Meta-analysis: Dose-Dependent Effects of Methylphenidate on Neurocognitive Functioning in Children With Attention-Deficit/Hyperactivity Disorder.

Abstract

OBJECTIVE:

Neurocognitive deficits are at the heart of explanatory models of attention-deficit/hyperactivity disorder (ADHD), and lead to significant impairments in daily life. Determining the dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigating possible impairing effects of high doses is therefore important.

METHOD:

Placebo-controlled trials were included that investigated MPH dosing effects on neurocognitive functions in children and adolescents (aged 5-18 years) diagnosed with ADHD. Effect sizes (standardized mean differences [SMDs]) were calculated for different neurocognitive functions (baseline speed, variability in responding, nonexecutive memory and executive memory, inhibitory control, and cognitive flexibility) and, if available, for ADHD symptoms. Meta-regression analysis were used to investigate linear effects of dose (mg/kg/dose), and separate meta-analyses compared SMDs for 3 MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose), and high (0.61-1.00 mg/kg/dose).

RESULTS:

A total of 31 studies fulfilled inclusion criteria, comprising 804 children with ADHD. Methylphenidate had beneficial effects on all neurocognitive functions (d = 0.20-0.73). Significant linear dosing effects were found for ADHD symptoms and lower-order neurocognitive functions (baseline speed, variability in responding, nonexecutive memory), with greater enhancement of functioning with increasing dose. No dosing effects were found for higher-order neurocognitive functions (executive memory, inhibitory control, and cognitive flexibility). No detrimental effects of MPH were found on any of the investigated functions.

CONCLUSION:

Methylphenidate was superior to placebo in improving ADHD symptoms and a broad range of neurocognitive functions; however, effects sizes regarding the effects of dose vary substantially between functions. Our data highlight the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.

• Authors: Karen Vertessen, Marjolein Luman, Anouck Staff, Pierre Bet, Ralph de Vries, Jos Twisk, Jaap Oosterlaan
• Journal: Journal of the American Academy of Child and Adolescent Psychiatry (J Am Acad Child Adolesc Psychiatry) Vol. 61 Issue 5 Pg. 626-646 (05 2022) ISSN: 1527-5418 [Electronic] United States
• PMID: 34534624 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Central Nervous System Stimulants
• Methylphenidate

Topics

• Adolescent
• Attention Deficit Disorder with Hyperactivity (drug therapy)
• Central Nervous System Stimulants (therapeutic use)
• Child
• Humans
• Methylphenidate (therapeutic use)
• Treatment Outcome