Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention‐deficit/hyperactivity disorder

Abstract

Background This study examined the effects of atomoxetine (ATX) and OROS methylphenidate (MPH) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder (ADHD). It was hypothesized that performance would be improved by both treatments, but response profiles would differ because the medications work via different mechanisms. Methods 102 youth (77 male; mean age = 10.5 +/− 2.7 years) with ADHD received ATX (1.4 +/− 0.5 mg/kg) and MPH (52.4 +/− 16.6 mg) in a randomized, double-blind, crossover design. Medication was titrated in 4–6-week blocks separated by a 2-week placebo washout. Inhibitory control and attention measures were obtained at baseline, following washout, and at the end of each treatment using Conners’ Continuous Performance Test II (CPT-II), which provided age-adjusted T-scores for reaction time (RT), reaction time variability (RT variability), and errors. Repeated measures analyses of variance were performed, with Time (pre-medication, post-medication) and Treatment type (ATX, MPH) entered as within-subject factors. Data from the two treatment blocks were checked for order effects and combined if order effects were not present. Clinical trial registration Clinicaltrials.gov:NCT00183391 Results Main effects for Time on RT (p = 0.03), RTSD (p = 0.001) and omission errors (p = 0.01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD and omission errors more than ATX (p <0.05). Changes in performance with treatment did not correlate with changes in ADHD symptoms. Conclusions MPH has greater effects than ATX on CPT measures of sustained attention in youth with ADHD. However, the dissociation of cognitive and behavioral change with treatment indicates that CPT measures cannot be considered proxies for symptomatic improvement. Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated.

ADHD History of the Concept: the Case of the Continuous Performance Test

“…In addition, the CPT was used for the evaluation of improved pharmaceutical dosage forms of MPH, e.g., extended controlled-release capsules [39]. It was recently demonstrated that atomoxetine (ATX, a nonstimulant selective norepinephrine reuptake inhibitor used for the treatment of ADHD in children and adults) may lead to improved CPT performance, albeit of a smaller magnitude than with MPH [40,41].…”

Transcranial direct current brain stimulation decreases impulsivity in ADHD

“…ADHD patients make more false positive errors than healthy adults, and these errors are sensitive to the effects of stimulant treatment in ADHD patients [22–25]. Furthermore, performance on this task is sensitive to effects of methylphenidate, an efficacious ADHD treatment [24–27]. Stimulant medications such as methylphenidate decrease false positive error rates following three weeks of treatment, with a medium-to-large effect size (η 2 =.21) [26].…”

Intact Stimulus–Response Conflict Processing in ADHD—Multilevel Evidence and Theoretical Implications

“…Interestingly, treatment approaches like neurofeedback have been shown to lead to improvements in inhibitory control and to decreases in impulsivity in patients with ADHD [74,75]. From the point of view of medication, it has been suggested that atomoxetine (frequently used as second-line medication) may be more effective in reducing impulsivity than is the case for methylphenidate (first-line treatment), which may in turn be more beneficial in terms of reducing inattention [76,77]. Importantly, only atomoxetine has been shown to increase prefrontal activation during a Stroop task [78].…”