Response inhibition and emotional cognition improved by atomoxetine in children and adolescents with ADHD: The ACTION randomized controlled trial

Griffiths, Kristi R.; Leikauf, John E.; Tsang, Tracey W.; Clarke, Simon; Hermens, Daniel F.; Efron, Daryl; Williams, Leanne M.; Kohn, Michael R.

doi:10.1016/j.jpsychires.2018.03.009

Cited by 30Attention Deficit Hyperactivity DisorderDevelopmental and Educational NeuropsychologyChild and Adolescent Psychosocial and Emotional Development

Response inhibition and emotional cognition improved by atomoxetine in children and adolescents with ADHD: The ACTION randomized controlled trial

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Griffiths, Kristi R., Leikauf, John E., Tsang, Tracey W., Clarke, Simon, Hermens, Daniel F., Efron, Daryl, Williams, Leanne M., Kohn, Michael R.·2018·Journal of Psychiatric Research

DOI 10.1016/j.jpsychires.2018.03.009PMC PMC9148271

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Abstract

Although the non-stimulant medication atomoxetine is effective for attention-deficit hyperactivity disorder (ADHD) in children and adolescents, there are still significant gaps in our knowledge about whether atomoxetine improves anxiety symptoms or cognition in children. Furthermore, while cognition has been proposed as an intermediate phenotype for ADHD dysfunction, the relationships between clinical and cognitive outcomes are not yet understood. We addressed these knowledge gaps in a controlled trial using objective assessments of both general and emotional cognitive functions implicated in ADHD and in anxiety, which commonly co-occurs with ADHD. A total of 136 children and adolescents with ADHD (ages 6-17years; 80% male; 31.6% with a comorbid anxiety disorder) were enrolled in a randomized double-blind, placebo-controlled, cross-over trial of 6-weeks treatment with atomoxetine. Of these, 109 completed the second cross-over phase. Selected cognitive domains associated with ADHD and anxiety disorders (Sustained attention, response inhibition and fearful face identification) were assessed using a normed, computerized test battery. Symptom outcomes were assessed by parent reports on the ADHD Rating Scale-IV and Conners' Anxious-Shy subscale. For completers, atomoxetine caused a greater improvement in the primary cognitive outcomes of response inhibition and fear identification compared to placebo, but not in sustained attention. Atomoxetine also improved ADHD and anxiety symptoms. Anxiety symptoms improved most for ADHD and anxiety disorder combined, but presence of an anxiety disorder did not moderate any other outcomes. Changes in cognitive and clinical outcomes were not correlated. These findings contribute to the foundations of measurement-based treatment planning and offer targets for probing the mechanisms of atomoxetine action.

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“…indicated a moderate decrease in errors of omission and commission on the Continuous Performance Test after intervention with atom-oxetine (CE, ES = 0.50; OE, ES = 0.70) (Wehmeier et al., 2012), as well as a moderately improved performance on the Go/No-Go task ( d = 0.42) (Griffiths et al., 2018).”
MethodInfluential
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Yacoub, M., Smith, S., Abbas, B., Iqbal, F., Jazieh, C., Shaer, N. S. H. A., Luk, C., & Syed, N. I. (2025) · Cells · doi:10.3390/cells14171367 · Cited by 12 · see citing works
“This includes improvements in pattern and spatial recognition memory [309], reduced anxiety symptoms [310,311], and improved response inhibition [312].”
Atomoxetine and circadian gene expression in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder
Faltraco, F., Palm, D., Uzoni, A., Simon, F. A. J., Tucha, O. M., & Thome, J. (2021) · Journal of Neural Transmission · doi:10.1007/s00702-021-02373-5 · Cited by 8 · see citing works
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“Similar to methylphenidate, atomoxetine is also considered to improve response inhibition and attention.(18) Interestingly, it was reported that trichotillomania symptoms improvedwith atomoxetine treatment in an adolescentwithADHD.”
Background
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“…demonstrated that certain cognitive processes may benefit from pharmacological treatments, including response inhibition (Coghill et al., 2014a; Griffiths et al., 2018; Lee et al., 2022), working memory (Coghill et al., 2014a), non-executive aspects of short-term memory (Coghill et al., 2014a,…”
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“Although the main use and popularity of atomoxetine are generally attributed to the alleviation of ADHD, thereby rendering cognitive enhancement [52], it is understandable that the functions of atomoxetine are critically dependent on norepinephrine dynamics and noradrenergic receptor status, which can vary from diseas…”
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Self-citation
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A systematic review of the use of atomoxetine for management of comorbid anxiety disorders in children and adolescents with attention-deficit hyperactivity disorder
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ATOMOXETINE TREATMENT FOR PEDIATRIC PATIENTS WITH ADHD AND COMORBID ANXIETY
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A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): Rationale and design
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Self-citation
Atomoxetine Treatment for Pediatric Patients With Attention-Deficit/Hyperactivity Disorder With Comorbid Anxiety Disorder
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Effects of atomoxetine on ADHD symptoms, anxiety and cognition: outcomes of the randomized controlled ACTION trial
Kohn, M. R., Griffiths, K. R., Clarke, S. P., Tsang, T. W., Hermens, D. F., Efron, D., Clark, C. R., Lamb, C., Deloughery, M., & Williams, L. M. (2015) · F1000Research · doi:10.7490/f1000research.1098188.1
Self-citation

Authors: Griffiths, K. R., Leikauf, J. E., Tsang, T. W., Clarke, S., Hermens, D. F., Efron, D., Williams, L. M., & Kohn, M. R.
Affiliations: The University of Sydney (AU)
Stanford University (US)
University of the Sunshine Coast (AU)
Royal Children's Hospital (AU)
Corresponding author: Williams, Leanne M.
ORCID: Griffiths, Kristi R.
Leikauf, John E.
Tsang, Tracey W.
Clarke, Simon
Hermens, Daniel F.
Efron, Daryl
Williams, Leanne M.
Kohn, Michael R.
Venue: Journal of Psychiatric Research
Publisher: Elsevier BV
Published: 2018-07
Volume: 102
Pages: 57-64
ISSN: 0022-3956 (ISSN-L)
DOI: 10.1016/j.jpsychires.2018.03.009
PMC: PMC9148271
OpenAlex: W2794800338
Cited by: 29
References: 57
Citations by year: 2026: 4 · 2025: 4 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 1
FWCI: 1.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Psychiatric Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Health and Medical Research Council (457424, 1122842)
Westmead Medical Research Foundation
National Institute of Mental Health training (5 T32 MH19908 22)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Keywords: atomoxetine, attention deficit hyperactivity disorder, response inhibition, emotional cognition, sustained attention, anxiety symptoms, comorbid anxiety disorders, non-stimulant medication, endophenotypes, children and adolescents
MeSH terms: Atomoxetine Hydrochloride, Adolescent, Anxiety Disorders, Attention Deficit Disorder with Hyperactivity, Child, Cognition Disorders, Double-Blind Method, Female, Humans, Inhibition, Psychological, Male, Psychiatric Status Rating Scales, Cohort Studies, Treatment Outcome, Cross-Over Studies, Adrenergic Uptake Inhibitors

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Response inhibition and emotional cognition improved by atomoxetine in children and adolescents with ADHD: The ACTION randomized controlled trial

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