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Review
. 2018 May 9;5(5):CD012069.
doi: 10.1002/14651858.CD012069.pub2.

Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies

Ole Jakob Storebø  1 , Nadia Pedersen, Erica Ramstad, Maja Lærke Kielsholm, Signe Sofie Nielsen, Helle B Krogh, Carlos R Moreira-Maia, Frederik L Magnusson, Mathilde Holmskov, Trine Gerner, Maria Skoog, Susanne Rosendal, Camilla Groth, Donna Gillies, Kirsten Buch Rasmussen, Dorothy Gauci, Morris Zwi, Richard Kirubakaran, Sasja J Håkonsen, Lise Aagaard, Erik Simonsen, Christian Gluud
Affiliations
Review

Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies

Ole Jakob Storebø et al. Cochrane Database Syst Rev. .

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. The psychostimulant methylphenidate is the most frequently used medication to treat it. Several studies have investigated the benefits of methylphenidate, showing possible favourable effects on ADHD symptoms, but the true magnitude of the effect is unknown. Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events.

Objectives: To assess the adverse events associated with methylphenidate treatment for children and adolescents with ADHD in non-randomised studies.

Search methods: In January 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 12 other databases and two trials registers. We also checked reference lists and contacted authors and pharmaceutical companies to identify additional studies.

Selection criteria: We included non-randomised study designs. These comprised comparative and non-comparative cohort studies, patient-control studies, patient reports/series and cross-sectional studies of methylphenidate administered at any dosage or formulation. We also included methylphenidate groups from RCTs assessing methylphenidate versus other interventions for ADHD as well as data from follow-up periods in RCTs. Participants had to have an ADHD diagnosis (from the 3rd to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders or the 9th or 10th edition of theInternational Classification of Diseases, with or without comorbid diagnoses. We required that at least 75% of participants had a normal intellectual capacity (intelligence quotient of more than 70 points) and were aged below 20 years. We excluded studies that used another ADHD drug as a co-intervention.

Data collection and analysis: Fourteen review authors selected studies independently. Two review authors assessed risk of bias independently using the ROBINS-I tool for assessing risk of bias in non-randomised studies of interventions. All review authors extracted data. We defined serious adverse events according to the International Committee of Harmonization as any lethal, life-threatening or life-changing event. We considered all other adverse events to be non-serious adverse events and conducted meta-analyses of data from comparative studies. We calculated meta-analytic estimates of prevalence from non-comparative cohorts studies and synthesised data from patient reports/series qualitatively. We investigated heterogeneity by conducting subgroup analyses, and we also conducted sensitivity analyses.

Main results: We included a total of 260 studies: 7 comparative cohort studies, 6 of which compared 968 patients who were exposed to methylphenidate to 166 controls, and 1 which assessed 1224 patients that were exposed or not exposed to methylphenidate during different time periods; 4 patient-control studies (53,192 exposed to methylphenidate and 19,906 controls); 177 non-comparative cohort studies (2,207,751 participants); 2 cross-sectional studies (96 participants) and 70 patient reports/series (206 participants). Participants' ages ranged from 3 years to 20 years. Risk of bias in the included comparative studies ranged from moderate to critical, with most studies showing critical risk of bias. We evaluated all non-comparative studies at critical risk of bias. The GRADE quality rating of the evidence was very low.Primary outcomesIn the comparative studies, methylphenidate increased the risk ratio (RR) of serious adverse events (RR 1.36, 95% confidence interval (CI) 1.17 to 1.57; 2 studies, 72,005 participants); any psychotic disorder (RR 1.36, 95% CI 1.17 to 1.57; 1 study, 71,771 participants); and arrhythmia (RR 1.61, 95% CI 1.48 to 1.74; 1 study, 1224 participants) compared to no intervention.In the non-comparative cohort studies, the proportion of participants on methylphenidate experiencing any serious adverse event was 1.20% (95% CI 0.70% to 2.00%; 50 studies, 162,422 participants). Withdrawal from methylphenidate due to any serious adverse events occurred in 1.20% (95% CI 0.60% to 2.30%; 7 studies, 1173 participants) and adverse events of unknown severity led to withdrawal in 7.30% of participants (95% CI 5.30% to 10.0%; 22 studies, 3708 participants).Secondary outcomesIn the comparative studies, methylphenidate, compared to no intervention, increased the RR of insomnia and sleep problems (RR 2.58, 95% CI 1.24 to 5.34; 3 studies, 425 participants) and decreased appetite (RR 15.06, 95% CI 2.12 to 106.83; 1 study, 335 participants).With non-comparative cohort studies, the proportion of participants on methylphenidate with any non-serious adverse events was 51.2% (95% CI 41.2% to 61.1%; 49 studies, 13,978 participants). These included difficulty falling asleep, 17.9% (95% CI 14.7% to 21.6%; 82 studies, 11,507 participants); headache, 14.4% (95% CI 11.3% to 18.3%; 90 studies, 13,469 participants); abdominal pain, 10.7% (95% CI 8.60% to 13.3%; 79 studies, 11,750 participants); and decreased appetite, 31.1% (95% CI 26.5% to 36.2%; 84 studies, 11,594 participants). Withdrawal of methylphenidate due to non-serious adverse events occurred in 6.20% (95% CI 4.80% to 7.90%; 37 studies, 7142 participants), and 16.2% were withdrawn for unknown reasons (95% CI 13.0% to 19.9%; 57 studies, 8340 participants).

Authors' conclusions: Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events. It might be higher than reported here.Given the possible association between methylphenidate and the adverse events identified, it may be important to identify people who are most susceptible to adverse events. To do this we must undertake large-scale, high-quality RCTs, along with studies aimed at identifying responders and non-responders.

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Conflict of interest statement

Ole Jakob Storebø is an Associate Editor with Cochrane Developmental, Psychosocial and Learning Problems. Nadia Pedersen ‐ none known. Erica Ramstad ‐ none known. Maja Lærke Kielsholm ‐ none known. Signe Sofie Nielsen ‐ none known. Helle B Krogh ‐ none known. Carlos R Moreira‐Maia (CRMM) receives financial research support from the government agencies: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). CRMM received fees in February 2016 for the development of educational materials on excessive daytime sleepiness for Libbs. Libbs also make products for the treatment of ADHD. CRMM received travel awards from the Health Technology Assessment Institute (IATS), Universidade Federal do Rio Grande do Sul (UFRGS); and travel, accommodation, and registration support to the fourth and fifth World Congresses on ADHD from the World Federation of ADHD. Carlos is an author on Maia 2008 and declares that he was not involved in assessing the eligibility of this study, extracting data, assessing risk of bias or grading the quality of the evidence. Frederik L Magnusson ‐ none known. Mathilde Holmskov ‐ none known. Trine Gerner ‐ none known. Maria Skoog ‐ none known. Susanne Rosendal ‐ none known. Camilla Groth's (CGr) institution received funds from the Lundbeck Foundation to finance part of her PhD in the paediatric field on Tourette syndrome. CGr confirms that none of these funds were used to work on this review. Donna Gillies is an Editor with Cochrane Developmental, Psychosocial, and Learning Problems. Kirsten Buch Rasmussen ‐ none known. Dorothy Gauci ‐ none known. Morris Zwi sits on the UK Paediatric Medicines Expert Advisory Group at the Medicines and Healthcare Regulatory Agency, which considers applications regarding the licensing of paediatric medicines. Payment for MZ's attendance at this meeting goes to his NHS organisation. As a clinician working with patients who have ADHD, he prescribes methylphenidate regularly. Richard Kirubakaran is currently employed by Cochrane South Asia, funded by the Indian Council for Medical Research, India, and Effective Healthcare Research Consortium for the Department for International Development, UK. Sasja J Håkonsen ‐ none known. Lise Aagaard (LA) received travelling grants from the pharmaceutical companies Pfizer, Swedish Orphan BioVitrum and Shire. None of the travelling grants are related to this review. LA confirms that she has nothing to declare in relation to ADHD research. The Pfizer travel grants were received in 2015 and 2016 for attending the European Association of Hospital Pharmacist Annual Conferences. No activities in relation to treatment of ADHD were observed. A travel grant was received in 2015 from Swedish Orphan Biovitrum for attending the C1 Inhibitor Conference in Budapest. C1 inhibitor drugs are involved in the treatment of the rare disease hereditary angioedema. Travel grants were received in 2015 and 2016 from Shire for attending the Bradykinin Scientific Meeting in Copenhagen and Stockholm. Bradykinin mediator drugs are involved in the treatment of the rare disease hereditary angioedema. Erik Simonsen ‐ none known. Christian Gluud is Co‐ordinating Editor of Cochrane Hepato‐Biliary.

Figures

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Study flow diagram
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Proportion of participants on methylphenidate with any serious adverse events
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Proportion of participants withdrawn from methylphenidate due to serious adverse events
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Proportion of participants withdrawn from methylphenidate due to adverse events of unknown severity
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Proportion of participants on methylphenidate with any non‐serious adverse event
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Proportion of participants withdrawn from methylphenidate due to non‐serious adverse events
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Proportion of participants withdrawn from methylphenidate for unknown reasons
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Confino‐Cohen 2005 {published data only}
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Coşkun 2011 {published data only}
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Davari‐Ashtiani 2010 {published data only}
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Döpfner 2011b {published data only}
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Döpfner 2011c {published data only}
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Dubnov‐Raz 2011 {published data only}
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El‐Zein 2005 {published data only}
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Findling 2010 {published data only}
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Ghanizadeh 2008c {published data only}
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Hammerness 2009 {published data only}
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    1. Hammerness P, Biederman J, Petty C, Henin A, Moore CM. Brain biochemical effects of methylphenidate treatment using proton magnetic spectroscopy in youth with attention‐deficit hyperactivity disorder: a controlled pilot study. CNS Neuroscience and Therapeutics. P. Hammerness, Massachusetts General Hospital, 185 Alewife Brook Parkway, Suite 2000, Cambridge, MA 02138, United States. E‐mail: [email protected]: Blackwell Publishing Ltd (9600 Garsington Road, Oxford OX4 2XG, United Kingdom), 2012; Vol. 18, issue 1:34‐40. [DOI: 10.1111/j.1755-5949.2010.00226.x; PMC4084790; PUBMED: 21143432] - DOI - PMC - PubMed
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Hazell 2003 {published data only}
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Holtkamp 2002 {published data only}
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Hong 2012 {published data only}
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Hulvershorn 2012 {published data only}
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Ilgenli 2007 {published data only}
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Işeri 2007 {published data only}
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Jafarinia 2012 {published data only}
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Jensen 1999 (MTA) {published data only}
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Johnson 2013 {published data only}
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Jung 2007 {published data only}
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Karabekiroglu 2008 {published data only}
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Karaman 2010 {published data only}
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Karapinar 2014 {published data only}
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Kazanci 2015 {published data only}
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Kemner 2005 (FOCUS) {published data only}
    1. Kemner JE, Starr HL, Bowen DL, Ciccone PL, Lynch JM. Greater symptom improvement and response rates with OROS® MPH vs. atomoxetine in children with ADHD. International Journal of Neuropsychopharmacology 2004;7:S273‐4. [DOI: 10.1017/S1461145704004547] - DOI
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Khajehpiri 2014 {published data only}
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Khodadust 2012 {published data only}
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Kim 2010 {published data only}
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Kim 2011 {published data only}
    1. Kim BN, Kim YN, Cheong US, Kim JW, Hwang JW, Shin MS, et al. Switching from Methylphenidate‐Immediate Release (MPH‐IR) to Methylphenidate‐OROS (OROS‐MPH): a multi‐center, open‐label study in Korea. Clinical Psychopharmacology and Neuroscience 2011;9(1):29‐35. [DOI: 10.9758/cpn.2011.9.1.29; PMC3568652; PUBMED: 23430964] - DOI - PMC - PubMed
Kim 2014a {published data only}
    1. Kim HW, Kim SO, Shon S, Lee JS, Lee HJ, Choi JH. Effect of methylphenidate on height and weight in Korean children and adolescents with attention‐deficit/hyperactivity disorder: a retrospective chart review. Journal of Child and Adolescent Psychopharmacology 2014;24(8):448‐53. [DOI: 10.1089/cap.2014.0025; PUBMED: 25285915] - DOI - PubMed
Kim 2014b {published data only}
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Kim 2015a {published data only}
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Klein 2004 {published data only}
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Kordon 2011 {published data only}
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Kratochvil 2002 {published data only}
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Kraut 2013 {published data only}
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Lahat 2000 {published data only}
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Lakic 2012 {published data only}
    1. Lakic A, Kesic A, Dronjak D. Tics in children with attention‐deficit/hyperactivity disorder under treatment with the sustained‐release form of methylphenidate. European Neuropsychopharmacology 2012; Vol. 22, issue Suppl 2:S420. [DOI: 10.1016/S0924-977X(12)70658-2] - DOI
Lamberti 2015 {published data only}
    1. Lamberti M, Italiano D, Guerriero L, D'Amico G, Siracusano R, Ingrassia M, et al. Evaluation of acute cardiovascular effects of immediate‐release methylphenidate in children and adolescents with attention‐deficit hyperactivity disorder. Neuropsychiatric Disease and Treatment 2015;11:1169‐74. [DOI: 10.2147/NDT.S79866; PMC4431494; PUBMED: 26056451] - DOI - PMC - PubMed
Langevin 2012 {published data only}
    1. Langevin R, Ramdé J. Attention deficit hyperactivity disorder (ADHD) in children, seasonal photoperiods, nocturnal movements and diurnal agitation. Journal of the Canadian Academy of Child and Adolescent Psychiatry 2012;21(1):53‐8. [PMC3269251] - PMC - PubMed
Larrañaga‐Fragoso 2015 {published data only}
    1. Larrañaga‐Fragoso P, Noval S, Rivero JC, Boto‐de‐los‐Bueis A. The effects of methylphenidate on refraction and anterior segment parameters in children with attention deficit hyperactivity disorder. Journal of AAPOS 2015;19(4):322‐6. [DOI: 10.1016/j.jaapos.2015.04.005; PUBMED: 26235791] - DOI - PubMed
Lee 2007 {published data only}
    1. Lee SI, Hong SD, Kim S. Efficacy and tolerability of OROS methylphenidate in Korean children with AD/HD ‐ Reply. Progress in Neuro‐Psychopharmacology and Biological Psychiatry 2007; Vol. 31, issue 5:1151‐2. [DOI: 10.1016/j.pnpbp.2007.03.019] - DOI - PubMed
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Lee 2009 {published data only}
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Lee 2012 {published data only}
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Lyon 2010 {published data only}
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Maayan 2009 {published data only}
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MacDonald 2005 {published data only}
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Machado 2010 {published data only}
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    1. Maia CR. Evalution of the Exchange of Immediate Release Methylphenidate for Prolonged Release Methylphenidate in Attention Deficit/Hyperactivity Disorder [Availação da troca do metilfenidato de liberação imediata para o metilfenidato de liberação prolongada no transtorno de déficit de atenção/hiperatividade] [Masters thesis]. Rio Grande (BZ): The Federal University of Rio Grande, 2009.
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Mino 1999 {published data only}
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Mohammadi 2010 {published data only}
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Montañés‐Rada 2012 {published data only}
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Montiel‐Nava 2002 {published data only}
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Moungnoi 2011 {published data only}
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Niederhofer 2011 {published data only}
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Park 2013 {published data only}
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Perera 2010 {published data only}
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Peyre 2012a {published data only}
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Polanczyk 2007 {published data only}
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Poulton 2003 {published data only}
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Poulton 2012 {published data only}
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Ramasamy 2014 {published data only}
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Rappaport 2004 {published data only}
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Rapport 1996 {published data only}
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Rashid 2007 {published data only}
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Remschmidt 2005 {published data only}
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Sahin 2014 {published data only}
    1. Sahin S, Yuce M, Alacam H, Karabekiroglu K, Say GN, Salis O. Effect of methylphenidate treatment on appetite and levels of leptin, ghrelin, adiponectin, and brain‐derived neurotrophic factor in children and adolescents with attention deficit and hyperactivity disorder. International Journal of Psychiatry in Clinical Practice 2014;18(4):280‐7. [DOI: 10.3109/13651501.2014.940054; PUBMED: 24994482] - DOI - PubMed
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    1. Shin JY, Roughead EE, Park BJ, Pratt NL. Cardiovascular safety of methylphenidate among children and young people with attention‐deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study. BMJ 2016;353:i2550. [DOI: 10.1136/bmj.i2550] - DOI - PMC - PubMed
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Zheng 2011 {published data only}
    1. Zheng Y, Wang YF, Qin J, Wang LW, Zou LP, Jin XM, et al. Prospective, naturalistic study of open‐label OROS methylphenidate treatment in Chinese school‐aged children with attention‐deficit/hyperactivity disorder. Chinese Medical Journal 2011;124(20):3269‐74. [PUBMED: 22088519] - PubMed
Zheng 2015 {published data only}
    1. Zheng Y, Liang JM, Gao HY, Yang ZW, Jia FJ, Liang YZ, et al. An open‐label, self‐control, prospective study on cognitive function, academic performance, and tolerability of osmotic‐release oral system methylphenidate in children with attention‐deficit hyperactivity disorder. Chinese Medical Journal 2015;128(22):2988‐97. [DOI: 10.4103/0366-6999.168948; PMC4795269; PUBMED: 26608976] - DOI - PMC - PubMed

References to studies excluded from this review

Bart 2010 {published data only}
    1. Bart O, Podoly T, Bar‐Haim Y. A preliminary study on the effect of methylphenidate on motor performance in children with comorbid DCD and ADHD. Research in Developmental Disabilities 2010;31(6):1443‐7. [DOI: 10.1016/j.ridd.2010.06.014; PUBMED: 20650602] - DOI - PubMed
Beauchaine 2003 {published data only}
    1. Beauchaine TP, Gartner Joseph. A linear growth curve analysis of inpatient treatment response by conduct‐disordered, ADHD, and comorbid preadolescents. Aggressive Behavior 2003;29(5):440‐56. [DOI: 10.1002/ab.10066] - DOI
Becker 2011 {published data only}
    1. Becker A, Roessner V, Breuer D, Döpfner M, Rothenberger A. Relationship between quality of life and psychopathological profile: data from an observational study in children with ADHD. European Child and Adolescent Psychiatry 2011;20(Suppl 2):S267‐75. [DOI: 10.1007/s00787-011-0204-2; PMC3180591; PUBMED: 21901415] - DOI - PMC - PubMed
Beery 1994 {published data only}
    1. Beery SH. Behavioral Disinhibition, Anxiety, and Response to Methylphenidate and Behavior Management in Children with Attention Deficit Hyperactivity Disorder [PhD thesis]. Miami (FL): University of Miami, 1994.
Benamor 2014 {published data only}
    1. Benamor L. H‐Magnetic resonance spectroscopy study of stimulant medication effect on brain metabolites in French Canadian children with attention deficit hyperactivity disorder. Neuropsychiatric Disease and Treatment 2014;10:47‐54. [DOI: 10.2147/NDT.S52338; PMC3901735] - DOI - PMC - PubMed
Biederman 1999 {published data only}
    1. Biederman J, Wilens T, Mick E, Spencer T, Faraone SV. Pharmacotherapy of attention‐deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics 1999;104(2):e20. [PUBMED: 10429138] - PubMed
Biederman 2009 {published data only}
    1. Biederman J, Monuteaux MC, Spencer T, Wilens TE, Faraone SV. Do stimulants protect against psychiatric disorders in youth with ADHD? A 10‐year follow‐up study. Pediatrics 2009;124(1):71‐8. [DOI: 10.1542/peds.2008-3347; 10.1542/peds.2008‐3347; PUBMED: 19564285] - DOI - PMC - PubMed
Bohane 2010 {published data only}
    1. Bohane L, Young M, Rowlandson P. Medication in attention deficit hyperactivity disorder and ADHD with Autistic Spectrum Disorder (ASD). Procedia ‐ Social and Behavioral Sciences 2010;5:655‐9. [DOI: 10.1016/j.sbspro.2010.07.160] - DOI
Brossard‐Racine 2012 {published data only}
    1. Brossard‐Racine M, Shevell M, Snider L, Bélanger SA, Majnemer A. Motor skills of children newly diagnosed with Attention Deficit Hyperactivity Disorder prior to and following treatment with stimulant medication. Research in Developmental Disabilities 2012;33(6):2080‐7. [DOI: 10.1016/j.ridd.2012.06.003; PUBMED: 22796639] - DOI - PubMed
Byrne 1998 {published data only}
    1. Byrne JM, Bawden HN, DeWolfe NA, Beattie TL. Clinical assessment of psychopharmacological treatment of preschoolers with ADHD. Journal of Clinical and Experimental Neuropsychology 1998;20(5):613‐27. [DOI: 10.1076/jcen.20.5.613.1121; PUBMED: 10079039] - DOI - PubMed
Casat 1995 {published data only}
    1. Casat CD, Pearson DA, Davelaar MJ, Cherek DR, Van‐Davelaar MJ. Methylphenidate effects on a laboratory aggression measure in children with ADHD. Psychopharmacology Bulletin 1995;31(2):353‐6. [PUBMED: 7491391] - PubMed
Cavadas 2007 {published data only}
    1. Cavadas M, Pereira LD, Mattos P. Effects of methylphenidate in auditory processing evaluation of children and adolescents with attention deficit hyperactivity disorder [Efeito do metilfenidato no processamento auditivo em crianças e adolescentes com transtorno do deficit de atenção/hiperatividade]. Arquivos de Neuro‐Psiquiatria 2007;65(1):138‐43. [DOI: 10.1590/S0004-282X2007000100028; PUBMED: 17420844] - DOI - PubMed
Chambers 2012 {published data only}
    1. Chambers NA, Pascoe E, Kaplanian S, Forsyth I. Ingestion of stimulant medications does not alter bispectral index or clinical depth of anesthesia at 1 MAC sevoflurane in children. Paediatric Anaesthesia 2012;22(4):341‐4. [DOI: 10.1111/j.1460-9592.2011.03717.x; PUBMED: 21988202] - DOI - PubMed
Chavez 1999 {published data only}
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Chelonis 2010 {published data only}
    1. Chelonis JJ, Johnson TA, Ferguson SA, Kubacak B, Edwards M, Paule M. Effects of methylphenidate on motivation in children with attention‐deficit/hyperactivity disorder. Neurotoxicology and Teratology 2010;32(4):504. [DOI: 10.1016/j.ntt.2010.04.031] - DOI - PubMed
Chelonis 2011 {published data only}
    1. Chelonis JJ, Johnson TA, Ferguson SA, Berry KJ, Kubacak B, Edwards MC, et al. Effect of methylphenidate on motivation in children with attention‐deficit/hyperactivity disorder. Experimental and Clinical Psychopharmacology 2011;19(2):145‐53. [DOI: 10.1037/a0022794; PUBMED: 21463072] - DOI - PubMed
Clarke 2003 {published data only}
    1. Clarke AR, Barry RJ, McCarthy R, Selikowitz M, Clarke DC, Croft R J. Effects of stimulant medications on children with attention‐deficit/hyperactivity disorder and excessive beta activity in their EEG. Clinical Neurophysiology 2003;114(9):1729‐37. [PUBMED: 12948803] - PubMed
Conzelmann 2014 {published data only}
    1. Conzelmann A, Gerdes AB, Mucha RF, Weyers P, Lesch KP, Bähne CG, et al. Autonomic hypoactivity in boys with attention‐deficit/hyperactivity disorder and the influence of methylphenidate. World Journal of Biological Psychiatry 2014;15(1):56‐65. [DOI: 10.3109/15622975.2013.829584; PUBMED: 24410179] - DOI - PubMed
Cooper 2011 {published data only}
    1. Cooper WO. E‐mail regarding your study 'ADHD drugs and serious cardiovascular events in children and young adults'. Email to: M Holmskov 10 September 2014.
    1. Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, et al. ADHD drugs and serious cardiovascular events in children and young adults. New England Journal of Medicine 2011;365(20):1896‐904. [DOI: 10.1056/NEJMoa1110212] - DOI - PMC - PubMed
DeVito 2009 {published data only}
    1. DeVito EE, Blackwell AD, Clark L, Kent L, Dezsery AM, Turner DC, et al. Methylphenidate improves response inhibition but not reflection‐impulsivity in children with attention deficit hyperactivity disorder (ADHD). Psychopharmacology 2009;202(1‐3):531‐9. [DOI: 10.1007/s00213-008-1337-y; PMC2704617; PUBMED: 18818905] - DOI - PMC - PubMed
De Zeeuw 2012 {published data only}
    1. Zeeuw P, Mandl RC, Hulshoff Pol HE, Engeland H, Durston S. Decreased frontostriatal microstructural organization in attention deficit/hyperactivity disorder. Human Brain Mapping 2012; Vol. 33, issue 8:1941‐51. [DOI: 10.1002/hbm.21335; PUBMED: 21826757] - DOI - PMC - PubMed
Drtílková 1990 {published data only}
    1. Drtílková I, Misurec J, Náhunek K. The paradox effect of psychostimulants in the treatment of the child hyperkinetic syndrome. Activitas Nervosa Superior 1990;32(4):302‐3. [PUBMED: 1982036] - PubMed
Epstein 2010 {published data only}
    1. Epstein JN, Langberg JM, Lichtenstein PK, Altaye M, Brinkman WB, House K, et al. Attention‐deficit/hyperactivity disorder outcomes for children treated in community‐based pediatric settings. Archives of Pediatrics & Adolescent Medicine 2010;164(2):160‐5. [DOI: 10.1001/archpediatrics.2009.263; PUBMED: 20124145] - DOI - PubMed
Faraone 2007b {published data only}
    1. Faraone SV, Biederman J, Zimmerman B. An analysis of patient adherence to treatment during a 1‐year, open‐label study of OROS methylphenidate in children with ADHD. Journal of Attention Disorders 2007;11(2):157‐66. [DOI: 10.1177/1087054706295663; PUBMED: 17494833] - DOI - PubMed
Fegert 2006 {published data only}
    1. Fegert JM, Hebebrand J, Kommission Entwicklungspsychopharmakologie der drei Fachgesellschaften. Statement to questionable cardiac risks of application of stimulants [Stellungnahme zu fraglichen kardialen Risiken der Stimulanziengabe]. Zeitschrift für Kinder‐ und Jugendpsychiatrie und Psychotherapie 2006;34(4):295‐97. [DOI: 10.1024/1422-4917.34.4.295] - DOI - PubMed
Foodman 1996 {published data only}
    1. Foodman A, McPhillips K. ADD and soft signs. Journal of the American Academy of Child and Adolescent Psychiatry 1996;35(7):841‐2. [PUBMED: 8768341] - PubMed
Frank 1993 {published data only}
    1. Frank Y. Visual event related potentials after methylphenidate and sodium valproate in children with attention deficit hyperactivity disorder. Clinical EEG 1993;24(1):19‐24. [PUBMED: 8420693] - PubMed
Funk 1993 {published data only}
    1. Funk JB, Chessare JB, Weaver MT, Exley AR. Attention deficit hyperactivity disorder, creativity, and the effects of methylphenidate. Pediatrics 1993;91(4):816‐9. [PUBMED: 8464673] - PubMed
Gau 2009 {published data only}
    1. Gau SS, Chiu CD, Shang CY, Cheng AT, Soong WT. Executive function in adolescence among children with attention‐deficit/hyperactivity disorder in Taiwan. Journal of Developmental and Behavioral Pediatrics 2009;30(6):525‐34. [DOI: 10.1097/DBP.0b013e3181c21c97; PUBMED: 19884851] - DOI - PubMed
Gimpel 2005 {published data only}
    1. Gimpel GA, Collett BR, Veeder MA, Gifford JA, Sneddon P, Bushman B, et al. Effects of stimulant medication on cognitive performance of children with ADHD. Clinical Pediatrics 2005;44(5):405‐11. [DOI: 10.1177/000992280504400504; PUBMED: 15965546] - DOI - PubMed
Glenngård 2013 {published data only}
    1. Glenngård AH, Hjelmgren J, Thomsen P H, Tvedten T, Prtz C. Eliciting patient preferences for ADHD treatment using Discrete Choice Experiment in Sweden, Norway and Denmark. Journal of Mental Health Policy and Economics 2011;14(Suppl 1):S8‐9.
    1. Glenngård AH, Hjelmgren J, Thomsen PH, Tvedten T. Patient preferences and willingness‐to‐pay for ADHD treatment with stimulants using discrete choice experiment (DCE) in Sweden, Denmark and Norway. Nordic Journal of Psychiatry 2013;67(5):351‐9. [DOI: 10.3109/08039488.2012.748825; PUBMED: 23245636] - DOI - PubMed
Gormez 2012 {published data only}
    1. Gormez V, Avery B, Mann H. An additional mid‐afternoon dose of immediate release methylphenidate (MPH‐IR) with Concerta XL provides better symptom control in children and adolescents with attention deficit/hyperactivity disorder (ADHD). European Psychiatry 2012;27(Suppl 1):1. [DOI: 10.1016/S0924-9338(12)74460-7] - DOI
Gould 2009 {published data only}
    1. Gould MS, Walsh BT, Munfakh JL, Kleinman M, Duan NH, Olfson M, et al. Sudden death and use of stimulant medications in youths. American Journal of Psychiatry 2009;166(9):992‐1001. [DOI: 10.1176/appi.ajp.2009.09040472; PUBMED: 19528194] - DOI - PubMed
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    1. Kuehn BM. Stimulant use linked to sudden death in children without heart problems. JAMA: Journal of the American Medical Association 2009;302(6):613‐4. [DOI: 10.1001/jama.2009.1115; PUBMED: 19671894] - DOI - PubMed
    1. Uhl D. Stimulant therapy: sudden death cases under methylphenidate [Plötzliche Todesfälle unter Methylphenidat]. Deutsche Apotheker Zeitung 2009;26:46‐8.
Gualtieri 1985 {published data only}
    1. Gualtieri CT, Hicks RE. Neuropharmacology of methylphenidate and a neural substrate for childhood hyperactivity. Psychiatric Clinics of North America 1985;8(4):875‐92. [PUBMED: 2867534] - PubMed
Guimarães 2009 {published data only}
    1. Guimarães AP, Zeni C, Polanczyk G, Genro JP, Roman T, Rohde LA, et al. MAOA is associated with methylphenidate improvement of oppositional symptoms in boys with attention deficit hyperactivity disorder. International Journal of Neuropsychopharmacology 2009;12(5):709‐14. [DOI: 10.1017/S1461145709000212; PUBMED: 19309535] - DOI - PubMed
Gurkan 2011 {published data only}
    1. Gurkan CK, Yurumez E, Akca OF, Bilgic A, Turkoglu S, Kilic BG, et al. The effect of treatment on multiple symptom domains and quality of life in children and adolescents with ADHD: A 3‐year follow‐up study. European Child and Adolescent Psychiatry 2011;20(Suppl 1):S170. [DOI: 10.1007/s00787-011-0181-5] - DOI
Hautmann 2013 {published data only}
    1. Hautmann C, Rothenberger A, Döpfner M. An observational study of response heterogeneity in children with attention deficit hyperactivity disorder following treatment switch to modified‐release methylphenidate. BMC Psychiatry 2013;13:219. [DOI: 10.1186/1471-244X-13-219; PMC3846116; PUBMED: 24004962] - DOI - PMC - PubMed
Hawcutt 2012 {published data only}
    1. Hawcutt DB, Mainie P, Riordan A, Smyth RL, Pirmohamed M. Reported paediatric adverse drug reactions in the UK 2000‐2009. British Journal of Clinical Pharmacology 2012;73(3):437‐46. [DOI: 10.1111/j.1365-2125.2011.04113.x; PMC3370348; PUBMED: 21988288] - DOI - PMC - PubMed
Hawk 2003 {published data only}
    1. Hawk LW Jr, Yartz AR, Pelham WE Jr, Lock TM. The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention‐deficit hyperactivity disorder. Psychopharmacology 2003;165(2):118‐27. [DOI: 10.1007/s00213-002-1235-7; PUBMED: 12417963] - DOI - PubMed
Heiser 2004 {published data only}
    1. Heiser P, Frey J, Smidt J, Sommerlad C, Wehmeier PM, Hebebrand J, et al. Objective measurement of hyperactivity, impulsivity, and inattention in children with hyperkinetic disorders before and after treatment with methylphenidate. European Child and Adolescent Psychiatry 2004;13(2):100‐4. [DOI: 10.1007/s00787-004-0365-3; PUBMED: 15103535] - DOI - PubMed
Hidas 2011 {published data only}
    1. Hidas A, Noy AF, Birman N, Shapira J, Matot I, Steinberg D, et al. Oral health status, salivary flow rate and salivary quality in children, adolescents and young adults with ADHD. Archives of Oral Biology 2011; Vol. 56, issue 10:1137‐41. [DOI: 10.1016/j.archoralbio.2011.03.018; PUBMED: 21514566] - DOI - PubMed
Hood 2005 {published data only}
    1. Hood J, Baird G, Rankin PM, Isaacs E. Immediate effects of methylphenidate on cognitive attention skills of children with attention‐deficit‐hyperactivity disorder. Developmental Medicine and Child Neurology 2005;47(6):408‐14. [DOI: 10.1111/j.1469-8749.2005.tb01162.x/pdf] - DOI - PubMed
Hoza 1992 {published data only}
    1. Hoza B, Pelham WE Jr, Sams SE, Carlson C. An examination of the 'dosage' effects of both behavior therapy and methylphenidate on the classroom performance of two ADHD children. Behavior Modification 1992;16(2):164‐92. [DOI: 10.1177/01454455920162002; PUBMED: 1580892] - DOI - PubMed
Hwang 2012 {published data only}
    1. Hwang J, Kim B, Kim Y, Yoo H. Methylphenidate‐osmotic release oral delivery system reduces parenting stress in parents of children and adolescents with ADHD in Korea. European Neuropsychopharmacology 2012; Vol. 22, issue Suppl 2:S415.
Jonkman 1999 {published data only}
    1. Jonkman LM, Kemner C, Verbaten MN, Engeland H, Camfferman G, Buitelaar JK, et al. Attentional capacity, a probe ERP study: differences between children with attention‐deficit hyperactivity disorder and normal control children and effects of methylphenidate. Psychophysiology 2000;37(3):334‐46. [PUBMED: 10860411] - PubMed
    1. Jonkman LM, Kemner C, Verbaten MN, Engeland H, Kenemans JL, Camfferman G, et al. Perceptual and response interference in children with attention‐deficit hyperactivity disorder, and the effects of methylphenidate. Psychophysiology 1999;36(4):419‐29. [DOI: 10.1111/1469-8986.3640419] - DOI - PubMed
Kerdar 2007 {published data only}
    1. Kerdar MS, Scheuerpflug P, Srdinko P, Wewetzer C, Warnke A, Romanos M. Quantitative effect of treatment with methylphenidate on EEG ‐ a pilot study [EEG‐Veränderungen unter Methylphenidat ‐ eine Pilotstudie]. Z Kinder Jugendpsychiatr Psychother 2007;35(4):247‐55; quiz 255‐6. [DOI: 10.1024/1422-4917.35.4.247; PUBMED: 17970368] - DOI - PubMed
Kereszturi 2008 {published data only}
    1. Kereszturi E, Tarnok Z, Bognar E, Lakatos K, Farkas L, Gadoros J, et al. Catechol‐O‐methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. American Journal of Medical Genetics 2008;147B(8):1431‐5. [DOI: 10.1002/ajmg.b.30704; PUBMED: 18214865] - DOI - PubMed
Keulers 2007 {published data only}
    1. Keulers EH, Hendriksen JG, Feron FJ, Wassenberg R, Wuisman‐Frerker MG, Jolles J, et al. Methylphenidate improves reading performance in children with attention deficit hyperactivity disorder and comorbid dyslexia: an unblinded clinical trial. European Journal of Paediatric Neurology 2007;11(1):21‐8. [DOI: 10.1016/j.ejpn.2006.10.002; PUBMED: 17169593] - DOI - PubMed
Klein 2002 {published data only}
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Kramer 2001 {published data only}
    1. Kramer AF, Cepeda NJ, Cepeda ML. Methylphenidate effects on task‐switching performance in attention‐deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 2001;40(11):1277‐84. [DOI: 10.1097/00004583-200111000-00007; PUBMED: 11699801] - DOI - PubMed
Lajoie 2005 {published data only}
    1. Lajoie G, Anderson V, Anderson P, Tucker AR, Robertson IH, Manly T. Effects of methylphenidate on attention skills in children with attention deficit/hyperactivity disorder. Brain Impairment 2005;6(1):21‐32. [DOI: 10.1375/brim.6.1.21.65479] - DOI
Lawrence 2005 {published data only}
    1. Lawrence CA, Barry RJ, Clarke AR, Johnstone SJ, McCarthy R, Selikowitz M, et al. Methylphenidate effects in attention deficit/hyperactivity disorder: electrodermal and ERP measures during a continuous performance task. Psychopharmacology 2005;183(1):81‐91. [DOI: 10.1007/s00213-005-0144-y; PUBMED: 16160877] - DOI - PubMed
Matier 1992 {published data only}
    1. Matier K, Halperin JM, Sharma V, Newcorn JH, Sathaye N. Methylphenidate response in aggressive and nonaggressive ADHD children: distinctions on laboratory measures of symptoms. Journal of the American Academy of Child and Adolescent Psychiatry 1992;31(2):219‐25. [DOI: 10.1097/00004583-199203000-00007; PUBMED: 1564022] - DOI - PubMed
Mayes 1993 {published data only}
    1. Mayes SD, Bixler EO. Reliability of global impressions for assessing methylphenidate effects in children with attention‐deficit hyperactivity disorder. Perceptual and Motor Skills 1993;77(3 Pt 2):1215‐8. [DOI: 10.2466/pms.1993.77.3f.1215; PUBMED: 8170770] - DOI - PubMed
Miller 1994 {published data only}
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Miller 1996 {published data only}
    1. Miller DC, Kavcic V, Leslie JE. ERP changes induced by methylphenidate in boys with attention‐deficit hyperactivity disorder. Journal of Attention Disorders 1996; Vol. 1, issue 2:95‐113. [DOI: 10.1177/108705479600100203] - DOI
Miranda 2006 {published data only}
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Monden 2012a {published data only}
    1. Monden Y, Dan H, Nagashima M, Dan I, Kyutoku Y, Okamoto M, et al. Clinically‐oriented monitoring of acute effects of methylphenidate on cerebral hemodynamics in ADHD children using fNIRS. Clinical Neurophysiology 2012; Vol. 123, issue 6:1147‐57. [DOI: 10.1016/j.clinph.2011.10.006; PUBMED: 22088661] - DOI - PubMed
Monden 2012b {published data only}
    1. Monden Y, Dan H, Nagashima M, Dan I, Tsuzuki D, Kyutoku Y, et al. Right prefrontal activation as a neuro‐functional biomarker for monitoring acute effects of methylphenidate in ADHD children: an fNIRS study. NeuroImage: Clinical 2012;1(1):131‐40. [DOI: 10.1016/j.nicl.2012.10.001; PMC3757725; PUBMED: 24179746] - DOI - PMC - PubMed
Nahshoni 2012 {published data only}
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Neef 2005 {published data only}
    1. Neef NA, Bicard DF, Endo S, Coury DL, Aman MG. Evaluation of pharmacological treatment of impulsivity in children with attention deficit hyperactivity disorder. Journal of Applied Behavior Analysis 2005;38(2):135‐46. [DOI: 10.1901/jaba.2005.116-02; PMC1226151] - DOI - PMC - PubMed
Negrao 2011 {published data only}
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Nigg 1996 {published data only}
    1. Nigg JT, Swanson JM, Hinshaw SP. Covert visual spatial attention in boys with attention deficit hyperactivity disorder: lateral effects, methylphenidate response and results for parents. Neuropsychologia 1996;35(2):165‐76. [PUBMED: 9025120] - PubMed
Nikles 2005 {published data only}
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Nolan 1999 {published data only}
    1. Nolan EE, Gadow KD, Sprafkin J. Stimulant medication withdrawal during long‐term therapy in children with comorbid attention‐deficit hyperactivity disorder and chronic multiple tic disorder. Pediatrics 1999;103(4 Pt 1):730‐7. [PUBMED: 10103294] - PubMed
Ohashi 2010 {published data only}
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Orgill 1996 {published data only}
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Overcash 2005 {published data only}
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Ozdag 2004 {published data only}
    1. Ozdag MF, Yorbik O, Ulas UH, Hamamcioglu K, Vural O. Effect of methylphenidate on auditory event related potential in boys with attention deficit hyperactivity disorder. International Journal of Pediatric Otorhinolaryngology 2004;68(10):1267‐72. [DOI: 10.1016/j.ijporl.2004.04.023; PUBMED: 15364497] - DOI - PubMed
Palomino 2012 {published data only}
    1. Palomino MD, Martín‐Calero MJ, Marques G. Involvement of community pharmacists on attention‐deficit/hyperactivity disorder patients. A pilot study [Implicación del farmacéutico comunitario en la dispensación a pacientes con trastorno por déficit de atención e hiperactividad. Un estudio piloto]. Pharmaceutical Care España 2012;14(5):183‐92.
Park 2012 {published data only}
    1. Park MH, Kim JW, Yang YH, Hong SB, Park S, Kang H, et al. Regional brain perfusion before and after treatment with methylphenidate may be associated with the G1287A polymorphism of the norepinephrine transporter gene in children with attention‐deficit/hyperactivity disorder. Neuroscience Letters 2012; Vol. 514, issue 2:159‐63. [DOI: 10.1016/j.neulet.2012.02.079; PUBMED: 22405810] - DOI - PubMed
Pelham 1986 {published data only}
    1. Pelham WE, Milich R, Walker JL. Effects of continuous and partial reinforcement and methylphenidate on learning in children with Attention Deficit Disorder. Journal of Abnormal Psychology 1986;95(4):319‐25. [PUBMED: 3805493] - PubMed
Pelham 2011 {published data only}
    1. Pelham WE Jr, Waschbusch DA, Hoza B, Gnagy EM, Greiner AR, Sams SE, et al. Music and video as distractors for boys with ADHD in the classroom: comparison with controls, individual differences, and medication effects. Journal of Abnormal Child Psychology 2011; Vol. 39, issue 8:1085‐98. [DOI: 10.1007/s10802-011-9529-z; PUBMED: 21695447] - DOI - PubMed
Perera 2012 {published data only}
    1. Perera H, Jeewandara KC, Seneviratne S, Guruge C. Combined ω3 and ω6 supplementation in children with attention‐deficit hyperactivity disorder (ADHD) refractory to methylphenidate treatment: a double‐blind, placebo‐controlled study. Journal of Child Neurology 2012; Vol. 27, issue 6:747‐53. [DOI: 10.1177/0883073811435243; PUBMED: 22596014] - DOI - PubMed
Pierce 2008 {published data only}
    1. Pierce D, Dixon CM, Wigal SB, McGough JJ. Pharmacokinetics of methylphenidate transdermal system (MTS): results from a laboratory classroom study. Journal of Child and Adolescent Psychopharmacology 2008;18(4):355‐64. [DOI: 10.1089/cap.2007.0148; PUBMED: 18759645] - DOI - PubMed
Poulton 2013 {published data only}
    1. Poulton AS, Melzer E, Tait PR, Garnett SP, Cowell Chris, Baur LA, et al. Growth and pubertal development of adolescent boys on stimulant medication for attention deficit hyperactivity disorder. Medical Journal of Australia 2013;198(1):29‐32. [PUBMED: 23330767] - PubMed
Prehn‐Kristensen 2011 {published data only}
    1. Prehn‐Kristensen A, Krauel K, Hinrichs H, Fischer J, Malecki U, Schuetze H, et al. Methylphenidate does not improve interference control during a working memory task in young patients with attention‐deficit hyperactivity disorder. Brain Research 2011;1388:56‐68. [DOI: 10.1016/j.brainres.2011.02.075; PUBMED: 21385569] - DOI - PubMed
Rapport 1985 {published data only}
    1. Rapport MD, DuPaul GJ, Smith NF. Rate‐dependency and hyperactivity: methylphenidate effects on operant responding. Pharmacology, Biochemistry, and Behavior 1985;23(1):77‐83. [PUBMED: 4034622] - PubMed
Rhodes 2004 {published data only}
    1. Rhodes SM, Coghill DR, Matthews K. Methylphenidate restores visual memory, but not working memory function in attention deficit‐hyperkinetic disorder. Psychopharmacology 2004;175(3):319‐30. [DOI: 10.1007/s00213-004-1833-7; PUBMED: 15138760] - DOI - PubMed
Rhodes 2006 {published data only}
    1. Rhodes SM, Coghill DR, Matthews K. Acute neuropsychological effects of methylphenidate in stimulant drug‐naïve boys with ADHD II‐‐broader executive and non‐executive domains. Journal of Child Psychology and Psychiatry, and Allied Disciplines 2006;47(11):1184‐94. [DOI: 10.1111/j.1469-7610.2006.01633.x; PUBMED: 17076758] - DOI - PubMed
Roman 2002 {published data only}
    1. Roman T, Szobot C, Martins S, Biederman J, Rohde LA, Hutz MH. Dopamine transporter gene and response to methylphenidate in attention‐deficit/hyperactivity disorder. Pharmacogenetics 2002;12(6):497‐9. [PUBMED: 12172219] - PubMed
Rubia 2009 {published data only}
    1. Rubia K, Halari R, Cubillo AI, Taylor ET. Methylphenidate modulates inferior and orbitofrontal brain activation in ADHD during sustained attention and reward. European Neuropsychopharmacology 2009; Vol. 19, issue Suppl 3:S304‐5. [DOI: 10.1016/S0924-977X(09)70452-3] - DOI
Rubia 2009a {published data only}
    1. Rubia K, Halari R, Cubillo A, Mohammad AM, Brammer M, Taylor E. Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication‐naïve children with ADHD during a rewarded continuous performance task. Neuropharmacology 2009;57(7‐8):640‐52. [DOI: 10.1016/j.neuropharm.2009.08.013; PUBMED: 19715709] - DOI - PubMed
Rubio 2011 {published data only}
    1. Rubio B, Hernández S, Verche E, Martín R, González‐Pérez P. A pilot study: differential effects of methylphenidate‐OROS on working memory and attention functions in children with attention‐deficit/hyperactivity disorder with and without behavioural comorbidities. Attention Deficit and Hyperactivity Disorders 2011;3(1):13‐20. [DOI: 10.1007/s12402-010-0035-x; PUBMED: 21432614] - DOI - PubMed
Schecklmann 2011 {published data only}
    1. Schecklmann M, Schaldecker M, Aucktor S, Brast J, Kirchgässner K, Muhlberger A, et al. Effects of methylphenidate on olfaction and frontal and temporal brain oxygenation in children with ADHD. Journal of Psychiatric Research 2011;45(11):1463‐70. [DOI: 10.1016/j.jpsychires.2011.05.011; PUBMED: 21689828] - DOI - PubMed
Scheres 2003 {published data only}
    1. Scheres A, Oosterlaan J, Swanson J, Morein‐Zamir S, Meiran N, Schut H, et al. The effect of methylphenidate on three forms of response inhibition in boys with AD/HD. Journal of Abnormal Child Psychology 2003;31(1):105‐20. [PUBMED: 12597703] - PubMed
Scheres 2006 {published data only}
    1. Scheres A, Oosterlaan J, Sergeant JA. Speed of inhibition predicts teacher‐rated medication response in boys with attention deficit hyperactivity disorder. International Journal of Disability, Development and Education 2006;53(1):93‐109. [DOI: 10.1080/10349120500510107] - DOI
Schmiedeler 2009 {published data only}
    1. Schmiedeler S, Schwenck C, Schneider W. The mental process of negating values in children with ADHD and effects of medical treatment [Die Verarbeitung von Negationen bei Kindern mit ADHS und der Einfluss medikamentöser Behandlung]. Kindheit und Entwicklung 2009;18(3):137‐43. [DOI: 10.1026/0942-5403.18.3.137] - DOI
Shafritz 2004 {published data only}
    1. Shafritz KM, Marchione KE, Gore JC, Shaywitz SE, Shaywitz BA. The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder. American Journal of Psychiatry 2004;161(11):1990‐7. [DOI: 10.1176/appi.ajp.161.11.1990] - DOI - PubMed
Shaywitz 1982 {published data only}
    1. Shaywitz SE, Hunt RD, Jatlow P. Psychopharmacology of attention deficit disorder: pharmacokinetic, neuroendocrine, and behavioral measures following acute and chronic treatment with methylphenidate. Pediatrics 1982;69(6):688‐94. [PUBMED: 7079034] - PubMed
Sheppard 1999 {published data only}
    1. Sheppard DM, Bradshaw JL, Mattingly JB, Lee P. Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder. Journal of Neurology, Neurosurgery and Psychiatry 1999;66(1):57‐63. [PMC1736185; PUBMED: 9886453] - PMC - PubMed
Snyder 2008 {published data only}
    1. Snyder AM, Maruff P, Pietrzak RH, Cromer JR, Snyder PJ. Effect of treatment with stimulant medication on nonverbal executive function and visuomotor speed in children with attention deficit/hyperactivity disorder (ADHD). Child Neuropsychology 2008;14(3):211‐26. [DOI: 10.1080/09297040701220005; PUBMED: 17852127] - DOI - PubMed
Solanto 1989 {published data only}
    1. Solanto MV, Wender EH. Does methylphenidate constrict cognitive functioning?. Journal of the American Academy of Child and Adolescent Psychiatry 1989;28(6):897‐902. [DOI: 10.1097/00004583-198911000-00014; PUBMED: 2808260] - DOI - PubMed
Spivak 2001 {published data only}
    1. Spivak B, Vered Y, Yoran‐Hegesh R, Graft E, Averbuch E, Vinokurow S, et al. The influence of three months of methylphenidate treatment on platelet‐poor plasma biogenic amine levels in boys with attention deficit hyperactivity disorder. Human Psychopharmacology 2001;16(4):333‐7. [DOI: 10.1002/hup.298; PUBMED: 12404569] - DOI - PubMed
Stein 1999 {published data only}
    1. Jerome L. Can methylphenidate facilitate sleep in children with attention deficit hyperactivity disorder?. Journal of Child and Adolescent Psychopharmacology 2001;11(1):109. [DOI: 10.1089/104454601750143564; PUBMED: 11322740] - DOI - PubMed
    1. Stein MA. Unravelling sleep problems in treated and untreated children with ADHD. Journal of Child and Adolescent Psychopharmacology 1999;9(3):157‐68. [DOI: 10.1089/cap.1999.9.157; PUBMED: 10521009] - DOI - PubMed
Syrigou‐Papavasiliou 1988 {published data only}
    1. Syrigou‐Papavasiliou A, Lycaki H, LeWitt PA, Verma NP, Spivak D, Chayasirisobhon S. Dose‐response effects of chronic methylphenidate administration on late event‐related potentials in attention deficit disorder. Clinical Electroencephalography 1988;19(3):129‐33. [DOI: 10.1177/155005948801900306] - DOI - PubMed
Tabori‐Kraft 2007 {published data only}
    1. Tabori‐Kraft J, Sørensen M, Kærgaard M, Dalsgaard S, Thomsen PH. Is OPTAx[TM] useful for monitoring the effect of stimulants on hyperactivity and inattention?. European Child and Adolescent Psychiatry 2007;16(5):347‐51. [DOI: 10.1007/s00787-006-0571-2] - DOI - PubMed
Tamm 2007 {published data only}
    1. Tamm L, Carlson CL. Task demands interact with the single and combined effects of medication and contingencies on children with ADHD. Journal of Attention Disorders 2007;10(4):372‐80. [DOI: 10.1177/1087054706289946; PUBMED: 17449836] - DOI - PubMed
Tillery 1998 {published data only}
    1. Tillery KL. A Double‐Blind Study of the Central Auditory Processing and Auditory Continuous Test Performances of Children with Attention Deficit Hyperactivity Disorder and Central Auditory Processing Disorder Under Ritalin and Placebo Conditions [PhD thesis]. Buffalo (NY): University of Buffalo, The State University of New York, 1998.
Trenque 2009 {published data only}
    1. Taam MA, Boissieu P, Dukic S, Herlem E, Trenque T. Hallucinations: a case/noncase study in the French Pharmacovigilance Database. Pharmacoepidemiology and Drug Safety 2013;22(Suppl 1):315‐6. [DOI: 10.1002/pds.3512] - DOI
    1. Trenque T. Methylphenidate off‐label use. Drug Safety 2012;35(10):891.
    1. Trenque T, Herlem E, Germain M L. Spontaneous reporting with methylphenidate: insufficient data. Drug Safety 2009;32(10):983. [DOI: 10.2165/11316660-000000000-00000] - DOI
    1. Trenque T, Maura G, Herlem E. Spontaneous reporting with methylphenidate: off‐label use in growth?. Fundamental and Clinical Pharmacology. 2012; Vol. 26:105.
Vance 1999 {published data only}
    1. Vance AL, Luk ES, Costin J, Tonge BJ, Pantelis C. Attention deficit hyperactivity disorder: anxiety phenomena in children treated with psychostimulant medication for 6 months or more. Australian and New Zealand Journal of Psychiatry 1999;33(3):399‐406. [DOI: 10.1046/j.1440-1614.1999.00575.x] - DOI - PubMed
Van der Meere 2009 {published data only}
    1. Meere JJ, Shalev RS, Borger N, Wiersema JR. Methylphenidate, interstimulus interval, and reaction time performance of children with attention deficit/hyperactivity disorder: a pilot study. Child Neuropsychology 2009;15(6):554‐66. [DOI: 10.1080/09297040902758803; PUBMED: 19296298] - DOI - PubMed
Van der Oord 2012 {published data only}
    1. Oord S, Geurts HM, Prins PJ, Emmelkamp PM, Oosterlaan J. Prepotent response inhibition predicts treatment outcome in attention deficit/hyperactivity disorder. Child Neuropsychology 2012;18(1):50‐61. [DOI: 10.1080/09297049.2011.559159; PUBMED: 21819279] - DOI - PubMed
Vickers 2002 {published data only}
    1. Vickers JN, Rodrigues ST, Brown LN. Gaze pursuit and arm control of adolescent males diagnosed with attention deficit hyperactivity disorder (ADHD) and normal controls: evidence of a dissociation in processing visual information of short and long duration. Journal of Sports Sciences 2002;20(3):201‐16. [DOI: 10.1080/026404102317284763] - DOI - PubMed
Vogt 2011 {published data only}
    1. Vogt C, Williams T. Early identification of stimulant treatment responders, partial responders and non‐responders using objective measures in children and adolescents with hyperkinetic disorder. Child and Adolescent Mental Health 2011; Vol. 16, issue 3:144‐9. [DOI: 10.1111/j.1475-3588.2010.00593.x] - DOI - PubMed
Winterstein 2007 {published data only}
    1. Winterstein AG, Gerhard T, Shuster J, Johnson M, Zito JM, Saidi A. Cardiac safety of central nervous system stimulants in children and adolescents with attention‐deficit/hyperactivity disorder. Pediatrics 2007;120(6):e1494‐501. [DOI: 10.1542/peds.2007-0675; PUBMED: 18055666] - DOI - PubMed
Winterstein 2012 {published data only}
    1. Winterstein AG, Gerhard T, Kubilis P, Saidi A, Linden S, Crystal S, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ 2012; Vol. 345:e4627. [DOI: 10.1136/bmj.e4627] - DOI - PMC - PubMed
Wong 2012 {published data only}
    1. Wong CG, Stevens MC. The effects of stimulant medication on working memory functional connectivity in attention‐deficit/hyperactivity disorder. Biological Psychiatry 2012; Vol. 71, issue 5:458‐66. [DOI: 10.1016/j.biopsych.2011.11.011; PMC4120250; PUBMED: 22209640] - DOI - PMC - PubMed
Yeh 2012 {published data only}
    1. Yeh CB, Huang WS, Lo MC, Chang CJ, Ma KH, Shyu JF. The rCBF brain mapping in adolescent ADHD comorbid developmental coordination disorder and its changes after MPH challenging. European Journal of Paediatric Neurology 2012; Vol. 16, issue 6:613‐8. [DOI: 10.1016/j.ejpn.2012.02.007; PUBMED: 22417719] - DOI - PubMed
Zachor 2006 {published data only}
    1. Zachor DA, Roberts AW, Hodgens JB, Isaacs JS, Merrick J. Effects of long‐term psychostimulant medication on growth of children with ADHD. Research in Developmental Disabilities 2006;27(2):162‐74. [DOI: 10.1016/j.ridd.2004.12.004; PUBMED: 15955659] - DOI - PubMed
Zalsman 2003 {published data only}
    1. Zalsman G, Pumeranz O, Peretz G, Ben‐Dor DH, Dekel S, Horesh N, et al. Attention patterns in children with attention deficit disorder with or without hyperactivity. Scientific World Journal 2003;3:1093‐107. [DOI: 10.1100/tsw.2003.94; PUBMED: 14625396] - DOI - PMC - PubMed
Zang 2005 {published data only}
    1. Zang YF, Jin Z, Weng XC, Zhang L, Zeng YW, Yang L, et al. Functional MRI in attention‐deficit hyperactivity disorder: evidence for hypofrontality. Brain and Development 2005;27(8):544‐50. [DOI: 10.1016/j.braindev.2004.11.009; PUBMED: 15876503] - DOI - PubMed

References to studies awaiting assessment

Arnold‐Von 2000 {published data only}
    1. Arnold‐von Saher RA, Boer F, Burggraaf J. The clinical use of a double‐blind placebo‐controlled trial with methylphenidate: advantages and limitations [Pleidooi voor een dubbelblinde proefbehandeling met methylfenidaat in de dagelijkse klinische praktijk van ADHD bij kinderen]. Tijdschrift voor Psychiatrie 2000;42(11):837‐44.
Dalsgaard 2011 {published data only}
    1. Dalsgaard S, Kvist AP, Leckman JF, Nielsen HS, Simonsen M. Cardiovascular safety of stimulants in children with attention‐deficit/hyperactivity disorder: a nationwide prospective cohort study. Journal of Child and Adolescent Psychopharmacology 2014;24(6):1‐9. [DOI: 10.1089/cap.2014.0020; PMC4137345; PUBMED: 24956171] - DOI - PMC - PubMed
    1. Dalsgaard S, Leckman JF, Mortensen PB, Nielsen HS, Simonsen M. Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study. Lancet Psychiatry 2015;2(8):702‐9. [DOI: 10.1016/S2215-0366(15)00271-0; PUBMED: 26249301] - DOI - PubMed
    1. Dalsgaard S, Nielsen HS, Simonsen M. Long‐term cardiac adverse effects of ADHD medication in children and adolescents: a nationwide register based follow‐up study. European Child and Adolescent Psychiatry 2011;20(Suppl 1):S107. [DOI: 10.1007/s00787-011-0181-5] - DOI
Flapper 1989 {published data only}
    1. Flapper BC, Koopman HM, Heltzel A. Methylphenidate a stimulant in treatment of children with minimal brain dysfunction. Tijdschrift voor Kindergeneeskunde 1989;57(1):14‐20. - PubMed
Husár 2006 {published data only}
    1. Husár M, Zerhau P. Priapism in childhood ‐ case report of 14‐year‐old boy [Priapismus v dĕtsékm veku ‐ kazuistika 14 letého chlapce]. Rozhledy V Chirurgii 2006;85(7):329‐30. [PUBMED: 17044274] - PubMed
Ince 2015 {published data only}
    1. Ince E, Algedik P, Demirdogen ES, Emul M, Demir T. The relationship between acute dyskinesia with a single dose of methylphenidate and recent risperidone discontinuation in a child with attention‐deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology 2015;25(4):378‐9. [DOI: 10.1089/cap.2014.0148; PUBMED: 25920038] - DOI - PubMed
Ishizaki 2001 {published data only}
    1. Ishizaki A, Sugama M. Methylphenidate therapy in 141 patients with hyperkinetic disorder or with pervasive developmental disorder and hyperkinesia. No To Hattatsu 2001;33(4):323‐8. [PUBMED: 11494575] - PubMed
Laezer 2015 {published data only}
    1. Laezer KL. Effectiveness of psychoanalytic psychotherapy and behavioral therapy treatment in children with attention deficit hyperactivity disorder and oppositional defiant disorder. Journal of Infant, Child, and Adolescent Psychotherapy 2015, 2015;14(2):111‐28. [DOI: 10.1080/15289168.2015.1014991] - DOI
Mulas 2014 {published data only}
    1. Mulas F, Roca P, Ros‐Cervera G, Gandía‐Benetó R, Ortiz‐Sánchez P. Pharmacological management of attention deficit hyperactivity disorder with methylphenidate and atomoxetine within a context of epilepsy [Manejo farmacológico del trastorno por déficit de atención/hiperactividad con metilfenidato y atomoxetina en un contexto de epilepsia]. Revista de Neurologia 2014;58(Suppl 1):S34‐9. [PUBMED: 25252667] - PubMed
Ptáček 2008 {published data only}
    1. Ptáček R, Kuželová H, Paclt I, Žukov I. Effect of medication on anthropometric characteristic of ADHD children [Vliv medikace na antropometrické charakteristiky dětí s ADHD]. Ceska a Slovenska Psychiatrie 2008;104(8):415‐9.
    1. Ptáček R, Kuželová H, Paclt I, Žukov I, Fischer S. Developmental changes in children with ADHD and effecto [sic] of medication on growth [Vyvojove zmeny u deti s ADHD a vliv medikace na rust]. Psychiatrie 2009;13(Suppl):104‐5.
Radziuk 2015 {published data only}
    1. Radziuk AL, Kieling RR, Santos K, Rotert R, Bastos F, Palmini AL. Methylphenidate improves the quality of life of children and adolescents with ADHD and difficult‐to‐treat epilepsies. Epilepsy and Behavior 2015;46:215‐20. [DOI: 10.1016/j.yebeh.2015.02.019; PUBMED: 25940104] - DOI - PubMed
Socanski 2015 {published data only}
    1. Socanski D, Aurlien D, Herigstad A, Thomsen PH, Larsen TK. Attention deficit/hyperactivity disorder and interictal epileptiform discharges: it is safe to use methylphenidate?. Seizure 2015; Vol. 25:80‐3. [DOI: 10.1016/j.seizure.2015.01.002; PUBMED: 25645642] - DOI - PubMed
Sugama 2009 {published data only}
    1. Sugama M, Ishizaki A. Clinical assessment of the effect of switch from immediate‐release to extended‐release methylphenidate in 181 patients with isolated attention deficit/hyperactivity disorder (AD/HD) or AD/HD associated with pervasive developmental disorder. No to Hattatsu 2009;41(6):436‐41. [PUBMED: 19928542] - PubMed
TOSCA 2011 {published data only}
    1. Polypharmacy in treating severe childhood aggression. Brown University Child and Adolescent Psychopharmacology Update 2012;14(1):1‐4. [DOI: 10.1002/cpu.20155] - DOI
    1. Aman MG, Bukstein OG, Gadow KD, Arnold LE, Molina BS, McNamara NK, et al. What does risperidone add to parent training and stimulant for severe aggression in child attention‐deficit/hyperactivity disorder?. Journal of the American Academy of Child and Adolescent Psychiatry 2014;53(1):47‐60. [DOI: 10.1016/j.jaac.2013.09.022; PMC3984501; PUBMED: 24342385] - DOI - PMC - PubMed
    1. Farmer CA, Arnold LE, Bukstein OG, Findling RL, Gadow KD, Li Xi, et al. The treatment of severe child aggression (TOSCA) study: design challenges. Child and Adolescent Psychiatry and Mental Health 2011;5(1):36. [DOI: 10.1186/1753-2000-5-36; PMC3231878; PUBMED: 22074813] - DOI - PMC - PubMed
Waldon 2016 {published data only}
    1. Gendron M, Rusak B, Rajda M, Corkum PV. Assessing the impact of methylphenidate on sleep in children with ADHD using polysomnography and actigraphy. Sleep 2012;35:A374.
    1. Waldon J, Begum E, Gendron M, Rusak B, Andreou P, Rajda M, et al. Concordance of actigraphy with polysomnography in children with and without attention‐deficit/hyperactivity disorder. Journal of Sleep Research 2016;25(5):524‐33. [PUBMED: 27140929] - PubMed
Yusufoglu 2014 {published data only}
    1. Yusufoglu C, Sonkaya AR, Taymur I. Henoch‐Schönlein Purpura with attention deficit hyperactivity disorder. Klinik Psikofarmakoloji Bülteni [Bulletin of Clinical Psychopharmacology] 2014;24(Suppl 1):S158‐S159.

References to ongoing studies

Beau 2009 {published data only}
    1. Beau R, Douglas I, Smeeth L, Evans SJ. Spontaneous report safety signals profile and comparative Bayesian analysis of ADHD medication in children in the UK. Pharmacoepidemiology and Drug Safety 2009;18(S1):S208‐9. [DOI: 10.1002/pds.1806] - DOI
Bottelier 2014 {published data only}
    1. Bottelier MA, Schouw ML, Klomp A, Tamminga HG, Schrantee AG, Bouziane C, et al. The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design. BMC Psychiatry 2014;14(48):2‐12. [DOI: 10.1186/1471-244X-14-48] - DOI - PMC - PubMed
Dahlgren 2012 {published data only}
    1. Dahlgren J, Wentz E. Overweight and obese children with diagnosed attention deficit hyperactivity disorder have a favourable weight loss with methylphenidate ‐ one year data. Obesity Facts 2012; Vol. 5, issue Suppl 1:208.
Díez‐Suárez 2015 {published data only}
    1. Castro‐Manglano P, Vallejo‐Valdivielso M, Díez‐Suárez A, Figueroa‐Quintana A. Factors that may predict a good response to pharmacological treatment. European Child and Adolescent Psychiatry 2015;24(Suppl 1):S74‐5. [DOI: 10.1007/s00787-015-0714-4] - DOI
    1. Díez‐Suárez A, Vallejo‐Valdivielso M, Mendez J, Castro‐Manglano P. Long term effects of medication for ADHD in weight and height in children and adolescents. European Child and Adolescent Psychiatry 2015;24(Suppl 1):S74. [DOI: 10.1007/s00787-015-0714-4] - DOI
    1. Díez‐Suárez A, Vallejo‐Valdivieso M, Marín‐Méndez J, Castro‐Manglano P, Soutullo C. Weight, height and body mass index in patients with adhd treated with methylphenidate. European Child and Adolescent Psychiatry 2015;24(Suppl 1):S175. [DOI: 10.1007/s00787-015-0714-4] - DOI - PubMed
    1. Vallejo‐Valdivielso M, Castro‐Manglano P, Díez‐Suárez A, Marín‐Méndez J, Figueroa‐Quintana A. Clinical and neurocognitive predictive factors for good response to methylphenidate treatment in a ADHD sample in Spain: a naturalistic follow‐up study. European Child and Adolescent Psychiatry 2015;24(Suppl 1):S137. [DOI: 10.1007/s00787-015-0714-4] - DOI
Djurkovic‐Lazic 2009 {published data only}
    1. Djurkovic‐Lazic J, Lazic B, Milojevic N, Djuric D. School children with ADHD ‐ effects of once‐daily OROS methylphenidate treatment ADHD symptoms included improvement academic functioning. European Psychiatry 2009;24(Suppl 1):S396. [DOI: 10.1016/S0924-9338(09)70629-7] - DOI
Gau 2010 {published data only}
    1. Gau CS, Chen CF, Gau SS. The influence of using methylphenidate on the coming up of psychiatric disorders in children with ADHD. Pharmacoepidemiology and Drug Safety 2010;19(Suppl 1):S152‐3. [DOI: 10.1002/pds.2019] - DOI
Houmann 2011 {published data only}
    1. Houmann T, Skovgaard AM, Rasmussen HB. Individualised methylphenidate therapy based on pharmacogenomics: focus on carboxylesterase1 (CES1). European Child and Adolescent Psychiatry 2011;20(Suppl 1):S120. [DOI: 10.1007/s00787-011-0181-5] - DOI
Yook 2012 {published data only}
    1. Yook KH, Kim YW, Suh HS. Obesity is associated with non‐response to prolonged‐release methylphenidate treatment in ADHD. European Neuropsychopharmacology 2012;22(Suppl 2):S415‐6. [DOI: 10.1016/S0924-977X(12)70651-X] - DOI

Additional references

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References to other published versions of this review

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