Effects of Methylphenidate on Cognitive Functions in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Evidence from a Systematic Review and a Meta-Analysis

doi:10.1016/j.biopsych.2013.10.005

Biological Psychiatry

Volume 76, Issue 8, 15 October 2014, Pages 603-615

https://doi.org/10.1016/j.biopsych.2013.10.005 Get rights and content

Background

Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of neuropsychological impairments. The relationship between these neuropsychological deficits and the defining symptoms of ADHD seems more complex than originally thought. Methylphenidate (MPH) is an effective treatment for ADHD symptoms, but its impact on cognition is less clearly understood.

Methods

With a common systematic search strategy and a rigorous coding and data extraction strategy across domains, we searched electronic databases to identify published placebo controlled trials that compared MPH and placebo on executive and nonexecutive memory, reaction time, reaction time variability and response inhibition in children and adolescents (5–18 years) with a formal diagnosis of ADHD.

Results

Sixty studies were included in the review, of which 36 contained sufficient data for meta-analysis. Methylphenidate was superior to placebo in all five meta-analyses: executive memory, standardized mean difference (SMD) .26, 95% confidence interval (CI): −.39 to −.13; non-executive memory, SMD .60, 95% CI: −.79 to −.41; reaction time, SMD .24, 95% CI: −.33 to −.15; reaction time variability, SMD .62, 95% CI: −.90 to −.34; response inhibition, SMD .41, 95% CI: −.55 to −.27.

Conclusions

These data support the potentially important effects of MPH on various aspects of cognition known to be associated with ADHD. Consideration should be given to adding cognitive outcomes to the assessment of treatment outcome in ADHD, considering the complexity of the relationship between ADHD symptoms and cognition.

Section snippets

Methods and Materials

A systematic literature search was conducted to identify published studies that investigated the effects of MPH on different cognitive domains (see trial registry information after Acknowledgments).

Results

A combined PRISMA flow chart describing study selection is included in Figure S1 in Supplement 1. A full reference list for studies considered is included in Supplement 1. Sixty studies met all inclusion criteria, although 94 of the full text articles reviewed did not. The main reasons for non-inclusion were: design limitations (e.g. cohort studies, pre-post design, quasi experimental designs with matched controls); sample characteristics (no clear ADHD diagnosis or presence of exclusionary

Discussion

This is the first comprehensive systematic review and meta-analysis comparing the effects of MPH and placebo on cognitive functioning in children and adolescents with ADHD. Our hypotheses that MPH would be superior to placebo and improve executive and non-executive memory, reaction time, reaction time variability, and response inhibition were all supported by the data. These are important findings in the context of the mixed results reported across individual studies and the risk that these can

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Archival ReportEffects of Methylphenidate on Cognitive Functions in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Evidence from a Systematic Review and a Meta-Analysis

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

Results

Discussion

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Neuropsychologia

J Neurosci Methods

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Behav Brain Res

J Am Acad Child Adolesc Psychiatry

Clin Psychol Rev

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

Arch Clin Neuropsychol

Biol Psychiatry

Biol Psychiatry

Neuropharmacology

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Behav Brain Res

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Neuropsychologia

J Am Acad Child Adolesc Psychiatry

Int J Psychophysiol

Neuropsychopharmacology

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Neuropsychologia

Biol Psychol

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Int J Psychophysiol

Psychiatry Res

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

Attention-deficit/hyperactivity disorder and behavioral inhibition: A meta-analytic review of the stop-signal paradigm

J Abnorm Child Psychol

A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: Deficient inhibitory motor control?

J Abnorm Psychol

Neuropsychological functioning in stimulant-naive boys with hyperkinetic disorder

Psychol Med

Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children

Psychol Med

Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD

Psychol Bull

A comprehensive investigation of memory impairment in attention deficit hyperactivity disorder and oppositional defiant disorder

J Child Psychol Psychiatry

Psychological mechanisms in hyperactivity: I. Response inhibition deficit, working memory impairment, delay aversion, or something else?

J Child Psychol Psychiatry

Hyperactivity and delay aversion—II. The effect of self versus externally imposed stimulus presentation periods on memory

J Child Psychol Psychiatry

Hyperactivity and delay aversion—I. The effect of delay on choice

J Child Psychol Psychiatry

Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD

Proc Natl Acad Sci U S A

Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes

Nat Rev Neurosci

Whither causal models in the neuroscience of ADHD?

Dev Sci

Archival Report
Effects of Methylphenidate on Cognitive Functions in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Evidence from a Systematic Review and a Meta-Analysis