Stein Mark A, Sarampote Christopher S, Waldman Irwin D, Robb Adelaide S, Conlon Charles, Pearl Phillip L, Black David O, Seymour Karen E, Newcorn Jeffrey H
Department of Psychiatry, University of Chicago, Chicago, Illinois 60637, USA.
Pediatrics. 2003 Nov;112(5):e404. doi: 10.1542/peds.112.5.e404.
OROS methylphenidate HCL (MPH) is a recently developed long-acting stimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). This study was conducted to examine dosage effects on ADHD symptoms and stimulant side effects and to explore potential moderating effects of ADHD subtype.
Children with ADHD combined type (ADHD-CT) or predominantly inattentive type (ADHD-PI; n = 47), ages 5 to 16 years, underwent a placebo-controlled, crossover trial using forced titration with weekly switches at 3 dosage levels. Parent and teacher ratings of ADHD symptoms were used to evaluate efficacy. In addition, vital signs and standardized measures of stimulant side effects were obtained weekly.
Parent ratings were more sensitive to treatment effects than teacher ratings. ADHD symptoms and Clinical Global Impressions Severity Index ratings at each dose condition differed significantly from placebo and baseline ratings, which did not differ from one another. For those with ADHD-CT, there was a clear linear dose-response relationship, with clinically significant reductions in ADHD Rating Scale-IV scores occurring in two thirds to three fourths of the subjects during either 36- or 54-mg dose conditions. Children with ADHD-PI, conversely, were more likely to respond optimally to lower doses and derived less benefit from higher doses, with 60% displaying significant improvement on the ADHD Rating Scale-IV at 36 mg or lower. Mild stimulant side effects were reported during placebo and at all dosage levels. With the exception of insomnia and decreased appetite, which were more common at higher doses, parent report of side effects was not related to dose. In addition, younger and smaller children were more likely to display sleep difficulties and decreased appetite at the higher dose levels Although pulse rate increased slightly with increasing dose, there were no dose effects on blood pressure.
In children with ADHD-CT, the most common subtype of ADHD, increasing doses of stimulant medication were associated with increased improvement of inattention and hyperactivity symptoms. In children with ADHD-PI, symptom improvement occurred at lower doses and less benefit was derived from higher doses. In both ADHD subtypes, higher doses were associated with parent ratings of increased insomnia and decreased appetite.
盐酸奥氮平控释片（MPH）是一种最近研发的长效兴奋剂药物，用于治疗注意力缺陷多动障碍（ADHD）。本研究旨在探讨剂量对ADHD症状及兴奋剂副作用的影响，并探究ADHD亚型的潜在调节作用。
年龄在5至16岁的47名患有ADHD混合型（ADHD-CT）或主要为注意力不集中型（ADHD-PI）的儿童，接受了一项安慰剂对照的交叉试验，采用强制滴定法，每周在3个剂量水平进行转换。使用家长和教师对ADHD症状的评分来评估疗效。此外，每周获取生命体征和兴奋剂副作用的标准化测量结果。
家长评分比教师评分对治疗效果更敏感。每个剂量条件下的ADHD症状和临床总体印象严重程度指数评分与安慰剂和基线评分有显著差异，而安慰剂和基线评分之间无差异。对于ADHD-CT患儿，存在明显的线性剂量反应关系，在36毫克或54毫克剂量条件下，三分之二至四分之三的受试者在ADHD评定量表-IV得分上有临床显著降低。相反，ADHD-PI患儿对较低剂量反应更佳，较高剂量获益较少，60%的患儿在36毫克或更低剂量时ADHD评定量表-IV显示有显著改善。在安慰剂和所有剂量水平下均报告有轻度兴奋剂副作用。除了失眠和食欲减退在较高剂量时更常见外，家长报告的副作用与剂量无关。此外，年龄较小和体型较小的儿童在较高剂量水平时更易出现睡眠困难和食欲减退。尽管脉搏率随剂量增加略有上升，但血压无剂量效应。
在ADHD最常见的亚型ADHD-CT患儿中，兴奋剂药物剂量增加与注意力不集中和多动症状改善增加相关。在ADHD-PI患儿中，较低剂量时症状改善，较高剂量获益较少。在两种ADHD亚型中，较高剂量与家长报告的失眠增加和食欲减退相关。
