Evidence map›Paper›PMID 27487479›Full record

Trial reportJAMA psychiatry2016

Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial.

Anouk Schrantee, Hyke G H Tamminga, Cheima Bouziane, Marco A Bottelier, Esther E Bron, Henk-Jan M M Mutsaerts, Aeilko H Zwinderman, Inge R Groote, Serge A R B Rombouts, Ramon J L Lindauer and 8 more

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JAMA psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 6 pooled it
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 6 syntheses or guidelines pooled it, 72 citations in OpenAlex.

  1. Effect of amphetamines on blood pressure.The Cochrane database of systematic reviews · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 3 countries.

Anouk SchranteeDepartment of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands2Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands3Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands.
Hyke G H TammingaDepartment of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands4d'Arc (Dutch Autism and Attention-Deficit/Hyperactivity Disorder Research Center), Department of Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands.
Cheima BouzianeDepartment of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands2Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Marco A BottelierDepartment of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands5Department of Child and Adolescent Psychiatry, Triversum, Alkmaar, the Netherlands.
Esther E BronBiomedical Imaging Group Rotterdam, Department of Medical Informatics, Erasmus Medical Center, Rotterdam, the Netherlands7Biomedical Imaging Group Rotterdam, Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
Henk-Jan M M MutsaertsDepartment of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands2Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Aeilko H ZwindermanDepartment of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Inge R GrooteInstitute of Psychology, Department of Social Sciences, University of Oslo, Oslo, Norway.
Serge A R B RomboutsInstitute of Psychology, Leiden University, Leiden, the Netherlands11Department of Radiology, Leids Universitair Medisch Centrum, Leiden, the Netherlands.
Ramon J L LindauerDepartment of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands13De Bascule Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
Stefan KleinBiomedical Imaging Group Rotterdam, Department of Medical Informatics, Erasmus Medical Center, Rotterdam, the Netherlands.
Wiro J NiessenBiomedical Imaging Group Rotterdam, Department of Medical Informatics, Erasmus Medical Center, Rotterdam, the Netherlands14Department of Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands.
Brent C OpmeerClinical Research Unit, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Frits BoerDepartment of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands13De Bascule Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
Paul J LucassenSwammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.
Susan L AndersenDepartment of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts.
Hilde M Geurtsd'Arc (Dutch Autism and Attention-Deficit/Hyperactivity Disorder Research Center), Department of Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands.
Liesbeth RenemanDepartment of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands2Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands3Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands.
Academic Medical Center · NLUniversity of Amsterdam · NLDelft University of Technology · NLErasmus University Rotterdam · NLLeiden University Medical Center · NLMcLean Hospital · USNetherlands Institute for Neuroscience · NLUniversity of Oslo · NO

Funding

Early Drug Exposure and Drug Reward MechanismsR01DA015403 · NIDA · MC LEAN HOSPITAL (BELMONT, MA) · PI ANDERSEN, SUSAN L · 2003 to 2014
$2.6M
Developmental Mechanisms Underlying Risk Behaviors and Their TreatmentR01MH091114 · NIMH · MCLEAN HOSPITAL · PI ANDERSEN, SUSAN L, SONNTAG, KAI CHRISTIAN · 2011 to 2015
$1.8M
Sensitive periods, development, and substance abuseR01DA026485 · NIDA · MCLEAN HOSPITAL · PI ANDERSEN, SUSAN L · 2011 to 2015
$1.8M
NIDA NIH HHS R01 DA015403NIDA NIH HHS R01 DA026485NIMH NIH HHS R01 MH091114
6 · The paper itself

Abstract

importanceAlthough numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system.

objectivesTo determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function. DESIGN, SETTING, AND

participantsA randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment-naive status.

interventionsTreatment with either methylphenidate or a matched placebo for 16 weeks. MAIN OUTCOMES AND MEASURES: Change in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses.

resultsAmong 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03). CONCLUSIONS AND RELEVANCE: We confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up.

trial registrationidentifier: NL34509.000.10 and trialregister.nl identifier: NTR3103.

Indexed as

AdultAge FactorsAttention Deficit Disorder with HyperactivityBrainChildCorpus StriatumDopamineDouble-Blind MethodGyrus CinguliHumansLong-Term CareMagnetic Resonance ImagingMaleMethylphenidateNerve NetReceptors, DopamineDopamineMethylphenidateReceptors, Dopamine

Identifiers

PMID27487479
PMCPMC5267166
OpenAlexW2484812056

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.