Spencer Thomas J, Greenbaum Michael, Ginsberg Lawrence D, Murphy William Rory
Clinical and Research Program, Pediatric Psychopharmacology, Harvard Medical School and Massachusetts General Hospital , Boston, Massachusetts, USA.
J Child Adolesc Psychopharmacol. 2009 Oct;19(5):501-10. doi: 10.1089/cap.2008.0152.
The aim of this study was to evaluate the safety and effectiveness of guanfacine extended release (GXR) administered concomitantly with psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and suboptimal response to a psychostimulant alone.
This was a multicenter, open-label, 9-week, dose-escalation study of 75 subjects with ADHD treated with methylphenidate (MPH) or amphetamine (AMP) alone for at least 1 month, yet with suboptimal control of ADHD symptoms. Sixty-three subjects (84.0%) completed the study. Patients received GXR in addition to their psychostimulant. Starting with 1 mg/day, GXR was increased weekly to the highest tolerated dose (1, 2, 3, or 4 mg/day), which was maintained through week 6. GXR was then titrated downward in 1-mg weekly decrements from week 7 through week 9. Psychostimulant treatment regimens were continued until at least week 7.
Safety assessments included adverse events (AEs), vital signs, physical examination, clinical laboratory tests, the Pediatric Daytime Sleepiness Scale, and the Pittsburgh Side Effects Rating Scale. Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV), the Conners' Parent Rating Scale-Revised Short Form, Clinical Global Impressions, Parent Global Assessment, and Child Health Questionnaire-Parent Form.
The most common treatment-related AEs were upper abdominal pain (25.3%), fatigue (24.0%), irritability (22.7%), headache (20.0%), and somnolence (18.7%). Most AEs were mild to moderate in severity. Investigator-rated AEs due to blood pressure decreases, heart rate, or electrocardiogram findings were infrequent. Mean changes from baseline (psychostimulant monotherapy just prior to receiving GXR) to end point in ADHD-RS-IV total score were statistically significant overall: -16.1 (p < 0.0001). Significant improvement in both subscales of the ADHD-RS-IV was observed. Improvement of symptoms was observed in a majority of subjects.
Coadministration of GXR and MPH or AMP was generally safe and associated with statistically significant and clinically meaningful ADHD symptom improvement in children and adolescents.
本研究旨在评估在患有注意力缺陷/多动障碍（ADHD）且对单一精神兴奋剂反应欠佳的儿童和青少年中，同时使用缓释胍法辛（GXR）和精神兴奋剂的安全性和有效性。
这是一项多中心、开放标签、为期9周的剂量递增研究，共75名患有ADHD的受试者，他们单独使用哌甲酯（MPH）或苯丙胺（AMP）治疗至少1个月，但ADHD症状控制欠佳。63名受试者（84.0%）完成了研究。患者在服用精神兴奋剂的基础上还接受了GXR治疗。GXR从1毫克/天开始，每周增加至最高耐受剂量（1、2、3或4毫克/天），并维持至第6周。然后从第7周开始至第9周，GXR每周以1毫克的幅度递减。精神兴奋剂治疗方案持续至至少第7周。
安全性评估包括不良事件（AE）、生命体征、体格检查、临床实验室检查、儿科日间嗜睡量表和匹兹堡副作用评定量表。使用ADHD评定量表第四版（ADHD-RS-IV）、康纳斯父母评定量表修订简表、临床总体印象、父母总体评估和儿童健康问卷父母版评估疗效。
最常见的与治疗相关的不良事件为上腹部疼痛（25.3%）、疲劳（24.0%）、易怒（22.7%）、头痛（20.0%）和嗜睡（18.7%）。大多数不良事件的严重程度为轻度至中度。因血压下降、心率或心电图结果导致的研究者评定的不良事件较少见。从基线（接受GXR前的单一精神兴奋剂治疗）到终点，ADHD-RS-IV总分的平均变化总体上具有统计学意义：-16.1（p<0.0001）。ADHD-RS-IV的两个子量表均有显著改善。大多数受试者的症状得到改善。
GXR与MPH或AMP联合使用总体上是安全的，并且与儿童和青少年ADHD症状的统计学显著改善及临床意义上的改善相关。
