Child and Adolescent Mental Health Centre, Research Unit, Mental Health Services, The Capital Region of Denmark, Hellerup, Denmark.
The Research Unit, Department of Palliative Medicine, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, The Capital Region of Denmark, Copenhagen, Denmark.
PLoS One. 2021 Oct 21;16(10):e0253727. doi: 10.1371/journal.pone.0253727. eCollection 2021.
Randomized placebo-controlled trials have reported efficacy of methylphenidate (MPH) for Attention-deficit/hyperactivity disorder (ADHD); however, selection biases due to strict entry criteria may limit the generalizability of the findings. Few ecologically valid studies have investigated effectiveness of MPH in representative clinical populations of children. This independently funded study aims to describe treatment responses and their predictors during the first 12 weeks of MPH treatment using repeated measurements of symptoms and adverse reactions (ARs) to treatment in 207 children recently diagnosed with ADHD. The children were consecutively included from the Child and Adolescent Mental Health Centre, Mental Health Services, The Capital Region of Denmark. The children (mean age, 9.6 years [range 7-12], 75.4% males) were titrated with MPH, based on weekly assessments of symptoms (18-item ADHD-rating scale scores, ADHD-RS-C) and ARs. At study-end 187 (90.8%) children reached a mean end-dose of 1.0 mg/kg/day. A normalisation/borderline normalisation on ADHD-RS-C was achieved for 168 (81.2%) children on the Inattention and/or the Hyperactivity-Impulsivity subscale in week 12, and 31 (15.0%) children were nonresponders, which was defined as absence of normalisation/borderline normalisation (n = 19) or discontinuation due to ARs (n = 12), and eight (3.8%) children dropped out from follow-up. Nonresponders were characterised by more severe symptoms of Hyperactivity-Impulsivity and global impairment before the treatment. ARs were few; the most prominent were appetite reduction and weight loss. A decrease in AR-like symptoms during the treatment period questions the validity of currently available standard instruments designed to measure ARs of MPH. This ecologically valid observational study supports prior randomized placebo-controlled trials; 81.2% of the children responded favourably in multiple domains with few harmful effects to carefully titrated MPH. Clinical trial registration: ClinicalTrials.gov with registration number NCT04366609.
随机安慰剂对照试验已经报告了哌醋甲酯（MPH）治疗注意缺陷/多动障碍（ADHD）的疗效；然而，由于严格的纳入标准导致的选择偏倚可能限制了研究结果的普遍性。很少有生态有效的研究调查了 MPH 在具有代表性的儿童临床人群中的有效性。这项独立资助的研究旨在使用 207 名最近被诊断为 ADHD 的儿童在接受 MPH 治疗的前 12 周内对症状和治疗不良反应（ARs）进行重复测量，描述治疗反应及其预测因素。这些儿童是从丹麦首都大区精神卫生服务中心儿童和青少年心理健康中心连续纳入的。这些儿童（平均年龄 9.6 岁[范围 7-12]，75.4%为男性）根据每周对症状（18 项 ADHD 评定量表评分，ADHD-RS-C）和 ARs 的评估进行 MPH 滴定。在研究结束时，187 名（90.8%）儿童达到 1.0mg/kg/天的平均终剂量。在第 12 周，168 名（81.2%）儿童在注意力不集中和/或多动冲动子量表上达到 ADHD-RS-C 的正常化/边界正常化，31 名（15.0%）儿童无反应，定义为无正常化/边界正常化（n=19）或因 ARs 停药（n=12），8 名（3.8%）儿童从随访中退出。无反应者在治疗前表现出更严重的多动冲动症状和整体受损。不良反应很少；最突出的是食欲下降和体重减轻。在治疗期间 AR 样症状的减少对目前用于测量 MPH 不良反应的现有标准工具的有效性提出了质疑。这项生态有效的观察性研究支持先前的随机安慰剂对照试验；81.2%的儿童在多个领域有良好的反应，只有少数儿童对仔细滴定的 MPH 有不良影响。临床试验注册：ClinicalTrials.gov，注册号 NCT04366609。
