联合使用兴奋剂和胍法辛治疗注意力缺陷多动障碍：一项对照比较研究。
Combined Stimulant and Guanfacine Administration in Attention-Deficit/Hyperactivity Disorder: A Controlled, Comparative Study.
作者信息
McCracken James T, McGough James J, Loo Sandra K, Levitt Jennifer, Del'Homme Melissa, Cowen Jennifer, Sturm Alexandra, Whelan Fiona, Hellemann Gerhard, Sugar Catherine, Bilder Robert M
机构信息
David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
出版信息
J Am Acad Child Adolesc Psychiatry. 2016 Aug;55(8):657-666.e1. doi: 10.1016/j.jaac.2016.05.015. Epub 2016 Jun 3.
OBJECTIVE
Because models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability.
METHOD
An 8-week, double-blind, 3-arm, comparative trial randomized 7- to 14-year-olds with DSM-IV ADHD to GUAN (1-3 mg/day), DMPH (5-20 mg/day), or a combination (COMB) with fixed-flexible dosing. Outcome measures were the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Data on adverse events and safety measures were obtained.
RESULTS
A total of 207 participants were randomized and received drug. Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total (p = .0001) and inattentive symptoms (p = .0001). COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies (DMPH: p = .05; f(2) = .02; and GUAN: p = .02; f(2) = .02), and was associated with a greater positive response rate by CGI-I (p = .01). No serious cardiovascular events occurred. Sedation, somnolence, lethargy, and fatigue were greater in both guanfacine groups. All treatments were well tolerated.
CONCLUSION
COMB showed consistent evidence of clinical benefits over monotherapies, possibly reflecting advantages of greater combined dopaminergic and α2A agonism. Adverse events were generally mild to moderate, and COMB treatment showed no differences in safety or tolerability.
CLINICAL TRIAL REGISTRATION INFORMATION
Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); http://clinicaltrials.gov/; NCT00429273.
目的
由于注意力缺陷多动障碍（ADHD）治疗模型强调增强多巴胺能和去甲肾上腺素能信号传导的益处，增强D1和α2A激动作用的策略可能会产生更强的临床和认知反应。本研究检验了以下假设：多巴胺和去甲肾上腺素能激动剂、缓释d-甲基苯丙胺（DMPH）与α2A受体激动剂胍法辛（GUAN）的联合作用在临床上优于单一疗法，且耐受性相同。
方法
一项为期8周的双盲、三臂、对照试验，将7至14岁符合DSM-IV标准的ADHD患儿随机分为三组，分别接受胍法辛（1-3毫克/天）、DMPH（5-20毫克/天）或固定-灵活剂量的联合治疗（COMB）。观察指标为ADHD评定量表第四版（ADHD-RS-IV）和临床总体印象改善量表（CGI-I）。收集不良事件和安全指标数据。
结果
共有207名参与者被随机分组并接受药物治疗。分析显示，治疗组在ADHD-RS-IV总分（p = 0.0001）和注意力不集中症状方面（p = 0.0001）有显著的主效应。与单一疗法相比，联合治疗在ADHD-RS-IV注意力不集中分量表得分上的降低幅度虽小但始终更大（DMPH：p = 0.05；f(2) = 0.02；胍法辛：p = 0.02；f(2) = 0.02），且与CGI-I更高的阳性反应率相关（p = 0.01）。未发生严重心血管事件。两个胍法辛组的镇静、嗜睡、乏力和疲劳情况更严重。所有治疗的耐受性均良好。
结论
与单一疗法相比，联合治疗显示出持续的临床益处，这可能反映了多巴胺能和α2A激动作用增强的优势。不良事件一般为轻至中度，联合治疗在安全性或耐受性方面无差异。
临床试验注册信息
注意力缺陷多动障碍儿童的单药治疗与联合药物治疗（项目1）；http://clinicaltrials.gov/；NCT00429273
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