Stein Mark A, Sikirica Vanja, Weiss Margaret D, Robertson Brigitte, Lyne Andrew, Newcorn Jeffrey H
Psychiatry and Behavioral Medicine, Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.
GlaxoSmithKline, King of Prussia, PA, USA.
CNS Drugs. 2015 Nov;29(11):953-62. doi: 10.1007/s40263-015-0291-6.
In clinical trials of medications to treat attention-deficit/hyperactivity disorder (ADHD) in children, effects on functional impairment have been less well-studied than changes in ADHD symptoms.
Data regarding functional impairment were analyzed from a multicenter, double-blind, placebo-controlled study of guanfacine extended release (GXR) in children with ADHD, using the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). The correspondence of changes in WFIRS-P scores with symptomatic and global response to GXR treatment was also examined, with treatment response defined by scores on both the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impressions-Improvement Scale (CGI-I).
In this 8-week, double-blind, placebo-controlled, dose optimization study at 47 sites across the USA and Canada, children aged 6-12 years with a diagnosis of ADHD [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and an ADHD-RS-IV score ≥28 and CGI-Severity of Illness Scale score ≥4 at baseline], were randomized 1:1:1 into three groups: GXR AM [GXR (1-4 mg/day) in the morning, placebo in the evening], GXR PM [placebo in the morning, GXR (1-4 mg/day) in the evening], or twice-daily placebo. Parents rated their children on the WFIRS-P at screening, baseline, the end of dose optimization, and at the final on-treatment assessment.
The efficacy population was composed of 333 subjects (GXR AM: n = 107; GXR PM: n = 114; placebo: n = 112). At the final on-treatment assessment, there were significant improvements from baseline in the placebo-adjusted difference in least-squares (LS) mean (95 % confidence interval) WFIRS-P Total scores for both GXR treatment groups combined [GXR all-active: -0.16 (-0.25, -0.07), effect size (ES) = 0.448, P <0.001] and separately [GXR AM: -0.15 (-0.26, -0.05), ES = 0.417, P = 0.004; GXR PM: -0.18 (-0.28, -0.07), ES = 0.478, P = 0.001]. Significant improvements in WFIRS-P domain scores for Family, Learning and School (including Academic Performance and Behavior in School), Social, and Risky Behavior were found for both GXR cohorts compared with placebo. However, the Life Skills and Self-Concept domain scores of the WFIRS-P did not improve with GXR treatment. Post hoc stratification by responder status revealed that significant (P <0.001) improvements in WFIRS-P Total and all domain scores were associated with symptomatic treatment response in the GXR all-active group.
GXR treatment in children with ADHD was associated with reductions in WFIRS-P functional impairment scores compared with placebo, regardless of time of GXR administration. Changes in WFIRS-P scores were congruent with clinical response, as determined by both ADHD symptom reduction and CGI-I scores. CLINICALTRIALS.
NCT00997984.
在治疗儿童注意力缺陷多动障碍（ADHD）药物的临床试验中，相较于ADHD症状的变化，对功能损害的影响研究较少。
使用韦斯功能损害评定量表家长报告版（WFIRS-P），对一项关于缓释胍法辛（GXR）治疗ADHD儿童的多中心、双盲、安慰剂对照研究中的功能损害数据进行分析。同时还研究了WFIRS-P评分变化与GXR治疗的症状性及整体反应的对应关系，治疗反应由ADHD评定量表第四版（ADHD-RS-IV）和临床总体印象改善量表（CGI-I）的评分定义。
在美国和加拿大的47个地点进行的这项为期8周的双盲、安慰剂对照、剂量优化研究中，年龄在6至12岁、诊断为ADHD的儿童[符合《精神障碍诊断与统计手册》第四版，修订版标准，且基线时ADHD-RS-IV评分≥28分和临床总体印象疾病严重程度量表评分≥4分]，按1:1:1随机分为三组：上午服用GXR组[早晨服用GXR（1 - 4毫克/天），晚上服用安慰剂]、下午服用GXR组[早晨服用安慰剂，晚上服用GXR（1 - 4毫克/天）]或每日两次服用安慰剂组。家长在筛查、基线、剂量优化结束时以及最终治疗评估时，对孩子进行WFIRS-P评分。
疗效人群由333名受试者组成（上午服用GXR组：n = 107；下午服用GXR组：n = 114；安慰剂组：n = 112）。在最终治疗评估时，与安慰剂相比，两个GXR治疗组合并后的最小二乘（LS）均值（95%置信区间）WFIRS-P总分经安慰剂调整后的差异有显著改善[GXR全活性组：-0.16（-0.25，-0.07），效应量（ES）= 0.448，P <0.001]，单独来看[上午服用GXR组：-0.15（-0.26，-0.05），ES = 0.417，P = 0.004；下午服用GXR组：-0.18（-0.28，-0.07），ES = 0.478，P = 0.001]。与安慰剂相比，两个GXR队列在WFIRS-P的家庭、学习和学校（包括学业成绩和学校行为）、社交及危险行为领域评分均有显著改善。然而，GXR治疗并未使WFIRS-P的生活技能和自我概念领域评分得到改善。根据反应者状态进行的事后分层显示，GXR全活性组中WFIRS-P总分及所有领域评分的显著（P <0.001）改善与症状性治疗反应相关。
与安慰剂相比，ADHD儿童接受GXR治疗后，WFIRS-P功能损害评分降低，且与GXR给药时间无关。WFIRS-P评分变化与临床反应一致，临床反应由ADHD症状减轻和CGI-I评分共同确定。临床试验注册号：NCT00997984。
