Department of Research and Development, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA.
J Clin Psychiatry. 2011 Sep;72(9):1270-6. doi: 10.4088/JCP.09m05933. Epub 2011 Jul 26.
Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects (6-17 years) with autistic disorder.
A 52-week, open-label, flexibly dosed (2-15 mg/d) study of the safety and tolerability of aripiprazole in outpatients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent, 8-week randomized trials or were enrolled de novo (ie, not treated in the randomized trials). Safety and tolerability measures included incidences of adverse events, extrapyramidal symptoms, weight, metabolic measures, vital signs, and other clinical assessments.
Subjects were enrolled between September 2006 and June 2009. Three hundred thirty subjects entered the treatment phase: 86 de novo, 174 prior aripiprazole, and 70 prior placebo. A total of 199 (60.3%) subjects completed 52 weeks of treatment. Adverse events were experienced by 286/330 subjects (86.7%). Common adverse events included weight increase, vomiting, nasopharyngitis, increased appetite, pyrexia, upper respiratory tract infection, and insomnia. Discontinuations due to adverse events occurred in 35/330 randomized subjects (10.6%)-most commonly aggression and weight increase. One patient discontinued from the study due to a laboratory-related adverse event (moderately increased alanine transaminase and aspartate transaminase). Nine subjects experienced serious adverse events-most frequently aggression. Extrapyramidal symptoms-related adverse events occurred in 48/330 subjects (14.5%)-most commonly tremor (3.0%), psychomotor hyperactivity (2.7%), akathisia (2.4%), and dyskinesia (not tardive, 2.4%). At > 9 months' aripiprazole exposure (n = 220), mean change in body weight z score was 0.33 and body mass index z score was 0.31. The percentages of subjects with clinically significant fasting metabolic abnormalities at > 9 months were 2% for glucose, 5% for total cholesterol, 7% for low-density lipoprotein cholesterol, 30% for high-density lipoprotein cholesterol, and 5% for triglycerides.
Aripiprazole was generally safe and well tolerated in the long-term treatment of irritability associated with autistic disorder in pediatric subjects. Weight should be proactively monitored during long-term treatment.
clinical trials.gov Identifier: NCT00365859.
评估阿立哌唑治疗儿童自闭症（6-17 岁）烦躁症的长期安全性和耐受性。
这是一项为期 52 周、开放性、剂量灵活（2-15mg/d）的研究，评估了阿立哌唑治疗符合 DSM-IV-TR 自闭症诊断标准的门诊患者的安全性和耐受性，这些患者之前完成了 2 项为期 8 周的随机试验中的 1 项，或者是新入组的患者（即未在随机试验中治疗过）。安全性和耐受性评估包括不良事件、锥体外系症状、体重、代谢指标、生命体征和其他临床评估的发生率。
受试者于 2006 年 9 月至 2009 年 6 月入组。330 名受试者进入治疗阶段：86 名新入组，174 名曾接受阿立哌唑治疗，70 名曾接受安慰剂治疗。共有 199 名（60.3%）受试者完成了 52 周的治疗。330 名随机受试者中有 286 名（86.7%）出现了不良事件。常见的不良事件包括体重增加、呕吐、鼻咽炎、食欲增加、发热、上呼吸道感染和失眠。35 名（10.6%）随机受试者因不良事件停药，最常见的是攻击行为和体重增加。1 名患者因实验室相关不良事件（丙氨酸氨基转移酶和天门冬氨酸氨基转移酶中度升高）退出研究。9 名受试者出现严重不良事件，最常见的是攻击行为。锥体外系症状相关不良事件发生在 48 名（14.5%）受试者中，最常见的是震颤（3.0%）、精神运动过度活跃（2.7%）、静坐不能（2.4%）和运动障碍（非迟发性，2.4%）。在 >9 个月的阿立哌唑暴露（n=220）中，体重 z 评分的平均变化为 0.33，体重指数 z 评分的平均变化为 0.31。在 >9 个月时，葡萄糖、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯的临床显著空腹代谢异常的受试者百分比分别为 2%、5%、7%、30%和 5%。
在长期治疗儿童自闭症相关烦躁症时，阿立哌唑总体上是安全且耐受良好的。在长期治疗期间，应积极监测体重。
临床试验.gov 标识符：NCT00365859。
