Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, P.O. Box 12 21 20, 68072, Mannheim, Germany.
Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, Gothenburg University, Göteborg, Sweden.
CNS Drugs. 2018 May;32(5):455-467. doi: 10.1007/s40263-018-0514-8.
Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents.
The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder.
Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging.
The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on-treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on-treatment assessment from a higher weight category at baseline. At the last on-treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher.
Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS.
NCT01328756.
治疗注意缺陷/多动障碍的兴奋剂药物具有安全有效的使用历史；然而，人们担心它们可能会影响儿童和青少年的生长轨迹。
本研究旨在评估二甲磺酸赖右苯丙胺对患有注意缺陷/多动障碍的儿童和青少年的体重、身高、体重指数和青春期发育的长期影响。
6-17 岁患有注意缺陷/多动障碍的儿童和青少年在这项为期 2 年的开放性标签安全性和疗效研究中服用开放性标签的二甲磺酸赖右苯丙胺（30、50 或 70mg/天）。安全性评估包括治疗中出现的不良事件、体重、身高和体重指数的测量，以及使用 Tanner 分期自我报告的青春期状态。
安全性分析人群包括所有入组的参与者（N=314），其中 191 人（60.8%）完成了研究。63 名参与者（20.1%）报告体重下降是治疗中出现的不良事件，有两名参与者（0.6%）因体重下降的治疗中出现的不良事件而停止研究。两名参与者报告生长迟缓为治疗中出现的不良事件。从基线到最后一次治疗评估，平均体重增加 2.1kg（标准差 5.83），身高增加 6.1cm（标准差 4.90），体重指数下降 0.5kg/m（标准差 1.72）。研究的前 36 周，平均体重、身高和体重指数 z 分数下降，然后稳定。从基线到最后一次治疗评估，平均 z 分数的变化在体重、身高和体重指数上均显著小于零（分别为-0.51、-0.24 和-0.59；名义 p<0.0001）。体重 z 分数< -1 的参与者比例从基线时的 5.1%（基线）到第 84 周时的 22.1%（第 84 周），身高 z 分数从基线时的 8.2%（基线）到第 96 周时的 12.6%（第 96 周），体重指数 z 分数从基线时的 8.3%（基线）到第 96 周时的 28.8%（第 96 周）。13 名参与者（4.1%）从基线时较高的体重类别转移到最后一次治疗评估时的体重低于第 5 百分位。在最后一次治疗评估时，大多数参与者仍处于基线 Tanner 阶段或已经上升到更高的阶段。
这项对二甲磺酸赖右苯丙胺治疗 2 年后与生长结果相关的全面研究结果与兴奋剂药物的先前研究一致。虽然研究过程中平均体重和身高增加，但平均体重、身高和体重指数 z 分数有一个短暂的轻微下降。在体重和体重指数最低类别中，参与者比例略有增加，突出了定期监测体重和身高的重要性。没有证据表明青春期延迟。临床试验。
NCT01328756。
