Pandina Gahan J, Zhu Young, Cornblatt Barbara
Johnson & Johnson Pharmaceutical Research & Development, Titusville, New Jersey 08560, USA.
J Child Adolesc Psychopharmacol. 2009 Dec;19(6):749-56. doi: 10.1089/cap.2008.0159.
The aim of this study was to evaluate cognitive effects from long-term risperidone treatment for disruptive behavior disorders (DBDs) in children and adolescents.
Patients 5-17 years old with DBDs and an intelligence quotient (IQ) > or =54 were randomized to flexibly dosed risperidone or placebo in a 6-month recurrence prevention trial. Cognitive function was assessed with a modified California Verbal Learning Test for Children (MVLT-C) and Continuous Performance Test (CPT), which assessed vigilance through computer testing with both an easy and a hard test. Somnolence was also evaluated throughout treatment. Clinically meaningful treatment effects were assessed as changes of > or =0.5 or > or =1.0 standard deviation (SD) from baseline.
A total of 284 subjects participating in 6-month maintenance treatment had both baseline and end point cognition assessments and were included in this analysis. Significant improvements from baseline occurred in risperidone-treated subjects for CPT hard hit rates and discrimination ability (Pr) (p < 0.05 for both), and in placebo subjects for CPT easy false alarms rates (p < 0.001) and hard Pr (p < 0.05). Both the easy and hard CPTs correct mean response time worsened with placebo. The MVLT-C short-delay free recall improved significantly for both risperidone and placebo. After adjusting for country, somnolence, age, IQ, and baseline scores, no significant differences were noted in cognition between treatment groups. Clinically meaningful changes were generally similar for risperidone and placebo patients. Mild to moderate somnolence occurred in only 2% of patients treated with either risperidone or placebo. The change in cognitive testing was not different in subjects experiencing somnolence as an adverse event (AE) compared with subjects not experiencing somnolence.
Risperidone treatment resulted in no decline in cognitive function among children and adolescents. These results extend on previous results from risperidone studies in DBD in patients with lower IQ.
本研究旨在评估长期使用利培酮治疗儿童和青少年破坏性行为障碍（DBD）的认知影响。
在一项为期6个月的预防复发试验中，将年龄在5至17岁、患有DBD且智商（IQ）≥54的患者随机分为灵活给药的利培酮组或安慰剂组。使用改良的儿童加利福尼亚言语学习测试（MVLT-C）和连续性能测试（CPT）评估认知功能，CPT通过简单和困难测试的计算机测试评估警觉性。在整个治疗过程中还评估了嗜睡情况。将具有临床意义的治疗效果评估为相对于基线变化≥0.5或≥1.0标准差（SD）。
共有284名参与6个月维持治疗的受试者进行了基线和终点认知评估，并纳入本分析。利培酮治疗组受试者的CPT困难击中率和辨别能力（Pr）较基线有显著改善（两者p<0.05），安慰剂组受试者的CPT简单误报率（p<0.001）和困难Pr（p<0.05）较基线有显著改善。安慰剂组的CPT简单和困难测试的正确平均反应时间均变差。利培酮组和安慰剂组的MVLT-C短延迟自由回忆均有显著改善。在调整国家、嗜睡情况、年龄、智商和基线分数后，治疗组之间在认知方面未发现显著差异。利培酮组和安慰剂组患者具有临床意义的变化总体相似。使用利培酮或安慰剂治疗的患者中，只有2%出现轻度至中度嗜睡。作为不良事件（AE）经历嗜睡的受试者与未经历嗜睡的受试者相比，认知测试的变化没有差异。
利培酮治疗不会导致儿童和青少年认知功能下降。这些结果扩展了之前对低智商DBD患者进行的利培酮研究结果。
