Gilbert Donald L, Ridel Keith R, Sallee Floyd R, Zhang Jie, Lipps Tara D, Wassermann Eric M
Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH 45229, USA.
Neuropsychopharmacology. 2006 Feb;31(2):442-9. doi: 10.1038/sj.npp.1300806.
Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.
兴奋剂和去甲肾上腺素（NE）再摄取抑制剂药物在神经元水平上具有不同的作用，但两者都能减轻注意力缺陷多动障碍（ADHD）的症状。为了了解它们的共同生理作用，从而深入了解ADHD治疗的神经生物学机制，我们比较了兴奋剂哌甲酯（MPH）和NE摄取抑制剂托莫西汀（ATX）对人类皮层抑制性和兴奋性过程的影响。在一项随机、双盲交叉试验中，9名健康的右利手成年人在相隔1周的访视中分别口服30mg MPH和60mg ATX的单剂量药物。我们使用运动皮层的配对和单次经颅磁刺激（TMS）来测量给药前后抑制性（3ms）和易化性（10ms）刺激间隔（ISI）下的条件性和非条件性运动诱发电位幅度。数据采用重复测量、混合模型回归进行分析。我们还使用荟萃分析软件分析了我们的研究结果和已发表的文献，以估计兴奋剂和NE再摄取抑制剂对这些TMS测量指标的治疗效果。治疗前无显著差异，治疗顺序也无影响。两种药物均使易化作用显著增加，抑制作用降低。ATX和MPH的作用无显著差异。已发表研究的汇总估计显示，兴奋剂和NE再摄取抑制剂的结果相似。总之，在健康成年人中，用于治疗ADHD的兴奋剂和非兴奋剂药物均可降低皮层抑制并增加皮层易化作用。先前已证明ADHD患者的皮层抑制异常，其可能在产生行为病理学方面起关键作用。
