Haas Magali, Karcher Keith, Pandina Gahan J
Johnson & Johnson Pharmaceutical Research and Development, Titusville, New Jersey 08530, USA.
J Child Adolesc Psychopharmacol. 2008 Aug;18(4):337-45. doi: 10.1089/cap.2007.0098.
The aim of this study was to determine the long-term safety of risperidone as maintenance therapy in children and adolescents with disruptive behavior disorders (DBDs) and normal intelligence.
An open-label, 1-year extension study was conducted from January, 2002, to July, 2004, in 232 subjects with DBDs (5-17 years) previously randomized to risperidone (RIS) (n = 115, RIS/RIS) or placebo (PLA) (n = 117, PLA/RIS) in a double-blind, 6-month withdrawal study. Adverse events (AEs) and clinical laboratory test results were recorded. Efficacy was assessed using Nisonger Child Behavior Rating Form. Safety and efficacy were evaluated in the intent-to-treat population.
A total of 169/232 (73%) subjects completed the study. Subjects were predominantly male, with a diagnosis of oppositional defiant disorder. Risperidone was generally well tolerated. Weight gain and extrapyramidal symptoms were each reported as AEs by 10 subjects (4.3%). Mean weight z-scores decreased for RIS/RIS subjects (-0.04 +/- 0.28) and increased for PLA/RIS subjects (0.11 +/- 0.43). No subject developed tardive dyskinesia. Prolactin tended to increase with risperidone, although this effect diminished with prolonged use and was infrequently associated with AEs. There were no clinically relevant changes in glucose or lipid metabolism. Clinical improvement in DBD symptoms was observed with flexible risperidone doses, regardless of previous treatment and whether subjects had experienced symptom recurrence.
Risperidone reinitiated for DBD in children with normal intelligence quotients (IQ) was safe and well tolerated over an additional year of treatment. Patients demonstrated clinical benefits, including those who previously experienced symptom recurrence.
本研究旨在确定利培酮作为维持治疗药物，用于治疗患有破坏性行为障碍（DBD）且智力正常的儿童和青少年的长期安全性。
2002年1月至2004年7月进行了一项开放标签的1年延长期研究，研究对象为232名患有DBD（年龄5 - 17岁）的受试者，这些受试者在之前一项为期6个月的双盲撤药研究中被随机分为利培酮组（RIS）（n = 115，RIS/RIS）或安慰剂组（PLA）（n = 117，PLA/RIS）。记录不良事件（AE）和临床实验室检查结果。使用尼森格儿童行为评定量表评估疗效。在意向性治疗人群中评估安全性和疗效。
共有169/232（73%）名受试者完成了研究。受试者以男性为主，诊断为对立违抗性障碍。利培酮总体耐受性良好。10名受试者（4.3%）报告体重增加和锥体外系症状均为不良事件。RIS/RIS组受试者的平均体重z评分下降（-0.04 ± 0.28），PLA/RIS组受试者的平均体重z评分上升（0.11 ± 0.43）。无受试者发生迟发性运动障碍。催乳素水平倾向于随利培酮治疗而升高，尽管这种效应会随着治疗时间延长而减弱，且很少与不良事件相关。血糖或脂质代谢无临床相关变化。无论先前治疗情况以及受试者是否经历过症状复发，灵活调整利培酮剂量均观察到DBD症状有临床改善。
对于智商正常的儿童，重新启用利培酮治疗DBD，在额外一年的治疗期间是安全且耐受性良好的。患者表现出临床获益，包括那些先前经历过症状复发的患者。
