A Randomized Double-Blind Study of Atomoxetine Versus Placebo for Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Autism Spectrum Disorder
Open accessAbstract
Objective The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. Method In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks. The primary endpoint was the ADHD Rating Scale (ADHD-RS) score; secondary endpoints were the Clinical Global Impression of ADHD-Improvement (CGI-I) and the Conners Teacher Rating Scale-Revised: Short Form (CTRS-R:S) score. Results Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6; after 8 weeks, mixed-effect model repeated-measure means were 31.6 (95% confidence interval 29.2-33.9) and 38.3 (36.0-40.6), respectively, with a difference in least square means of -6.7 (-10.0 to -3.4; p < .001). The CTRS-R:S Hyperactivity subscore also improved significantly for atomoxetine compared with placebo, but not the other CTRS-R:S subscores. However, there were not significantly more patients on atomoxetine (20.9%) who improved much, or very much according to the CGI-I, than on placebo (8.7%; p = 0.14). Adverse events (mostly nausea, decrease in appetite, fatigue, and early morning awakening) were reported in 81.3% of atomoxetine patients and 65.3% of placebo patients (p > .1). There were no serious adverse events. Conclusions Atomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated. Adverse events in this study were similar to those in other studies with ADHD patients without ASD. Clinical trial registration information-A Randomized Double-Blind Study of Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD; www.clinicaltrials.gov; NCT00380692.
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The active group had an average 8.2-point reduction in ADHD Rating Scale total scores from baseline, compared to a 1.2-point decrease in the placebo group.
“The active group had an average 8.2-point reduction in ADHD Rating Scale total scores from baseline, compared to a 1.2-point decrease in the placebo group.”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [89]
Commonly reported side effects included nausea, reduced appetite, fatigue, and early morning awakenings.
“Commonly reported side effects included nausea, reduced appetite, fatigue, and early morning awakenings [89].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [89]
This reflects a smaller magnitude of the effect of atomoxetine for ADHD in children with ASD than that reported in studies of atomoxetine in typically developing children with ADHD.
“This reflects a smaller magnitude of the effect of atomoxetine for ADHD in children with ASD than that reported in studies of atomoxetine in typically developing children with ADHD.”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [89]
A RCT in 97 children, ages 6-17 years, with ASD and ADHD found that atomoxetine improved ADHD symptoms.
“A RCT in 97 children, ages 6–17 years, with ASD and ADHD found that atomoxetine improved ADHD symptoms [89].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [89]
In this trial, there was no significant difference in the number of patients who were "much improved" or "very much improved" on the medication compared to placebo, as measured by the CGI-I.
“In this trial, there was no significant difference in the number of patients who were “much improved” or “very much improved” on the medication compared to placebo, as measured by the CGI-I.”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [89]
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“A RCT in 97 children, ages 6–17 years, with ASD and ADHD found that atomoxetine improved ADHD symptoms [89].”
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- Authors
- Harfterkamp, M., van de Loo-Neus, G., Minderaa, R. B., van der Gaag, R.-J., Escobar, R., Schacht, A., Pamulapati, S., Buitelaar, J. K., & Hoekstra, P. J.
- Affiliations
- University Medical Center Groningen (NL)
- Radboud University Nijmegen (NL)
- Corresponding author
- Harfterkamp, Myriam
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 51
- Issue
- 7
- Pages
- 733-741
- ISSN
- 0890-8567 (ISSN-L)
- OpenAlex
- W2115061863
- Cited by
- 171
- References
- 3
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 13 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 15 · 2019: 10 · 2018: 9 · 2017: 14 · 2016: 23 · 2015: 17 · 2014: 15 · 2013: 10 · 2012: 3
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Eli Lilly and Company
- European Commission
- Rijksuniversiteit Groningen
- ZonMw
- Radboud Universiteit
- Universitair Medisch Centrum Groningen
- Radboud Universitair Medisch Centrum
- Servier
- National Institute of Mental Health
- UCB Pharma
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
- Keywords
- atomoxetine, autism spectrum disorder, attention deficit hyperactivity disorder, ADHD symptoms, stimulant medication, children, hyperactivity, adverse events, drug tolerability, ADHD Rating Scale
- MeSH terms
- Atomoxetine Hydrochloride, Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child Development Disorders, Pervasive, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Personality Assessment, Propylamines, Psychometrics, Comorbidity, Adrenergic Uptake Inhibitors
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