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

Karen Vertessen; Marjolein Luman; Anouck Staff; Pierre Bet; Ralph de Vries; Jos Twisk; Jaap Oosterlaan

doi:10.1016/j.jaac.2021.08.023

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

Karen Vertessen, Marjolein Luman, Anouck Staff, Pierre Bet, Ralph de Vries, Jos Twisk, Jaap Oosterlaan

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

OBJECTIVE: Neurocognitive deficits are at the heart of explanatory models of ADHD and lead to significant impairments in daily life. Determine dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigate 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 (5-18 years) diagnosed with ADHD. Effect sizes (SMD) were calculated for different neurocognitive functions (baseline speed, variability in responding, non-executive 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 three MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose) and high dose (0.61-1.00 mg/kg/dose).

RESULTS: Thirty-one studies fulfilled inclusion criteria comprising 804 children with ADHD. MPH 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, non-executive 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 for MPH were found on any of the investigated functions.

CONCLUSION: MPH is 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 highlights the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.

Original language	English
Pages (from-to)	626-646
Journal	Journal of the American Academy of Child and Adolescent Psychiatry
Volume	61
Issue number	5
Early online date	11 Sept 2021
DOIs	https://doi.org/10.1016/j.jaac.2021.08.023
Publication status	Published - May 2022

Funding

This manuscript is part of the project ‘Reduce and optimize methylphenidate use in children and adolescents with ADHD’, project number 3119 funded by Innovatiefonds Zorgverzekeraars .

Funders	Funder number
Innovatiefonds Zorgverzekeraars

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaac.2021.08.023

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@article{3627905746de489bafbe1a8fcab38450,

title = "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 ADHD and lead to significant impairments in daily life. Determine dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigate 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 (5-18 years) diagnosed with ADHD. Effect sizes (SMD) were calculated for different neurocognitive functions (baseline speed, variability in responding, non-executive 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 three MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose) and high dose (0.61-1.00 mg/kg/dose).RESULTS: Thirty-one studies fulfilled inclusion criteria comprising 804 children with ADHD. MPH 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, non-executive 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 for MPH were found on any of the investigated functions.CONCLUSION: MPH is 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 highlights the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.",

author = "Karen Vertessen and Marjolein Luman and Anouck Staff and Pierre Bet and {de Vries}, Ralph and Jos Twisk and Jaap Oosterlaan",

year = "2022",

month = may,

doi = "10.1016/j.jaac.2021.08.023",

language = "English",

volume = "61",

pages = "626--646",

journal = "Journal of the American Academy of Child and Adolescent Psychiatry",

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number = "5",

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Vertessen, K , Luman, M , Staff, A, Bet, P, de Vries, R, Twisk, J & Oosterlaan, J 2022, 'Meta-analysis: Dose-dependent Effects of Methylphenidate on Neurocognitive Functioning in Children With Attention-Deficit/Hyperactivity Disorder', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 61, no. 5, pp. 626-646. https://doi.org/10.1016/j.jaac.2021.08.023

Meta-analysis: Dose-dependent Effects of Methylphenidate on Neurocognitive Functioning in Children With Attention-Deficit/Hyperactivity Disorder. / Vertessen, Karen ; Luman, Marjolein ; Staff, Anouck et al.
In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 61, No. 5, 05.2022, p. 626-646.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Meta-analysis

T2 - Dose-dependent Effects of Methylphenidate on Neurocognitive Functioning in Children With Attention-Deficit/Hyperactivity Disorder

AU - Vertessen, Karen

AU - Luman, Marjolein

AU - Staff, Anouck

AU - Bet, Pierre

AU - de Vries, Ralph

AU - Twisk, Jos

AU - Oosterlaan, Jaap

PY - 2022/5

Y1 - 2022/5

N2 - OBJECTIVE: Neurocognitive deficits are at the heart of explanatory models of ADHD and lead to significant impairments in daily life. Determine dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigate 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 (5-18 years) diagnosed with ADHD. Effect sizes (SMD) were calculated for different neurocognitive functions (baseline speed, variability in responding, non-executive 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 three MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose) and high dose (0.61-1.00 mg/kg/dose).RESULTS: Thirty-one studies fulfilled inclusion criteria comprising 804 children with ADHD. MPH 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, non-executive 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 for MPH were found on any of the investigated functions.CONCLUSION: MPH is 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 highlights the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.

AB - OBJECTIVE: Neurocognitive deficits are at the heart of explanatory models of ADHD and lead to significant impairments in daily life. Determine dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigate 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 (5-18 years) diagnosed with ADHD. Effect sizes (SMD) were calculated for different neurocognitive functions (baseline speed, variability in responding, non-executive 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 three MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose) and high dose (0.61-1.00 mg/kg/dose).RESULTS: Thirty-one studies fulfilled inclusion criteria comprising 804 children with ADHD. MPH 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, non-executive 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 for MPH were found on any of the investigated functions.CONCLUSION: MPH is 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 highlights the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.

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DO - 10.1016/j.jaac.2021.08.023

M3 - Article

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SN - 0890-8567

VL - 61

SP - 626

EP - 646

JO - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

IS - 5

ER -

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

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