The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis

Ferdous Isfandnia; Sahid El Masri; Joaquim Radua; Katya Rubia

doi:10.1016/j.neubiorev.2024.105703

The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis

Neurosci Biobehav Rev. 2024 May 6:162:105703. doi: 10.1016/j.neubiorev.2024.105703. Online ahead of print.

Authors

Ferdous Isfandnia¹, Sahid El Masri², Joaquim Radua³, Katya Rubia⁴

Affiliations

¹ Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
² Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Department of Child & Adolescent Psychiatry, University Hospital Carl Gustav Dresden, Dresden University of Technology, Germany.
³ Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
⁴ Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Department of Child & Adolescent Psychiatry, University Hospital Carl Gustav Dresden, Dresden University of Technology, Germany. Electronic address: katya.rubia@kcl.ac.uk.

PMID: 38718988
DOI: 10.1016/j.neubiorev.2024.105703

Abstract

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.

Keywords: ADHD; Atomoxetine; Attention; Cognitive function; Executive functions; Inhibition; Methylphenidate; Non-stimulant medication; Reaction time, reaction time variability, meta-analysis; Stimulant medication; Systematic review; Working memory.

Publication types

Review