Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.
Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.
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DOI：
10.1089/cap.2015.0146
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发表时间：
2017-06
影响因子：
1.9
通讯作者：
Katz E
中科院分区：
文献类型：
--
作者：
Aman MG;Findling RL;Hardan AY;Hendren RL;Melmed RD;Kehinde-Nelson O;Hsu HA;Trugman JM;Palmer RH;Graham SM;Gage AT;Perhach JL;Katz E
目的：异常的多巴胺能神经传递参与了自闭症谱系障碍（ASD）的病理生理过程。在这项研究中，在一项随机、安慰剂对照、为期12周的试验和为期48周的开放标签扩展研究中，研究了多巴胺能N-甲基-d-天冬氨酸（NMDA）受体拮抗剂美金刚（每日一次缓释[ER]）在自闭症儿童中的安全性、耐受性和疗效。方法：采用《精神障碍诊断与统计手册》第4版，文本修订版（DSM-IV-TR）定义的自闭症患者随机（1：1）接受安慰剂或美金刚ER治疗12周; 104名儿童进入随后的扩展试验。最大美金刚剂量由体重决定，范围为3 - 15 mg/天。结果如下：在12周研究中发生了1起严重不良事件（SAE）（情感障碍，美金刚），在48周扩展期发生了1起SAE（大叶性肺炎）;均被认为与治疗无关。其他AE被认为是轻度或中度，大多数被认为与治疗无关。临床实验室检查值、生命体征或心电图（ECG）未发生具有临床意义的变化。在社会反应量表（SRS）的护理人员/父母评级的主要疗效结局方面，组间无显著差异，尽管在两组中均观察到第12周时较基线改善。在48周延长期结束时观察到改善趋势。活性药物组在任何次要终点上均未观察到改善，12周后，与安慰剂相比，美金刚的一项沟通测量显示显著恶化（p = 0.02）。结论：这项试验没有证明美金刚ER治疗自闭症的临床疗效;然而，耐受性和安全性数据令人放心。我们的研究结果可以为将来在这一人群中的试验设计提供信息，并有助于美金刚ER在其他临床应用中的研究。
Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. Methods: A total of 121 children 6–12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. Results: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. Conclusions: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.
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影响因子：
3.6
作者：
Horsman J;Furlong W;Feeny D;Torrance G
通讯作者：
Torrance G
影响因子：
26.1
作者：
King BH;Dukes K;Donnelly CL;Sikich L;McCracken JT;Scahill L;Hollander E;Bregman JD;Anagnostou E;Robinson F;Sullivan L;Hirtz D
通讯作者：
Hirtz D
影响因子：
1.9
作者：
Findling, Robert L.;McNamara, Nora K.;Graham, Stephen M.
通讯作者：
Graham, Stephen M.
影响因子：
3.6
作者：
LOYD, BH;ABIDIN, RR
通讯作者：
ABIDIN, RR
影响因子：
3.7
作者：
Curran, Monique P.
通讯作者：
Curran, Monique P.