Hammerness Paul, Georgiopoulos Anna, Doyle Robert L, Utzinger Linsey, Schillinger Mary, Martelon Marykate, Brodziak Kerry, Biederman Joseph, Wilens Timothy E
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School , Boston Massachusetts, USA.
J Child Adolesc Psychopharmacol. 2009 Oct;19(5):493-9. doi: 10.1089/cap.2008.0126.
The aim of this study was to evaluate the tolerability of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit/hyperactivity disorder (ADHD).
This was a two-phase, 7-week, open study in children aged 6-17 years. Phase 1 initiated ATMX for a minimum of 4 weeks. Phase 2 entered partial responders to ATMX and added OROS MPH to their regimen. Safety was assessed using blood pressure and heart rate measurements, electrocardiogram readings, AEs, laboratories, and ATMX levels.
Fifty subjects who were partial responders to ATMX received the combination therapy, with 41 subjects completing the entire protocol. As reported elsewhere (Wilens et al., 2009 ), OROS MPH added to partial responders of ATMX was accompanied by a 40% reduction in the ADHD rating scale score and improvements in executive functioning. However, the combination of ATMX plus OROS MPH was associated with greater rates of insomnia, irritability, and loss of appetite compared to ATMX alone. A small significant increase in diastolic blood pressure was observed during adjunctive OROS MPH, with no clinically meaningful changes in electrocardiogram (ECG) parameters during the study. ATMX levels and liver function tests did not significantly change during the combination treatment.
Adjunct OROS MPH in ATMX partial responders yielded an additive adverse effect burden in this short-term study. Further controlled research with larger samples of children is warranted.
本研究旨在评估对托莫西汀（ATMX）治疗注意力缺陷多动障碍（ADHD）部分反应不佳的儿童加用奥罗控释哌甲酯（MPH）的耐受性。
这是一项针对6至17岁儿童的为期7周的两阶段开放性研究。第一阶段开始使用ATMX至少4周。第二阶段纳入对ATMX部分反应不佳的儿童，并在其治疗方案中加用奥罗控释MPH。通过测量血压和心率、心电图读数、不良事件、实验室检查以及ATMX水平来评估安全性。
50名对ATMX部分反应不佳的受试者接受了联合治疗，其中41名受试者完成了整个方案。如其他地方所报道（Wilens等人，2009年），对ATMX部分反应不佳的儿童加用奥罗控释MPH后，ADHD评定量表评分降低了40%，执行功能也有所改善。然而，与单独使用ATMX相比，ATMX加奥罗控释MPH的联合治疗导致失眠、易怒和食欲不振的发生率更高。在加用奥罗控释MPH期间观察到舒张压有小幅显著升高，研究期间心电图（ECG）参数无临床意义上的变化。联合治疗期间ATMX水平和肝功能检查无显著变化。
在本短期研究中，对ATMX部分反应不佳的儿童加用奥罗控释MPH产生了额外的不良反应负担。有必要对更多儿童样本进行进一步的对照研究。
