Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study

Simple item page
dc.check.date2023-09-20en
dc.check.infoAccess to this article is restricted until 6 months after publication by request of the publisher.en
dc.contributor.authorMan, Kenneth K. C.en
dc.contributor.authorHäge, Alexanderen
dc.contributor.authorBanaschewski, Tobiasen
dc.contributor.authorInglis, Sarah K.en
dc.contributor.authorBuitelaar, Janen
dc.contributor.authorCarucci, Saraen
dc.contributor.authorDanckaerts, Marinaen
dc.contributor.authorDittmann, Ralf W.en
dc.contributor.authorFalissard, Brunoen
dc.contributor.authorGaras, Peteren
dc.contributor.authorHollis, Chrisen
dc.contributor.authorKonrad, Kerstinen
dc.contributor.authorKovshoff, Hannaen
dc.contributor.authorLiddle, Elizabethen
dc.contributor.authorMcCarthy, Suzanneen
dc.contributor.authorNeubert, Antjeen
dc.contributor.authorNagy, Peteren
dc.contributor.authorRosenthal, Ericen
dc.contributor.authorSonuga-Barke, Edmund J. S.en
dc.contributor.authorZuddas, Alessandroen
dc.contributor.authorWong, Ian C. K.en
dc.contributor.authorCoghill, Daviden
dc.contributor.authorCouper, Tessaen
dc.contributor.authorMasi, Gabrieleen
dc.contributor.authorGagliano, Antonellaen
dc.contributor.authorLamberti, Marcoen
dc.contributor.authorMaschietto, Dinoen
dc.contributor.authorCostantino, Antonellaen
dc.contributor.authorMorosini, Paolaen
dc.contributor.authorFazzi, Maria Elisaen
dc.contributor.authorOehler, Klaus-Ulrichen
dc.contributor.authorPitzer, Martinaen
dc.contributor.authorFegert, Jörgen
dc.contributor.authorHäßler, Franken
dc.contributor.authorRenner, Tobiasen
dc.contributor.authorHärtling, Fabianen
dc.contributor.authorRomanos, Marcelen
dc.contributor.authorAlfred, Adamen
dc.contributor.authorRoessner, Veiten
dc.contributor.authorWallitza, Susanneen
dc.contributor.authorUebel-von Sandersleben, Henriken
dc.contributor.funderSeventh Framework Programmeen
dc.date.accessioned2023-04-26T14:22:18Z
dc.date.available2023-04-26T14:22:18Z
dc.date.issued2023-03-20en
dc.description.abstractBackground: Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents. Methods: We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6–17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (<6) were eligible for inclusion. Participants were excluded if they had previously taken any ADHD medications but remained eligible if they had previously taken or were currently taking other psychotropic drugs. The primary outcome was height velocity (height velocity SD score; estimated from at least two consecutive height measurements, and normalised with reference to the mean and SD of a population of the same age and sex). Findings: Between Feb 01, 2012, and Jan 31, 2016, 1410 participants were enrolled (756 in methylphenidate group, 391 in no-methylphenidate group, and 263 in control group). 1070 (76·3%) participants were male, 332 (23·7%) were female, and for eight gender was unknown. The average age for the cohort was 9·28 years (SD 2·78; IQR 7–11). 1312 (93·0%) of 1410 participants were White. The methylphenidate and no-methylphenidate groups differed in ADHD symptom severity and other characteristics. After controlling for the effects of these variables using propensity scores, there was little evidence of an effect on growth (24 months height velocity SD score difference –0·07 (95% CI –0·18 to 0·04; p=0·20) or increased risk of psychiatric or neurological adverse events in the methylphenidate group compared with the no-methylphenidate group. Pulse rate and systolic and diastolic blood pressure were higher in the methylphenidate group compared with the no-methylphenidate group after 24 months of treatment. No serious adverse events were reported during the study. Interpretation: Our results suggest that long-term treatment with methylphenidate for 2 years is safe. There was no evidence to support the hypothesis that methylphenidate treatment leads to reductions in growth. Methylphenidate-related pulse and blood pressure changes, although relatively small, require regular monitoring.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMan, K. K., Häge, A., Banaschewski, T., Inglis, S. K., Buitelaar, J., Carucci, S., Danckaerts, M., Dittmann, R. W., Falissard, B., Garas, P. and Hollis, C., Konrad, K., Kovshoff, H., Liddle, E., McCarthy, S., Neubert, A., Nagy, P., Rosenthal, E., Sonuga-Barke, E. J. S., Zuddas, A., Wong, I. C. K. and Coghill, D. (2023) 'Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study', The Lancet Psychiatry, 10(5), pp.323-333. doi: 10.1016/s2215-0366(23)00042-1en
dc.identifier.doi10.1016/s2215-0366(23)00042-1en
dc.identifier.eissn2215-0374en
dc.identifier.endpage333en
dc.identifier.issn2215-0366en
dc.identifier.issued5en
dc.identifier.journaltitleThe Lancet Psychiatryen
dc.identifier.startpage323en
dc.identifier.urihttps://hdl.handle.net/10468/14406
dc.identifier.volume10en
dc.language.isoenen
dc.publisherElsevier Inc.en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/260576/EU/Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects/ADDUCEen
dc.rights© 2023, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectADHDen
dc.subjectADDUCEen
dc.subjectMethylphenidateen
dc.titleLong-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) studyen
dc.typeArticle (peer-reviewed)en
oaire.citation.issue5en
oaire.citation.volume10en
Files
Original bundle
Now showing 1 - 5 of 7
Thumbnail Image
Name:
ADDUCE_paper_lancet_psychiat_20230131_v2.pdf
Size:
415.55 KB
Format:
Adobe Portable Document Format
Description:
Accepted Version
Download
Thumbnail Image
Name:
ADDUCE_paper_lancet_psychiat_20230131_v2.docx
Size:
176.3 KB
Format:
Microsoft Word XML
Description:
Author's original accepted version
Thumbnail Image
Name:
Table 1 BASELINE DEMOGRAPHICS_20230131.docx
Size:
22.38 KB
Format:
Microsoft Word XML
Description:
Table 1
Download
Thumbnail Image
Name:
Table 2 LONGITUDINAL BETWEEN GROUP ANALYSIS PART A_v2.docx
Size:
21.77 KB
Format:
Microsoft Word XML
Description:
Table 2
Download
Thumbnail Image
Name:
Table 3 LONGITUDINAL BETWEEN GROUP ANALYSIS PART B_v2.docx
Size:
26.8 KB
Format:
Microsoft Word XML
Description:
Table 3
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Pharmacy - Journal Articles