Pelham W E, Aronoff H R, Midlam J K, Shapiro C J, Gnagy E M, Chronis A M, Onyango A N, Forehand G, Nguyen A, Waxmonsky J
Department of Psychology, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Pediatrics. 1999 Apr;103(4):e43. doi: 10.1542/peds.103.4.e43.
Very little research has focused on the efficacy of Adderall (Shire-Richwood Inc, Florence, KY) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD), and no studies have compared it with standardized doses of Ritalin (Novartis Pharmaceuticals, East Hanover, NJ). It is thought that Adderall has a longer half-life than Ritalin and might minimize the loss of efficacy that occurs 4 or 5 hours after Ritalin ingestion. We compared two doses of Ritalin and Adderall in the treatment of ADHD in children in an acute study and assessed the medications' time courses.
Within-subject, double-blind, placebo-controlled, crossover design lasting 6 weeks. As in our previous work, medication changes occurred on a daily basis in random order over days.
Eight-week, weekday (9 hours daily) summer treatment program at the State University of New York at Buffalo, using an intensive behavioral treatment program including a point system and parent training.
Twenty-five children (21 boys and 4 girls) diagnosed as ADHD using standardized structured interview and rating scales, mean age 9.6 years, 88% Caucasian, of average intelligence, with no medical conditions that would preclude a trial of stimulant medication. Thirteen were comorbid for oppositional-defiant disorder and another 8 for conduct disorder.
Children received 10 mg of Ritalin, 17.5 mg of Ritalin, 7.5 mg of Adderall, 12.5 mg of Adderall, or placebo, twice a day (7:45 AM and 12:15 PM), in random order with conditions changing daily for 24 days.
Daily rates of behaviors in recreational and classroom settings, and standardized ratings from counselors, teachers, and parents, were averaged across days within condition within child and compared. Within-subject relative sizes of the medication effects were computed by taking the placebo-minus-drug mean difference divided by the placebo standard deviation for each child, and were compared hourly between first daily ingestion (7:45 AM) and 5:00 PM to assess the time course of the two drugs. Measures were taken at 12:00 PM (recess rule violations) and at 5:00 PM (parent behavior ratings) to determine whether Adderall was still effective at times when the effects of Ritalin should have worn off. Parent ratings were also made for evening behavior to assess possible rebound, and side effects ratings were obtained from parents, counselors, and teachers. Parents, counselors, and teachers also rated their perceptions of medication status and whether they recommended the continued use of the medication given that day. Finally, a clinical team made recommendations for treatment taking into account each child's individual response.
Both drugs were routinely superior to placebo and produced dramatic improvements in rates of negative behavior, academic productivity, and staff/parent ratings of behavior. The doses of Adderall that were assessed produced greater improvement than did the assessed doses of Ritalin, particularly the lower dose of Ritalin, on numerous but not all measures. This result suggests that the doses of Adderall used were functionally more potent than those for Ritalin. Adderall was generally superior to the low dose of Ritalin when the effects of Ritalin were wearing off at midday and late afternoon/early evening. The lower dose of Adderall produced effects comparable to those of the higher dose of Ritalin. Both drugs produced low and comparable levels of clinically significant side effects. Staff clinical recommendations for continued medication favored Adderall three to one. Almost 25% of the study participants were judged to be nonresponders by the clinical team, presumably because of their large beneficial response to the concurrent behavioral intervention and minimal incremental benefit from medication.
This is the first investigation to assess comparable doses of Adderall and Ritalin directly. (ABSTRACT TRU
很少有研究关注阿得拉(夏尔-里奇伍德公司,肯塔基州佛罗伦萨)治疗注意缺陷多动障碍(ADHD)儿童的疗效,且尚无研究将其与标准剂量的利他林(诺华制药公司,新泽西州东哈嫩)进行比较。据认为,阿得拉的半衰期比利他林长,可能会减少利他林服用4或5小时后出现的疗效丧失。我们在一项急性研究中比较了两种剂量的利他林和阿得拉治疗儿童ADHD的效果,并评估了药物的时效过程。
受试者内、双盲、安慰剂对照、交叉设计,为期6周。与我们之前的研究一样,药物变化在数天内按随机顺序每日进行。
纽约州立大学布法罗分校为期八周的工作日(每天9小时)暑期治疗项目,采用强化行为治疗项目,包括积分系统和家长培训。
25名儿童(21名男孩和4名女孩),通过标准化结构化访谈和评分量表诊断为ADHD,平均年龄9.6岁,88%为白种人,智力中等,无任何会妨碍试用兴奋剂药物的疾病。13名儿童合并对立违抗障碍,另外8名合并品行障碍。
儿童随机接受10毫克利他林、17.5毫克利他林、7.5毫克阿得拉、12.5毫克阿得拉或安慰剂,每日两次(上午7:45和下午12:15),条件每日变化,共24天。
娱乐和课堂环境中的每日行为发生率,以及辅导员、教师和家长的标准化评分,在每个儿童的每个条件下按天进行平均并比较。通过计算每个儿童的安慰剂减去药物的平均差值除以安慰剂标准差来计算受试者内药物效应的相对大小,并在每日首次服药(上午7:45)至下午5:00之间每小时进行比较,以评估两种药物的时效过程。在下午12:00(课间违规)和下午5:00(家长行为评分)进行测量,以确定在利他林效果应该消退时阿得拉是否仍然有效。还对家长进行了夜间行为评分以评估可能的反跳,并从家长、辅导员和教师处获得副作用评分。家长、辅导员和教师还对他们对药物状态的看法以及他们是否建议继续使用当天服用的药物进行了评分。最后,临床团队根据每个儿童的个体反应提出治疗建议。
两种药物在常规情况下均优于安慰剂,并在负面行为发生率、学业成绩以及工作人员/家长行为评分方面产生了显著改善。在所评估的阿得拉剂量比所评估的利他林剂量产生了更大的改善,特别是在许多但并非所有指标上,低剂量的利他林更是如此。这一结果表明,所使用的阿得拉剂量在功能上比利他林的剂量更有效。当中午以及下午晚些时候/傍晚利他林效果消退时,阿得拉总体上优于低剂量的利他林。较低剂量的阿得拉产生的效果与较高剂量的利他林相当。两种药物产生的临床显著副作用水平较低且相当。工作人员关于继续用药的临床建议中,支持阿得拉的与支持利他林的比例为三比一。临床团队判定近25%的研究参与者为无反应者大概由于他们对同时进行的行为干预有较大的有益反应,而药物带来的增量益处最小。
这是首次直接评估阿得拉和利他林可比剂量的研究。