Maras Athanasios, Schroder Carmen M, Malow Beth A, Findling Robert L, Breddy John, Nir Tali, Shahmoon Shiri, Zisapel Nava, Gringras Paul
Yulius Academy, Yulius Mental Health Organization, Barendrecht, The Netherlands.
Strasbourg University Hospital Department of Child and Adolescent Psychiatry, Strasbourg, France.
J Child Adolesc Psychopharmacol. 2018 Dec;28(10):699-710. doi: 10.1089/cap.2018.0020. Epub 2018 Oct 11.
A recent double-blind randomized placebo-controlled study demonstrated 3-month efficacy and safety of a novel pediatric-appropriate prolonged-release melatonin (PedPRM) for insomnia in children and adolescents with autism spectrum disorder (ASD) and neurogenetic disorders (NGD) with/without attention-deficit/hyperactivity disorder comorbidity. Long-term efficacy and safety of PedPRM treatment was studied. A prospective, open-label efficacy and safety follow-up of nightly 2, 5, or 10 mg PedPRM in subjects who completed the 13-week double-blind trial (51 PedPRM; 44 placebo). Measures included caregiver-reported Sleep and Nap Diary, Composite Sleep Disturbance Index (CSDI), caregiver's Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and quality of life (WHO-5 Well-Being Index). Ninety-five subjects (74.7% males; mean [standard deviation] age, 9 [4.24]; range, 2-17.5 years) received PedPRM (2/5 mg) according to the double-blind phase dose, for 39 weeks with optional dose adjustment (2, 5, or 10 mg/day) after the first 13 weeks. After 52 weeks of continuous treatment (PedPRM-randomized group) subjects slept (mean [SE]) 62.08 (21.5) minutes longer ( = 0.007); fell asleep 48.6 (10.2) minutes faster ( < 0.001); had 89.1 (25.5) minutes longer uninterrupted sleep episodes ( = 0.001); 0.41 (0.12) less nightly awakenings (>50% decrease; = 0.001); and better sleep quality ( < 0.001) compared with baseline. The placebo-randomized group also improved with PedPRM. Altogether, by the end of 39-week follow-up, regardless of randomization assignment, 55/72 (76%) of completers achieved overall improvement of ≥1 hour in total sleep time (TST), sleep latency or both, over baseline, with no evidence of decreased efficacy. In parallel, CSDI child sleep disturbance and caregivers' satisfaction of their child's sleep patterns ( < 0.001 for both), PSQI global ( < 0.001), and WHO-5 ( = 0.001) improved in statistically significant and clinically relevant manner ( = 72) compared with baseline. PedPRM was generally safe; most frequent treatment-related adverse events were fatigue (5.3%) and mood swings (3.2% of patients). PedPRM, an easily swallowed formulation shown to be efficacious versus placebo, is an efficacious and safe option for long-term treatment (up to 52 weeks reported here) of children with ASD and NGD who suffer from insomnia and subsequently improves caregivers' quality of life.
最近一项双盲随机安慰剂对照研究证明了一种新型儿科专用长效褪黑素（PedPRM）对患有或不患有注意力缺陷多动障碍合并症的自闭症谱系障碍（ASD）和神经遗传性疾病（NGD）的儿童及青少年失眠症的3个月疗效和安全性。研究了PedPRM治疗的长期疗效和安全性。对完成13周双盲试验的受试者（51例PedPRM组；44例安慰剂组）进行前瞻性、开放标签的疗效和安全性随访，受试者每晚服用2、5或10毫克PedPRM。测量指标包括照料者报告的睡眠和小睡日记、综合睡眠障碍指数（CSDI）、照料者的匹兹堡睡眠质量指数（PSQI）、爱泼华嗜睡量表和生活质量（WHO-5幸福指数）。95名受试者（74.7%为男性；平均[标准差]年龄9[4.24]岁；范围2-17.5岁）按照双盲阶段剂量接受PedPRM（2/5毫克）治疗，持续39周，在前13周后可进行剂量调整（2、5或10毫克/天）。连续治疗52周后（PedPRM随机分组组），受试者的睡眠时间（平均[标准误]）比基线时长62.08（21.5）分钟（P=0.007）；入睡速度快48.6（10.2）分钟（P<0.001）；不间断睡眠时长延长89.1（25.5）分钟（P=0.001）；夜间觉醒次数减少0.41（0.12）次（减少>50%；P=0.001）；睡眠质量更好（P<0.001）。安慰剂随机分组组接受PedPRM治疗后也有改善。总体而言，在39周随访结束时，无论随机分组情况如何，72名完成者中有55名（76%）的总睡眠时间（TST）、睡眠潜伏期或两者相比基线总体改善≥1小时，且没有疗效降低的证据。同时，与基线相比，CSDI儿童睡眠障碍和照料者对其孩子睡眠模式的满意度（两者P<0.001）、PSQI总体评分（P<0.001）和WHO-5评分（P=0.001）均有统计学意义且具有临床相关性的改善（n=72）。PedPRM总体安全；最常见的与治疗相关的不良事件是疲劳（5.3%）和情绪波动（3.2%的患者）。PedPRM是一种易于吞咽的制剂，与安慰剂相比显示有效，是对患有失眠症的ASD和NGD儿童进行长期治疗（本文报道长达52周）的有效且安全的选择，随后可改善照料者的生活质量。
