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Cited by 209Attention Deficit Hyperactivity DisorderBehavioral and Psychological StudiesPharmaceutical studies and practices

The DOI matches its Crossref record; 75 of the 77 references it cites were found in a registry or an index.

Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

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Storebø, Ole Jakob, Krogh, Helle B, Ramstad, Erica, Moreira-Maia, Carlos R, Holmskov, Mathilde, Skoog, Maria, Nilausen, Trine Danvad, Magnusson, Frederik L, Zwi, Morris, Gillies, Donna, Rosendal, Susanne, Groth, Camilla, Rasmussen, Kirsten Buch, Gauci, Dorothy, Kirubakaran, Richard, Forsbøl, Bente, Simonsen, Erik, Gluud, Christian·2015·BMJ
DOI 10.1136/bmj.h5203PMC PMC4659414
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Abstract

STUDY QUESTION: Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? METHODS: Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate with placebo or no intervention in children and adolescents with ADHD. Meta-analyses and trial sequential analyses (TSA) were conducted. Quality was assessed using GRADE. Teachers, parents, and observers rated ADHD symptoms and general behaviour. STUDY ANSWER AND LIMITATIONS: The analyses included 38 parallel group trials (n=5111, median treatment duration 49 days) and 147 crossover trials (n=7134, 14 days). The average age across all studies was 9.7 years. The analysis suggested a beneficial effect of methylphenidate on teacher rated symptoms in 19 parallel group trials (standardised mean difference (SMD) -0.77, n=1698), corresponding to a mean difference of -9.6 points on the ADHD rating scale. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio 0.98, nine trials, n=1532; TSA adjusted intervention effect RR 0.91). Methylphenidate was associated with an increased risk of non-serious adverse events (1.29, 21 trials, n=3132; TSA adjusted RR 1.29). Teacher rated general behaviour seemed to improve with methylphenidate (SMD -0.87, five trials, n=668) A change of 7 points on the child health questionnaire (CHQ) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a mean difference of 8.0 points on the CHQ (range 0-100 points), which suggests that methylphenidate may improve parent reported quality of life (SMD 0.61, three trials, n=514). 96.8% of trials were considered high risk of bias trials according to the Cochrane guidelines. All outcomes were assessed very low quality according to GRADE. WHAT THIS STUDY ADDS: The results suggest that among children and adolescents with a diagnosis of ADHD, methylphenidate may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life. However, given the risk of bias in the included studies, and the very low quality of outcomes, the magnitude of the effects is uncertain. Methylphenidate is associated with an increased risk of non-serious but not serious adverse events. FUNDING, COMPETING INTERESTS, DATA SHARING: Region Zealand Research Foundation and Copenhagen Trial Unit. Competing interests are given in the full paper on bmj.com. Full data are available in the version of this review published in The Cochrane Library.

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Crossref · 10.1136/bmj.h5203

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Figures

Fig 1 Flow of studies through review
Fig 1 Flow of studies through reviewCC BY-NC · PubMed Central
Fig 2 Teacher rated symptoms of attention-deficit/hyperactivity disorder in parallel group trials.
Fig 2 Teacher rated symptoms of attention-deficit/hyperactivity disorder in parallel group trials.CC BY-NC · PubMed Central
Fig 3 Serious adverse events in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26
Fig 3 Serious adverse events in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26CC BY-NC · PubMed Central
Fig 4 Trial sequential analysis on total number of serious adverse events. DARIS=diversity adjusted required information size; RRR=relative risk reduction
Fig 4 Trial sequential analysis on total number of serious adverse events. DARIS=diversity adjusted required information size; RRR=relative risk reductionCC BY-NC · PubMed Central
Fig 5 Non-serious adverse events in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26
Fig 5 Non-serious adverse events in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26CC BY-NC · PubMed Central
Fig 6 Trial sequential analysis on total number of non-serious adverse events. DARIS=diversity adjusted required information size; RRR=relative risk reduction
Fig 6 Trial sequential analysis on total number of non-serious adverse events. DARIS=diversity adjusted required information size; RRR=relative risk reductionCC BY-NC · PubMed Central
Fig 7 Teacher rated general behaviour in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26
Fig 7 Teacher rated general behaviour in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26CC BY-NC · PubMed Central
Fig 8 Quality of life in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26
Fig 8 Quality of life in parallel group trials. Green=low risk of bias; yellow=uncertain risk of bias; red=high risk of bias. See Cochrane review for details of references26CC BY-NC · PubMed Central

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Research works printed but not linked: 2

  1. [27]Storebø O, Pedersen N, Krogh H, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents—assessment of harms in observational studies. Cochrane Database Syst Rev 2015; (In press). PMC6494554 29744873
  2. [59]Gluud C, Nikolova D, Klingenberg SL. Cochrane Hepato-Biliary About the Cochrane Collaboration (Cochrane Review Groups (CRGs). Cochrane Rev Groups 2015;1(Art.No:LIVER). www.cochranelibrary.com/about/cochrane-review-groups.html.

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Metadata

Authors
Storebø, O. J., Krogh, H. B., Ramstad, E., Moreira-Maia, C. R., Holmskov, M., Skoog, M., Nilausen, T. D., Magnusson, F. L., Zwi, M., Gillies, D., Rosendal, S., Groth, C., Rasmussen, K. B., Gauci, D., Kirubakaran, R., Forsbøl, B., Simonsen, E., & Gluud, C.
Affiliations
  • University of Southern Denmark (DK)
  • Region Zealand (DK)
  • Copenhagen University Hospital (DK)
  • Whittington Hospital (GB)
  • Western Sydney Local Health District (AU)
  • Capital Region of Denmark (DK)
  • Herlev Hospital (DK)
  • Ministry for Health (MT)
  • Christian Medical College, Vellore (IN)
  • University of Copenhagen (DK)
Corresponding author
Storebø, Ole Jakob
ORCID
Venue
BMJ
Publisher
BMJ
Published
2015-11-25
Volume
351
Pages
h5203
ISSN
1756-1833 (ISSN-L)
DOI
10.1136/bmj.h5203
PMC
PMC4659414
OpenAlex
W2179260900
Cited by
209
References
77
Citations by year
2026: 8 · 2025: 8 · 2024: 11 · 2023: 14 · 2022: 17 · 2021: 24 · 2020: 16 · 2019: 18 · 2018: 25 · 2017: 36 · 2016: 28 · 2015: 4
FWCI
4.27
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
  • OAR@UM (University of Malta) (submittedVersion, other-oa)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc)
Funders
  • Gentofte Hospital
  • Syddansk Universitet
  • Region Sjælland
  • Copenhagen Trial Unit, Centre for Clinical Intervention Research
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
methylphenidate, attention deficit hyperactivity disorder, children, adolescents, ADHD symptoms, quality of life, adverse events, stimulant medication, teacher ratings, parent ratings, trial sequential analysis, risk of bias, quality of evidence, minimal clinically important difference, Child Health Questionnaire
MeSH terms
Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Drug Administration Schedule, Humans, Methylphenidate, Quality of Life, Randomized Controlled Trials as Topic, Treatment Outcome, Cross-Over Studies

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