨论内容：与安慰剂相比，对患有慢性失眠的Angelman综合征儿童进行为期4周的褪黑激素治疗在减少睡眠潜伏期、提前入睡、减少夜间觉醒次数和增加总睡眠时间方面更有效。然而，几周后，褪黑激素在大多数AS患者中失去了有益作用。我们发现AS患者的褪黑激素代谢受到干扰，这可能是AS表型的一部分。
Background: Sleep problems are frequent in Angelman syndrome and often severe. Previous studies suggested that melatonin improves sleep in insomniac patients with Angelman syndrome. Method: We performed a randomized placebo-controlled study in eight children with Angelman syndrome with chronic insomnia. Patients received, depending on age, either melatonin 5 or 2.5 mg, or placebo. Parents recorded lights off time, sleep onset, night wakes, wake-up time and epileptic seizures in a diary. After the 4-week placebo controlled phase of the study, all patients received 4 weeks open treatment with melatonin. We present data on these eight patients and 20 new AS patients that we treated in our clinic and did not describe in this study. Results: In our randomized study melatonin significantly advanced sleep onset by 28 min., decreased sleep latency by 32 min., increased total sleep time by 56 min., reduced the number of nights with wakes from 3.1 to 1.6 nights a week. After 4 weeks of open treatment however, there was in some patients a tendency to a reduction in therapeutic gain. Salivary endogenous melatonin levels, measured at baseline and at the last evening of the fourth treatment week when no study medication was taken, showed a marked increase. In AS patients in whom the melatonin lost its effect, melatonin levels had become extremely high, whereby the normal 24h melatonin rhythm was lost. Discussion: Four weeks of melatonin treatment in Angelman syndrome children with chronic insomnia was more effective in decreasing sleep latency, advancing sleep onset, reducing number of night wakes and increasing total sleep time than placebo. However, after several weeks melatonin lost its beneficial effect in most AS patients. We found indications that melatonin metabolism in AS is disturbed and that this possibly is part of the AS phenotype.