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Clinical response to a single-dose methylphenidate challenge is indicative of treatment response at two months in adults with ADHD
School of Psychology, University of Southampton, Southampton, UK; Centre for Innovation in Mental Health, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Hampshire and Isle of Wight Healthcare NHS Foundation Trust, Southampton, UK.
Institut d'Investigacions Biomediques August Pi i Sunyer, CIBERSAM, Instituto de Salud Carlos III, University of Barcelona, Barcelona, Spain.
School of Psychology, University of Southampton, Southampton, UK.
Örebro University, School of Medical Sciences. Centre for Innovation in Mental Health, University of Southampton, Southampton, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .ORCID iD: 0000-0002-4811-2330
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2025 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 15, no 1, article id 368Article in journal (Refereed) Published
Abstract [en]

Stimulants such as methylphenidate (MPH) are the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Although stimulants are effective at a group level, individual response varies, which advocates for tailored treatment approaches. Prior studies suggested that neurobiological measures following a single dose of stimulants are indicative of longer-term clinical response. To expand these findings, we tested whether an association between acute and longer-term treatment response can also be identified using measures commonly used in clinic. Sixty adults with ADHD completed clinico-neuropsychological measures, including the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) and the Quantitative behavior (Qb) test, following a single dose of MPH (20 mg) and placebo. These measures were repeated after two-month MPH treatment to ascertain response. We tested associations between single-dose and longer-term response using univariate and multivariable (Lasso) regression approaches. We also ran correlations between predicted and true outcome measures. Univariate regressions showed significant associations between single-dose and two-month improvement in BAARS hyperactivity/impulsivity and Qb scores (all p < 0.001 but Qb activity, p = 0.006). Multivariable models including acute response and baseline clinicodemographic measures yielded significant correlations between predicted and actual values for all BAARS-IV and Qb scores at follow-up, except for BAARS inattention and Qb activity. Most had large/very large effect size (up to r = 0.69). These findings suggest that specific clinico-neuropsychological changes following a single dose of MPH may be indicative of longer-term treatment response, especially when combined with pre-treatment clinico-demographic characteristics. Once validated in larger and more heterogeneous samples, these results may support more informed and individualized treatment approaches for ADHD.

Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 15, no 1, article id 368
National Category
Psychiatry Neurosciences
Identifiers
URN: urn:nbn:se:oru:diva-124240DOI: 10.1038/s41398-025-03557-3ISI: 001589121900033PubMedID: 41053032OAI: oai:DiVA.org:oru-124240DiVA, id: diva2:2004263
Funder
EU, Horizon 2020
Note

Funding Agencies:

This work was funded by Shire (project IST-ALB-000217, recipient DM) and included support from the NIHR Maudsley Biomedical Research Centre. Further, the results leading to this work have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, AUTISM SPEAKS, Autistica, and the Simons Foundation Autism Research Initiative. Any views expressed are those of the authors and not necessarily those of the funders (IHI-JU2). 

Available from: 2025-10-07 Created: 2025-10-07 Last updated: 2025-10-20Bibliographically approved

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