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
N1 - Funding Information:
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 .
Publisher Copyright:
© 2021 The Authors
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - attention-deficit disorder with hyperactivity
KW - drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85119935560&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2021.08.023
DO - 10.1016/j.jaac.2021.08.023
M3 - Article
C2 - 34534624
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
SN - 0890-8567
ER -