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Randomized Controlled Trial
. 2015 Jan;56(1):40-8.
doi: 10.1111/jcpp.12272. Epub 2014 Jun 19.

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

Anne-Claude V Bédard  1 , Mark A Stein, Jeffrey M Halperin, Beth Krone, Estrella Rajwan, Jeffrey H Newcorn
Affiliations
Randomized Controlled Trial

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

Anne-Claude V Bédard et al. J Child Psychol Psychiatry. 2015 Jan.

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: One hundred and two 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 (premedication, postmedication) 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 = .03), RTSD (p = .001), and omission errors (p = .01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD, and omission errors more than ATX (p < .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.

Keywords: Attention-deficit/hyperactivity disorder; atomoxetine; attention; methylphenidate; vigilance.

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Conflict of interest statement

Conflict of interest statement: M.A.S. has received research support from Shire Pharmaceuticals, and is a consultant/advisor for Alcobra, GencoSciences, and Novartis. J.H.N. has received research support from Shire Pharmaceuticals; he is an advisor and/or consultant for Alcobra, BioBehavioral Diagnostics, Enzymotec, GencoSciences, Sunovion, and Shire Pharmaceuticals. The rest of the authors have declared that they have no potential or competing conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic of study design.
Fig. 2
Fig. 2
Schematic of study completers.
Fig. 3
Fig. 3
Performance on Conners CPT-II by treatment (Atomoxetine, Methylphenidate) and time (PreMed, PostMed). Conners CPT-II performance for (a) commission errors, (b) omission errors, (c) reaction time (RT), and (d) reaction time variability (RT variability).
See this image and copyright information in PMC

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