The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis
Open accessAbstract
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.
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Longer-term administration of both methylphenidate and atomoxetine improved MRT, attention and inhibition with statistically comparable small to medium effect sizes.
“Our meta-analysis showed that longer-term administration of both methylphenidate and atomoxetine improved MRT, attention and inhibition with statistically comparable small to medium effect sizes (31).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [31]
The available passage is title and author metadata, with no results section or page. Searches for MRT, attention, inhibition, the two medications, and comparable effect sizes found no passage in our copy that addresses the claimed outcomes. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe lisdexamfetamine effects on RT and CV extend findings that methylphenidate consistently improves RTV and RT in children with ADHD.
“They extend findings of methylphenidate consistently improving RTV and RT in children with ADHD (22, 29–31), with meta-analytic fMRI evidence showing that this may be underpinned neurofunctionally by MPH-induced deactivation of frontal areas of the DMN which is associated with RTV in people with ADHD (75).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [31]
The only passage available from our copy is the paper’s title and author information (no section or page). Searches for methylphenidate, reaction time variability (RTV), and reaction time (RT) found no passage reporting whether these measures improved in children with ADHD. (LLM, conf=0.72)
Experimental — accuracy not yet measuredMethylphenidate both in acute and longer-term dosage has been shown to improve inhibitory measures.
“This was also unexpected as methylphenidate both in acute and longer-term dosage has been shown to improve inhibitory measures (17, 22, 29–31).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [31]
The supplied passage and all retrieved passages contain only the paper’s title and author information, with no findings on inhibitory measures. Searches for acute and chronic methylphenidate effects and response inhibition found no relevant text in the accessible copy, so the claim cannot be checked. (LLM, conf=0.72)
Experimental — accuracy not yet measuredThe study's findings could extend evidence for acute and chronic methylphenidate administration significantly improving timing and attention functions in children with ADHD including the same tasks.
“These findings could extend evidence for acute and chronic methylphenidate administration significantly improving timing (66, 94) and attention functions in children with ADHD including the same tasks (22, 29–31).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [31]
Our indexed copy returns only the paper’s title and author metadata, with no Results passage. Searches for methylphenidate’s effects on attention, timing, and the same tasks found no substantive text, so the claimed improvement cannot be checked against this copy. (LLM, conf=0.77)
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Kenworthy, L. E., Bertollo, J. R., Pugliese, C. E., Candy, C., Armour, A. C., Csumitta, K. D., Reimann, G. E., Fritz, M. S., & Wallace, G. L. (2026) · Autism Research · doi:10.1002/aur.70385
- Authors
- Isfandnia, F., El Masri, S., Radua, J., & Rubia, K.
- Affiliations
- King's College London (GB)
- Corresponding author
- Rubia, Katya
- ORCID
- Rubia, Katya
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2024-07
- Volume
- 162
- Pages
- 105703
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W4396670527
- Cited by
- 36
- References
- 87
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 3
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Centres de Recerca de Catalunya
- National Institute for Health and Care Research (NIHR130077, NIHR203684)
- Department of Health and Social Care
- King's College London
- European Commission
- Deutsche Forschungsgemeinschaft (454245598)
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- NIHR Maudsley Biomedical Research Centre
- Medical Research Council
- European Regional Development Fund
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, executive function, methylphenidate, atomoxetine, stimulant medication, non-stimulant medication, chronic drug administration, reaction time, attention, inhibition, working memory
- MeSH terms
- Atomoxetine Hydrochloride, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Humans, Memory, Short-Term, Methylphenidate, Executive Function
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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