Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain.
Department of Clinical Pharmacology, Organic Chemistry and Paediatrics, Miguel Hernández University of Elche, Elche, Spain.
J Psychopharmacol. 2019 Nov;33(11):1395-1406. doi: 10.1177/0269881119864968. Epub 2019 Aug 19.
Intellectual disability (ID) and autism spectrum disorder (ASD) are common, co-occurring developmental disorders and are frequently associated with sleep problems. This study aimed to assess the effectiveness and tolerability of agomelatine as a pharmacotherapy for sleep problems in ASD adults with ID.
A randomised, crossover, triple-blind, placebo-controlled clinical trial, with two three-month periods of treatment starting with either agomelatine or placebo and a washout period of two weeks. Ambulatory circadian monitoring (24 hours/7 days) evaluated total sleep time (TST) as the primary outcome variable.
Participants (=23; 35±12 years old; 83% male) had a median of three (interquartile range (IQR) 1-4) co-morbidities and were taking a median of five (IQR 2-7) prescribed drugs. Before agomelatine or placebo treatment, all subjects presented with insomnia symptoms, including sleep latency (100% abnormal, 55±23 minutes) or TST (55% abnormal, 449±177 minutes), and 66% had circadian rhythm sleep-wake abnormalities with rhythm phase advancements according to the M5 sleep phase marker values. During the three-month agomelatine treatment, night TST significantly increased by a mean of 83 minutes (16% abnormal, 532±121 minutes), together with a phase correction (M5 1:45±2:28 hours vs. 3:15±2:20 hours), improving sleep stability in wrist temperature rhythm (0.43±0.29 vs. 0.52±0.18 AU). Adverse events were mild and transient.
Agomelatine was effective and well tolerated for treating insomnia and circadian rhythm sleep problems present in adults with ASD and ID.
智力障碍（ID）和自闭症谱系障碍（ASD）是常见的共病性发育障碍，常伴有睡眠问题。本研究旨在评估阿戈美拉汀作为 ASD 合并 ID 成人睡眠问题的药物治疗的有效性和耐受性。
这是一项随机、交叉、三盲、安慰剂对照的临床试验，有两个为期三个月的治疗期，分别从阿戈美拉汀或安慰剂开始，并进行两周的洗脱期。动态昼夜节律监测（24 小时/7 天）评估总睡眠时间（TST）作为主要结局变量。
参与者（n=23；35±12 岁；83%男性）有中位数为 3（四分位距（IQR）1-4）种共病，中位数服用 5（IQR 2-7）种处方药。在阿戈美拉汀或安慰剂治疗前，所有患者均出现失眠症状，包括睡眠潜伏期（100%异常，55±23 分钟）或 TST（55%异常，449±177 分钟），66%存在昼夜节律睡眠-觉醒异常，根据 M5 睡眠相位标志物值出现节律相位提前。在三个月的阿戈美拉汀治疗期间，夜间 TST 平均增加 83 分钟（16%异常，532±121 分钟），同时相位校正（M5 1:45±2:28 小时 vs. 3:15±2:20 小时），改善了腕温节律的睡眠稳定性（0.43±0.29 vs. 0.52±0.18 AU）。不良事件轻微且短暂。
阿戈美拉汀治疗 ASD 合并 ID 成人的失眠和昼夜节律睡眠问题有效且耐受性良好。
