兴奋剂、胍法辛及联合治疗对儿童和青少年注意力缺陷/多动障碍的认知影响
Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.
作者信息
Bilder Robert M, Loo Sandra K, McGough James J, Whelan Fiona, Hellemann Gerhard, Sugar Catherine, Del'Homme Melissa, Sturm Alexandra, Cowen Jennifer, Hanada Grant, McCracken James T
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; UCLA College of Letters and Science.
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):667-73. doi: 10.1016/j.jaac.2016.05.016. Epub 2016 Jun 7.
OBJECTIVE
Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD.
METHOD
Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables.
RESULTS
The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group.
CONCLUSION
Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD.
CLINICAL TRIAL REGISTRATION INFORMATION
Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.
目的
精神兴奋剂在减轻与注意力缺陷多动障碍（ADHD）相关的认知功能障碍方面部分有效。作为一种替代治疗药物，胍法辛的认知作用了解甚少。鉴于其对α2A受体的独特作用，胍法辛相对于兴奋剂可能具有不同或互补的作用。本研究测试了兴奋剂和胍法辛单一疗法以及联合治疗对ADHD中重要认知功能的影响。
方法
患有ADHD的儿童（n = 182；年龄7 - 14岁）完成了一项为期8周的双盲、随机、对照试验，试验分为3组：右旋甲基苯丙胺（DMPH）、胍法辛（GUAN）或DMPH与GUAN联合治疗（COMB）。一个非临床比较组（n = 93）进行了基线测试，其中一部分在8周后重新进行了测试（n = 38）。分析检查了由20个变量构建的4个认知领域（工作记忆、反应抑制、反应时间和反应时间变异性）的治疗效果。
结果
与非临床比较组相比，ADHD组的工作记忆受损（效应量 = -0.53标准差单位）。各治疗方法对工作记忆的影响不同，但对其他认知领域无差异。联合治疗比胍法辛单一治疗更能改善工作记忆，但并不显著优于单独使用右旋甲基苯丙胺。相对于比较组，治疗并未使ADHD最初的缺陷完全恢复正常。
结论
与安慰剂或单独使用胍法辛相比，右旋甲基苯丙胺与胍法辛联合治疗在工作记忆方面有更大改善，但联合治疗并不优于单独使用右旋甲基苯丙胺，且未扩展到其他认知领域。虽然胍法辛可能是精神兴奋剂有用的附加治疗药物，但似乎需要其他策略来使ADHD的认知功能恢复正常。
临床试验注册信息
注意缺陷多动障碍儿童的单一药物与联合药物治疗；http://clinicaltrials.gov/；NCT00429273 。
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