Huss Michael, Sikirica Vanja, Hervas Amaia, Newcorn Jeffrey H, Harpin Valerie, Robertson Brigitte
Child and Adolescent Psychiatry, Johannes Gutenberg University Mainz, Mainz, Germany.
Global Health Economics, Outcomes Research and Epidemiology, Shire, Wayne, PA, USA.
Neuropsychiatr Dis Treat. 2016 May 5;112:1085-101. doi: 10.2147/NDT.S94158. eCollection 2016.
Guanfacine extended release (GXR) and atomoxetine (ATX) are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD). As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT), in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS). Participants were 6-17 years old with ADHD Rating Scale version IV (ADHD-RS-IV) scores ≥32 and Clinical Global Impressions - Severity scores ≥4. RCT participants received dose-optimized GXR (1-7 mg/day), ATX (10-100 mg/day), or placebo for 10-13 weeks. RWS participants received dose-optimized GXR (1-7 mg/day) for 13 weeks. Participants' last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH); due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most frequent reasons for stopping MPH were lack of effectiveness or side effects. Placebo-adjusted ADHD-RS-IV changes from baseline were significant in participants receiving GXR (prior MPH, -9.8, P<0.001, effect size [ES] 0.85; stimulant-naïve, -7.6, P<0.001, ES 0.65). In ATX-treated participants, significant placebo-adjusted differences were seen in stimulant-naïve (-5.0, P=0.022, ES 0.43) but not prior MPH-treated (-1.8, P>0.05, ES 0.15) participants. More participants met responder criteria with GXR versus placebo, regardless of prior treatment. GXR response was unaffected by prior stimulant treatment; ATX produced improvement only in stimulant-naïve participants relative to placebo. These findings may be relevant to clinical decision-making regarding sequencing of ADHD treatments.
缓释胍法辛（GXR）和托莫西汀（ATX）是用于治疗注意力缺陷多动障碍（ADHD）的非兴奋剂。由于在ADHD治疗中，非兴奋剂通常在使用兴奋剂之后使用，因此在一项随机对照试验（RCT）中，将GXR与先前的兴奋剂治疗进行了比较，该试验将ATX作为对照组，并在一项随机撤药研究（RWS）的开放标签阶段进行了评估。参与者年龄在6至17岁之间，ADHD评定量表第四版（ADHD-RS-IV）得分≥32，临床总体印象-严重程度得分≥4。RCT参与者接受剂量优化的GXR（1至7毫克/天）、ATX（10至100毫克/天）或安慰剂治疗10至13周。RWS参与者接受剂量优化的GXR（1至7毫克/天）治疗13周。在基线时收集参与者入组前最后一次使用的兴奋剂药物及其停药原因。根据先前的兴奋剂暴露情况评估从基线开始的ADHD-RS-IV得分变化和反应者比例。在163名RCT参与者和296名RWS参与者中，之前接受过兴奋剂治疗，其中分别有142名和224名接受过哌甲酯（MPH）治疗；由于参与者数量较少且非MPH治疗的异质性，我们仅报告先前MPH治疗的数据。停用MPH最常见的原因是缺乏疗效或出现副作用。接受GXR治疗的参与者（先前使用过MPH，-9.8，P<0.001，效应大小[ES]0.85；未使用过兴奋剂，-7.6，P<0.001，ES 0.65）从基线开始经安慰剂调整后的ADHD-RS-IV变化具有显著性。在接受ATX治疗的参与者中，未使用过兴奋剂的参与者（-5.0，P=0.022，ES 0.43）经安慰剂调整后有显著差异，但先前使用过MPH治疗的参与者（-1.8，P>0.05，ES 0.15）没有显著差异。与安慰剂相比，无论先前治疗情况如何，更多接受GXR治疗的参与者达到了反应者标准。GXR的反应不受先前兴奋剂治疗的影响；相对于安慰剂而言，ATX仅在未使用过兴奋剂的参与者中产生了改善。这些发现可能与ADHD治疗顺序的临床决策相关。
